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Sample records for encephalitis virus veev

  1. Venezuelan Equine Encephalitis Viruses (VEEV) in Argentina: Serological Evidence of Human Infection

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    Pisano, María Belén; Oria, Griselda; Beskow, Geraldine; Aguilar, Javier; Konigheim, Brenda; Cacace, María Luisa; Aguirre, Luis; Stein, Marina; Contigiani, Marta Silvia

    2013-01-01

    Venezuelan equine encephalitis viruses (VEEV) are responsible for human diseases in the Americas, producing severe or mild illness with symptoms indistinguishable from dengue and other arboviral diseases. For this reason, many cases remain without certain diagnosis. Seroprevalence studies for VEEV subtypes IAB, ID, IF (Mosso das Pedras virus; MDPV), IV (Pixuna virus; PIXV) and VI (Rio Negro virus; RNV) were conducted in persons from Northern provinces of Argentina: Salta, Chaco and Corrientes, using plaque reduction neutralization test (PRNT). RNV was detected in all studied provinces. Chaco presented the highest prevalence of this virus (14.1%). Antibodies against VEEV IAB and -for the first time- against MDPV and PIXV were also detected in Chaco province. In Corrientes, seroprevalence against RNV was 1.3% in the pediatric population, indicating recent infections. In Salta, this was the first investigation of VEEV members, and antibodies against RNV and PIXV were detected. These results provide evidence of circulation of many VEE viruses in Northern Argentina, showing that surveillance of these infectious agents should be intensified. PMID:24349588

  2. Venezuelan equine encephalitis viruses (VEEV in Argentina: serological evidence of human infection.

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    María Belén Pisano

    Full Text Available Venezuelan equine encephalitis viruses (VEEV are responsible for human diseases in the Americas, producing severe or mild illness with symptoms indistinguishable from dengue and other arboviral diseases. For this reason, many cases remain without certain diagnosis. Seroprevalence studies for VEEV subtypes IAB, ID, IF (Mosso das Pedras virus; MDPV, IV (Pixuna virus; PIXV and VI (Rio Negro virus; RNV were conducted in persons from Northern provinces of Argentina: Salta, Chaco and Corrientes, using plaque reduction neutralization test (PRNT. RNV was detected in all studied provinces. Chaco presented the highest prevalence of this virus (14.1%. Antibodies against VEEV IAB and -for the first time- against MDPV and PIXV were also detected in Chaco province. In Corrientes, seroprevalence against RNV was 1.3% in the pediatric population, indicating recent infections. In Salta, this was the first investigation of VEEV members, and antibodies against RNV and PIXV were detected. These results provide evidence of circulation of many VEE viruses in Northern Argentina, showing that surveillance of these infectious agents should be intensified.

  3. Venezuelan equine encephalitis virus infection causes modulation of inflammatory and immune response genes in mouse brain

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    Sharma, Anuj; Bhattacharya, Bhaskar; Puri, Raj K; Maheshwari, Radha K

    2008-01-01

    Abstract Background Neurovirulent Venezuelan equine encephalitis virus (VEEV) causes lethal encephalitis in equines and is transmitted to humans by mosquitoes. VEEV is highly infectious when transmitted by aerosol and has been developed as a bio-warfare agent, making it an important pathogen to study from a military and civilian standpoint. Molecular mechanisms of VEE pathogenesis are poorly understood. To study these, the gene expression profile of VEEV infected mouse brains was investigated...

  4. Venezuelan Equine Encephalitis Virus Activity in the Gulf Coast Region of Mexico, 2003–2010

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    Adams, A. Paige; Navarro-Lopez, Roberto; Ramirez-Aguilar, Francisco J.; Lopez-Gonzalez, Irene; Leal, Grace; Flores-Mayorga, Jose M.; Travassos da Rosa, Amelia P. A.; Saxton-Shaw, Kali D.; Singh, Amber J.; Borland, Erin M.; Powers, Ann M.; Tesh, Robert B.; Weaver, Scott C.; Estrada-Franco, Jose G.

    2012-01-01

    Venezuelan equine encephalitis virus (VEEV) has been the causative agent for sporadic epidemics and equine epizootics throughout the Americas since the 1930s. In 1969, an outbreak of Venezuelan equine encephalitis (VEE) spread rapidly from Guatemala and through the Gulf Coast region of Mexico, reaching Texas in 1971. Since this outbreak, there have been very few studies to determine the northward extent of endemic VEEV in this region. This study reports the findings of serologic surveillance in the Gulf Coast region of Mexico from 2003–2010. Phylogenetic analysis was also performed on viral isolates from this region to determine whether there have been substantial genetic changes in VEEV since the 1960s. Based on the findings of this study, the Gulf Coast lineage of subtype IE VEEV continues to actively circulate in this region of Mexico and appears to be responsible for infection of humans and animals throughout this region, including the northern State of Tamaulipas, which borders Texas. PMID:23133685

  5. Candidate Vectors and Rodent Hosts of Venezuelan Equine Encephalitis Virus, Chiapas, 2006–2007

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    Deardorff, Eleanor R.; Estrada-Franco, Jose G.; Freier, Jerome E.; Navarro-Lopez, Roberto; Da Rosa, Amelia Travassos; Tesh, Robert B.; Weaver, Scott C.

    2011-01-01

    Enzootic Venezuelan equine encephalitis virus (VEEV) has been known to occur in Mexico since the 1960s. The first natural equine epizootic was recognized in Chiapas in 1993 and since then, numerous studies have characterized the etiologic strains, including reverse genetic studies that incriminated a specific mutation that enhanced infection of epizootic mosquito vectors. The aim of this study was to determine the mosquito and rodent species involved in enzootic maintenance of subtype IE VEEV in coastal Chiapas. A longitudinal study was conducted over a year to discern which species and habitats could be associated with VEEV circulation. Antibody was rarely detected in mammals and virus was not isolated from mosquitoes. Additionally, Culex (Melanoconion) taeniopus populations were found to be spatially related to high levels of human and bovine seroprevalence. These mosquito populations were concentrated in areas that appear to represent foci of stable, enzootic VEEV circulation. PMID:22144461

  6. Discovery of a novel compound with anti-venezuelan equine encephalitis virus activity that targets the nonstructural protein 2.

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    Dong-Hoon Chung

    2014-06-01

    Full Text Available Alphaviruses present serious health threats as emerging and re-emerging viruses. Venezuelan equine encephalitis virus (VEEV, a New World alphavirus, can cause encephalitis in humans and horses, but there are no therapeutics for treatment. To date, compounds reported as anti-VEEV or anti-alphavirus inhibitors have shown moderate activity. To discover new classes of anti-VEEV inhibitors with novel viral targets, we used a high-throughput screen based on the measurement of cell protection from live VEEV TC-83-induced cytopathic effect to screen a 340,000 compound library. Of those, we identified five novel anti-VEEV compounds and chose a quinazolinone compound, CID15997213 (IC50 = 0.84 µM, for further characterization. The antiviral effect of CID15997213 was alphavirus-specific, inhibiting VEEV and Western equine encephalitis virus, but not Eastern equine encephalitis virus. In vitro assays confirmed inhibition of viral RNA, protein, and progeny synthesis. No antiviral activity was detected against a select group of RNA viruses. We found mutations conferring the resistance to the compound in the N-terminal domain of nsP2 and confirmed the target residues using a reverse genetic approach. Time of addition studies showed that the compound inhibits the middle stage of replication when viral genome replication is most active. In mice, the compound showed complete protection from lethal VEEV disease at 50 mg/kg/day. Collectively, these results reveal a potent anti-VEEV compound that uniquely targets the viral nsP2 N-terminal domain. While the function of nsP2 has yet to be characterized, our studies suggest that the protein might play a critical role in viral replication, and further, may represent an innovative opportunity to develop therapeutic interventions for alphavirus infection.

  7. Discovery of a novel compound with anti-venezuelan equine encephalitis virus activity that targets the nonstructural protein 2.

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    Chung, Dong-Hoon; Jonsson, Colleen B; Tower, Nichole A; Chu, Yong-Kyu; Sahin, Ergin; Golden, Jennifer E; Noah, James W; Schroeder, Chad E; Sotsky, Julie B; Sosa, Melinda I; Cramer, Daniel E; McKellip, Sara N; Rasmussen, Lynn; White, E Lucile; Schmaljohn, Connie S; Julander, Justin G; Smith, Jeffrey M; Filone, Claire Marie; Connor, John H; Sakurai, Yasuteru; Davey, Robert A

    2014-06-01

    Alphaviruses present serious health threats as emerging and re-emerging viruses. Venezuelan equine encephalitis virus (VEEV), a New World alphavirus, can cause encephalitis in humans and horses, but there are no therapeutics for treatment. To date, compounds reported as anti-VEEV or anti-alphavirus inhibitors have shown moderate activity. To discover new classes of anti-VEEV inhibitors with novel viral targets, we used a high-throughput screen based on the measurement of cell protection from live VEEV TC-83-induced cytopathic effect to screen a 340,000 compound library. Of those, we identified five novel anti-VEEV compounds and chose a quinazolinone compound, CID15997213 (IC50 = 0.84 µM), for further characterization. The antiviral effect of CID15997213 was alphavirus-specific, inhibiting VEEV and Western equine encephalitis virus, but not Eastern equine encephalitis virus. In vitro assays confirmed inhibition of viral RNA, protein, and progeny synthesis. No antiviral activity was detected against a select group of RNA viruses. We found mutations conferring the resistance to the compound in the N-terminal domain of nsP2 and confirmed the target residues using a reverse genetic approach. Time of addition studies showed that the compound inhibits the middle stage of replication when viral genome replication is most active. In mice, the compound showed complete protection from lethal VEEV disease at 50 mg/kg/day. Collectively, these results reveal a potent anti-VEEV compound that uniquely targets the viral nsP2 N-terminal domain. While the function of nsP2 has yet to be characterized, our studies suggest that the protein might play a critical role in viral replication, and further, may represent an innovative opportunity to develop therapeutic interventions for alphavirus infection.

  8. Role of adhesion molecules and inflammation in Venezuelan equine encephalitis virus infected mouse brain

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    Honnold Shelley P

    2011-04-01

    Full Text Available Abstract Background Neuroinvasion of Venezuelan equine encephalitis virus (VEEV and subsequent initiation of inflammation in the brain plays a crucial role in the outcome of VEEV infection in mice. Adhesion molecules expressed on microvascular endothelial cells in the brain have been implicated in the modulation of the blood brain barrier (BBB and inflammation in brain but their role in VEEV pathogenesis is not very well understood. In this study, we evaluated the expression of extracellular matrix and adhesion molecules genes in the brain of VEEV infected mice. Findings Several cell to cell adhesion molecules and extracellular matrix protein genes such as ICAM-1, VCAM-1, CD44, Cadherins, integrins, MMPs and Timp1 were differentially regulated post-VEEV infection. ICAM-1 knock-out (IKO mice infected with VEEV had markedly reduced inflammation in the brain and demonstrated a delay in the onset of clinical symptoms of disease. A differential regulation of inflammatory genes was observed in the IKO mice brain compared to their WT counterparts. Conclusions These results improve our present understanding of VEEV induced inflammation in mouse brain.

  9. The ubiquitin proteasome system plays a role in venezuelan equine encephalitis virus infection.

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    Moushimi Amaya

    Full Text Available Many viruses have been implicated in utilizing or modulating the Ubiquitin Proteasome System (UPS to enhance viral multiplication and/or to sustain a persistent infection. The mosquito-borne Venezuelan equine encephalitis virus (VEEV belongs to the Togaviridae family and is an important biodefense pathogen and select agent. There are currently no approved vaccines or therapies for VEEV infections; therefore, it is imperative to identify novel targets for therapeutic development. We hypothesized that a functional UPS is required for efficient VEEV multiplication. We have shown that at non-toxic concentrations Bortezomib, a FDA-approved inhibitor of the proteasome, proved to be a potent inhibitor of VEEV multiplication in the human astrocytoma cell line U87MG. Bortezomib inhibited the virulent Trinidad donkey (TrD strain and the attenuated TC-83 strain of VEEV. Additional studies with virulent strains of Eastern equine encephalitis virus (EEEV and Western equine encephalitis virus (WEEV demonstrated that Bortezomib is a broad spectrum inhibitor of the New World alphaviruses. Time-of-addition assays showed that Bortezomib was an effective inhibitor of viral multiplication even when the drug was introduced many hours post exposure to the virus. Mass spectrometry analyses indicated that the VEEV capsid protein is ubiquitinated in infected cells, which was validated by confocal microscopy and immunoprecipitation assays. Subsequent studies revealed that capsid is ubiquitinated on K48 during early stages of infection which was affected by Bortezomib treatment. This study will aid future investigations in identifying host proteins as potential broad spectrum therapeutic targets for treating alphavirus infections.

  10. Testosterone correlates with Venezuelan equine encephalitis virus infection in macaques

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    Koterski James

    2006-03-01

    Full Text Available Abstract Here we briefly report testosterone and cytokine responses to Venezuelan equine encephalitis virus (VEEV in macaques which were used as part of a larger study conducted by the Department of Defense to better characterize pathological responses to aerosolized VEEV in non-human primates. Serial samples were collected and analyzed for testosterone and cytokines prior to and during infection in 8 captive male macaques. Infected animals exhibited a febrile response with few significant changes in cytokine levels. Baseline testosterone levels were positively associated with viremia following exposure and were significantly higher than levels obtained during infection. Such findings suggest that disease-induced androgen suppression is a reasonable area for future study. Decreased androgen levels during physiological perturbations may function, in part, to prevent immunosuppression by high testosterone levels and to prevent the use of energetic resources for metabolically-expensive anabolic functions.

  11. Eastern Equine Encephalitis Virus

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    Borucki, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2010-08-05

    Eastern equine encephalitis virus (EEEV) is a mosquito-borne virus capable of causing large outbreaks of encephalitis in humans and horses. In North America, EEEV infection has a very high mortality rate in humans, and survivors often suffer severe neurological sequelae. Interestingly, EEEV infections from South American isolates are generally subclinical. Although EEEV is divided into two antigenic varieties and four lineages, only eleven isolates have been sequenced and eight of these are from the North American variety (Lineage I). Most sequenced strains were collected from mosquitoes and only one human isolate has been sequenced. EEEV isolates exist from a variety of hosts, vectors, years, and geographical locations and efforts should focus on sequencing strains that represent this diversity.

  12. Novel inhibitors targeting Venezuelan equine encephalitis virus capsid protein identified using In Silico Structure-Based-Drug-Design.

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    Shechter, Sharon; Thomas, David R; Lundberg, Lindsay; Pinkham, Chelsea; Lin, Shih-Chao; Wagstaff, Kylie M; Debono, Aaron; Kehn-Hall, Kylene; Jans, David A

    2017-12-18

    Therapeutics are currently unavailable for Venezuelan equine encephalitis virus (VEEV), which elicits flu-like symptoms and encephalitis in humans, with an estimated 14% of cases resulting in neurological disease. Here we identify anti-VEEV agents using in silico structure-based-drug-design (SBDD) for the first time, characterising inhibitors that block recognition of VEEV capsid protein (C) by the host importin (IMP) α/β1 nuclear transport proteins. From an initial screen of 1.5 million compounds, followed by in silico refinement and screening for biological activity in vitro, we identified 21 hit compounds which inhibited IMPα/β1:C binding with IC50s as low as 5 µM. Four compounds were found to inhibit nuclear import of C in transfected cells, with one able to reduce VEEV replication at µM concentration, concomitant with reduced C nuclear accumulation in infected cells. Further, this compound was inactive against a mutant VEEV that lacks high affinity IMPα/β1:C interaction, supporting the mode of its antiviral action to be through inhibiting C nuclear localization. This successful application of SBDD paves the way for lead optimization for VEEV antivirals, and is an exciting prospect to identify inhibitors for the many other viral pathogens of significance that require IMPα/β1 in their infectious cycle.

  13. Development of a novel monoclonal antibody with reactivity to a wide range of Venezuelan equine encephalitis virus strains

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    Phelps Amanda L

    2009-11-01

    Full Text Available Abstract Background There is currently a requirement for antiviral therapies capable of protecting against infection with Venezuelan equine encephalitis virus (VEEV, as a licensed vaccine is not available for general human use. Monoclonal antibodies are increasingly being developed as therapeutics and are potential treatments for VEEV as they have been shown to be protective in the mouse model of disease. However, to be truly effective, the antibody should recognise multiple strains of VEEV and broadly reactive monoclonal antibodies are rarely and only coincidentally isolated using classical hybridoma technology. Results In this work, methods were developed to reliably derive broadly reactive murine antibodies. A phage library was created that expressed single chain variable fragments (scFv isolated from mice immunised with multiple strains of VEEV. A broadly reactive scFv was identified and incorporated into a murine IgG2a framework. This novel antibody retained the broad reactivity exhibited by the scFv but did not possess virus neutralising activity. However, the antibody was still able to protect mice against VEEV disease induced by strain TrD when administered 24 h prior to challenge. Conclusion A monoclonal antibody possessing reactivity to a wide range of VEEV strains may be of benefit as a generic antiviral therapy. However, humanisation of the murine antibody will be required before it can be tested in humans. Crown Copyright © 2009

  14. Chronic herpes simplex virus encephalitis in childhood.

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    Leen, W.G.; Weemaes, C.M.R.; Verbeek, M.M.; Willemsen, M.A.A.P.; Rotteveel, J.J.

    2006-01-01

    Although herpes simplex virus is a major cause of acute encephalitis in childhood, chronic herpes simplex virus encephalitis has only rarely been reported. This report presents a case of chronic herpes simplex virus encephalitis in a 6-year-old female. Diagnosis was based on the detection of herpes

  15. Vector competence of eastern and western forms of Psorophora columbiae (Diptera: Culicidae) mosquitoes for enzootic and epizootic Venezuelan equine encephalitis virus.

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    Moncayo, Abelardo C; Lanzaro, Gregory; Kang, Wenli; Orozco, Arnoldo; Ulloa, Armando; Arredondo-Jiménez, Juan; Weaver, Scott C

    2008-03-01

    Venezuelan equine encephalitis virus (VEEV) continues to circulate enzootically in Mexico with the potential to re-emerge and cause disease in equines and humans in North America. We infected two geographically distinct mosquito populations of eastern Psorophora columbiae form columbiae (Chiapas, Mexico and Texas, United States) and one mosquito population of western Psorophora columbiae form toltecum (California, United States) with epizootic and enzootic IE VEEV and epizootic IAB VEEV. We detected no differences between epizootic and enzootic IE viruses in their ability to infect any of the mosquito populations analyzed, which suggested that neither species selects for epizootic IE viruses. Psorophora columbiae f. columbiae (Texas) were significantly less susceptible to infection by epizootic IE than Ps. columbiae f. columbiae (Mexico). Psorophora columbiae f. toltecum populations were more susceptible than Ps. columbiae f. columbiae populations to epizootic IE and IAB viruses.

  16. 1,5 iodonaphthyl Azide Inactivated V3526 Protects against Aerosol Challenge with Virulent Venezuelan Equine Encephalitis Virus.

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    2016-06-02

    Vero 76 cells were seeded at a density of 4 x 104 cells /well of a 96-well plate (Corning, VWR Cat #29443-050, Bridgeport, NJ) and incubated overnight...et al. Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection. Virology. 2007;367:307-23...diluted serum samples and incubated overnight at 4oC. Following incubation, sample+virus mixtures were transferred to a 96-well plate containing Vero

  17. A humanised murine monoclonal antibody protects mice from Venezuelan equine encephalitis virus, Everglades virus and Mucambo virus when administered up to 48 h after airborne challenge

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    O' Brien, Lyn M., E-mail: lmobrien@dstl.gov.uk; Goodchild, Sarah A.; Phillpotts, Robert J.; Perkins, Stuart D.

    2012-05-10

    Currently there are no licensed antiviral treatments for the Alphaviruses Venezuelan equine encephalitis virus (VEEV), Everglades virus and Mucambo virus. We previously developed a humanised version of the mouse monoclonal antibody 1A3B-7 (Hu1A3B-7) which exhibited a wide range of reactivity in vitro and was able to protect mice from infection with VEEV. Continued work with the humanised antibody has now demonstrated that it has the potential to be a new human therapeutic. Hu1A3B-7 successfully protected mice from infection with multiple Alphaviruses. The effectiveness of the humanisation process was determined by assessing proliferation responses in human T-cells to peptides derived from the murine and humanised versions of the V{sub H} and V{sub L} domains. This analysis showed that the number of human T-cell epitopes within the humanised antibody had been substantially reduced, indicating that Hu1A3B-7 may have reduced immunogenicity in vivo.

  18. Tick-borne encephalitis virus, Kyrgyzstan.

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    Briggs, Benjamin J; Atkinson, Barry; Czechowski, Donna M; Larsen, Peter A; Meeks, Heather N; Carrera, Juan P; Duplechin, Ryan M; Hewson, Roger; Junushov, Asankadyr T; Gavrilova, Olga N; Breininger, Irena; Phillips, Carleton J; Baker, Robert J; Hay, John

    2011-05-01

    Tick-borne encephalitis virus (TBEV) is an emerging pathogen in Europe and Asia. We investigated TBEV in Kyrgyzstan by collecting small mammals and ticks from diverse localities and analyzing them for evidence of TBEV infection. We found TBEV circulating in Kyrgyzstan much farther south and at higher altitudes than previously reported.

  19. Tick-Borne Encephalitis Virus, Kyrgyzstan

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    Atkinson, Barry; Czechowski, Donna M.; Larsen, Peter A.; Meeks, Heather N.; Carrera, Juan P.; Duplechin, Ryan M.; Hewson, Roger; Junushov, Asankadyr T.; Gavrilova, Olga N.; Breininger, Irena; Phillips, Carleton J.; Baker, Robert J.; Hay, John

    2011-01-01

    Tick-borne encephalitis virus (TBEV) is an emerging pathogen in Europe and Asia. We investigated TBEV in Kyrgyzstan by collecting small mammals and ticks from diverse localities and analyzing them for evidence of TBEV infection. We found TBEV circulating in Kyrgyzstan much farther south and at higher altitudes than previously reported. PMID:21529400

  20. Venezuelan equine encephalitis virus replicon particle vaccine protects nonhuman primates from intramuscular and aerosol challenge with ebolavirus.

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    Herbert, Andrew S; Kuehne, Ana I; Barth, James F; Ortiz, Ramon A; Nichols, Donald K; Zak, Samantha E; Stonier, Spencer W; Muhammad, Majidat A; Bakken, Russell R; Prugar, Laura I; Olinger, Gene G; Groebner, Jennifer L; Lee, John S; Pratt, William D; Custer, Max; Kamrud, Kurt I; Smith, Jonathan F; Hart, Mary Kate; Dye, John M

    2013-05-01

    There are no vaccines or therapeutics currently approved for the prevention or treatment of ebolavirus infection. Previously, a replicon vaccine based on Venezuelan equine encephalitis virus (VEEV) demonstrated protective efficacy against Marburg virus in nonhuman primates. Here, we report the protective efficacy of Sudan virus (SUDV)- and Ebola virus (EBOV)-specific VEEV replicon particle (VRP) vaccines in nonhuman primates. VRP vaccines were developed to express the glycoprotein (GP) of either SUDV or EBOV. A single intramuscular vaccination of cynomolgus macaques with VRP expressing SUDV GP provided complete protection against intramuscular challenge with SUDV. Vaccination against SUDV and subsequent survival of SUDV challenge did not fully protect cynomolgus macaques against intramuscular EBOV back-challenge. However, a single simultaneous intramuscular vaccination with VRP expressing SUDV GP combined with VRP expressing EBOV GP did provide complete protection against intramuscular challenge with either SUDV or EBOV in cynomolgus macaques. Finally, intramuscular vaccination with VRP expressing SUDV GP completely protected cynomolgus macaques when challenged with aerosolized SUDV, although complete protection against aerosol challenge required two vaccinations with this vaccine.

  1. Venezuelan equine Encephalitis virus capsid protein forms a tetrameric complex with CRM1 and importin alpha/beta that obstructs nuclear pore complex function.

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    Atasheva, Svetlana; Fish, Alexander; Fornerod, Maarten; Frolova, Elena I

    2010-05-01

    Development of the cellular antiviral response requires nuclear translocation of multiple transcription factors and activation of a wide variety of cellular genes. To counteract the antiviral response, several viruses have developed an efficient means of inhibiting nucleocytoplasmic traffic. In this study, we demonstrate that the pathogenic strain of Venezuelan equine encephalitis virus (VEEV) has developed a unique mechanism of nuclear import inhibition. Its capsid protein forms a tetrameric complex with the nuclear export receptor CRM1 and the nuclear import receptor importin alpha/beta. This unusual complex accumulates in the center channel of the nuclear pores and blocks nuclear import mediated by different karyopherins. The inhibitory function of VEEV capsid protein is determined by a short 39-amino-acid-long peptide that contains both nuclear import and supraphysiological nuclear export signals. Mutations in these signals or in the linker peptide attenuate or completely abolish capsid-specific inhibition of nuclear traffic. The less pathogenic VEEV strains contain a wide variety of mutations in this peptide that affect its inhibitory function in nuclear import. Thus, these mutations appear to be the determinants of this attenuated phenotype. This novel mechanism of inhibiting nuclear transport also shows that the nuclear pore complex is vulnerable to unusual cargo receptor complexes and sheds light on the importance of finely adjusted karyopherin-nucleoporin interactions for efficient cargo translocation.

  2. Epidemiology of Emergent Madariaga Encephalitis in a Region with Endemic Venezuelan Equine Encephalitis: Initial Host Studies and Human Cross-Sectional Study in Darien, Panama.

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    Amy Y Vittor

    2016-04-01

    Full Text Available Neurotropic arboviral infections are an important cause of encephalitis. A zoonotic, vector-borne alphavirus, Madariaga virus (MADV; formerly known as South American eastern equine encephalitis virus, caused its first documented human outbreak in 2010 in Darien, Panama, where the genetically similar Venezuelan equine encephalitis virus (VEEV is endemic. We report the results of a seroprevalence survey of animals and humans, illustrating contrasting features of MADV and VEEV ecology and epidemiology.Small mammals were trapped in 42 sites in Darien, Panama, using Sherman traps, Tomahawk traps, and mist nets for bats. Blood was tested for the presence of neutralizing antibodies to MADV and VEEV. In addition, bird sera collected in 2007 in Chagres, Panama, were tested for MADV and VEEV neutralizing antibodies. Viremia was ascertained by RT-PCR. Human exposure to these two viruses was determined by IgG ELISA, followed by plaque reduction neutralization tests. To identify relevant risk factors for MADV or VEEV exposure, logistic regression analysis was performed, and the most parsimonious model was selected based on the Akaike information criterion.The animal survey yielded 32 bats (16 species, 556 rodents (12 species, and 20 opossums (4 species. The short-tailed cane mouse (Zygodontomys brevicauda found abundantly in pasture and farms, had the highest MADV seroprevalence (8.3%. For VEEV, the shrub and forest-dwelling long-whiskered rice rat (Transandinomys bolivaris had the highest seroprevalence (19.0%. Viremia was detected in one animal (Z. brevicauda. Of the 159 bird sera (50 species tested, none were positive for either virus. In humans (n = 770, neutralizing antibodies to MADV and VEEV were present in 4.8% and 31.5%, respectively. MADV seropositivity was positively associated with cattle ranching, farming, and fishing. Having VEEV antibodies and shrubs near the house diminished risk. Age, forest work, farming and fishing were risk factors for

  3. Japanese encephalitis: the virus and vaccines.

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    Yun, Sang-Im; Lee, Young-Min

    2014-01-01

    Japanese encephalitis (JE) is an infectious disease of the central nervous system caused by Japanese encephalitis virus (JEV), a zoonotic mosquito-borne flavivirus. JEV is prevalent in much of Asia and the Western Pacific, with over 4 billion people living at risk of infection. In the absence of antiviral intervention, vaccination is the only strategy to develop long-term sustainable protection against JEV infection. Over the past half-century, a mouse brain-derived inactivated vaccine has been used internationally for active immunization. To date, however, JEV is still a clinically important, emerging, and re-emerging human pathogen of global significance. In recent years, production of the mouse brain-derived vaccine has been discontinued, but 3 new cell culture-derived vaccines are available in various parts of the world. Here we review current aspects of JEV biology, summarize the 4 types of JEV vaccine, and discuss the potential of an infectious JEV cDNA technology for future vaccine development.

  4. Human Hendra virus infection causes acute and relapsing encephalitis.

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    Wong, K T; Robertson, T; Ong, B B; Chong, J W; Yaiw, K C; Wang, L F; Ansford, A J; Tannenberg, A

    2009-06-01

    To study the pathology of two cases of human Hendra virus infection, one with no clinical encephalitis and one with relapsing encephalitis. Autopsy tissues were investigated by light microscopy, immunohistochemistry and in situ hybridization. In the patient with acute pulmonary syndrome but not clinical acute encephalitis, vasculitis was found in the brain, lung, heart and kidney. Occasionally, viral antigens were demonstrated in vascular walls but multinucleated endothelial syncytia were absent. In the lung, there was severe inflammation, necrosis and viral antigens in type II pneumocytes and macrophages. The rare kidney glomerulus showed inflammation and viral antigens in capillary walls and podocytes. Discrete necrotic/vacuolar plaques in the brain parenchyma were associated with antigens and viral RNA. Brain inflammation was mild although CD68(+) microglia/macrophages were significantly increased. Cytoplasmic viral inclusions and antigens and viral RNA in neurones and ependyma suggested viral replication. In the case of relapsing encephalitis, there was severe widespread meningoencephalitis characterized by neuronal loss, macrophages and other inflammatory cells, reactive blood vessels and perivascular cuffing. Antigens and viral RNA were mainly found in neurones. Vasculitis was absent in all the tissues examined. The case of acute Hendra virus infection demonstrated evidence of systemic infection and acute encephalitis. The case of relapsing Hendra virus encephalitis showed no signs of extraneural infection but in the brain, extensive inflammation and infected neurones were observed. Hendra virus can cause acute and relapsing encephalitis and the findings suggest that the pathology and pathogenesis are similar to Nipah virus infection.

  5. Herpes simplex encephalitis : from virus to therapy.

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    Rozenberg, Flore; Deback, Claire; Agut, Henri

    2011-06-01

    Herpes simplex virus (HSV) is the cause of herpes simplex encephalitis (HSE), a devastating human disease which occurs in 2-4 cases per million/year. HSE results either from a primary infection or virus reactivation, in accordance with the common pattern of HSV infection which is a chronic lifelong process. However its pathophysiology remains largely unknown and its poor prognosis is in contrast with the usually good tolerance of most clinical herpetic manifestations. HSE is due to HSV type 1 (HSV-1) in most cases but HSV type 2 (HSV-2) may be also implicated, especially in infants in the context of neonatal herpes. Polymerase chain reaction detection of HSV DNA in cerebrospinal fluid is the diagnosis of choice for HSE. Acyclovir, a nucleoside analogue which inhibits viral DNA polymerase activity, is the reference treatment of HSE while foscarnet constitutes an alternative therapy and the efficacy of cidofovir is currently uncertain in that context. The emergence of HSV resistance to acyclovir, a phenomenon which is mainly observed among immunocompromised patients, is a current concern although no case of HSE due to an acyclovir-resistant HSV strain has been reported to date. Nevertheless the identification and development of novel therapeutic strategies against HSV appears to be a non dispensable objective for future research in virology.

  6. Epstein-Barr virus encephalitis and encephalomyelitis: MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Shian, W.J. [Department of Pediatrics, Tao-Yuan Veterans Hospital, No. 100, Sec 3, Cheng-Kung Rd, City of Tao-Yuan, Taiwan (Taiwan, Province of China); Chi, C.S. [Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan (Taiwan, Province of China)

    1996-09-01

    The purpose of this project is to investigate the clinical and brain MR characteristics of Epstein-Barr virus (EBV) encephalitis and encephalomyelitis. Clinical and 30 MR findings of 29 patients with EBV encephalitis or encephalomyelitis were retrospectively reviewed. Patients included 24 with encephalitis, 3 with encephalomyelitis, and 2 with brain-stem encephalitis. Altered consciousness, seizures, visual hallucination, and acute psychotic reaction were the common presentations. Eight patients had positive MR findings. These included T2 prolongation over gray and white matter, periventricular leukomalacia, and brain atrophy. Transient T2 prolongation over gray and white matter was found in one patient. Our results indicate that EBV encephalitis and encephalomyelitis have a wide range of both clinical and MR findings. The MR lesions may disappear in a short period, so the timing for the MR scan may be critical. (orig.). With 5 figs., 2 tabs.

  7. Unilateral Negative Myoclonus Caused by Herpes Simplex Virus Encephalitis

    Directory of Open Access Journals (Sweden)

    Jin-Mo Park

    2011-05-01

    Full Text Available Various neurologic manifestations of herpes simplex virus (HSV encephalitis have been reported on the literatures. Chorea, ballism, choreoathetosis and myoclonus were reported as movement disorders which might be related with brain lesion by HSV encephalitis, but negative myoclonus (NM has never been reported before. NM can be characterized as a shock-like involuntary jerky movement caused by a sudden, brief interruption of muscle activity. We experienced a case of HSV encephalitis with NM in unilateral arm and leg. In polygraphic monitoring, electroencephalography (EMG silent periods are 50–250 ms in duration with no detectable EMG correlate.

  8. Affinity (tropism) of caprine arthritis encephalitis virus for brain cells ...

    African Journals Online (AJOL)

    In this study, explant cultures prepared from the brain of new-born goat-kid were infected with. Caprine Arthritis Encephalitis (CAE) virus- a retrovirus affecting goats. The specific brain cell types infected by the (CAE) virus were determined using reverse-transcription polymerase chain reaction (RTPCR) and transmission ...

  9. Identification and isolation of Genotype-I Japanese Encephalitis virus from encephalitis patients

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    Gao Xiaoyan

    2010-11-01

    Full Text Available Abstract Historically, Japanese Encephalitis virus (JEV genotype III (GIII has been responsible for human diseases. In recent years, JEV genotype I (GI has been isolated from mosquitoes collected in numerous countries, but has not been isolated from patients with encephalitis. In this study, we report recovery of JEV GI live virus and identification of JEV GI RNA from cerebrospinal fluid (CSF of encephalitis patients in JE endemic areas of China. Whole-genome sequencing and molecular phylogenetic analysis of the JEV isolate from the CSF samples was performed. The isolate in this study is highly similar to other JEV GI strains which isolated from mosquitoes at both the nucleotide and deduced amino acid levels. Phylogenetic analysis based on the genomic sequence showed that the isolate belongs to JEV GI, which is consistent with the phylogenetic analysis based on the pre-membrane (PrM and Glycoprotein genes. As a conclusion, this is the first time to isolate JEV GI strain from CSF samples of encephalitis patients, so continuous survey and evaluate the infectivity and pathogenecity of JEV GI strains are necessary, especially for the JEV GI strains from encephalitis patients. With respect to the latter, because all current JEV vaccines (live and inactivated are derived from JEV GIII strains, future studies should be aimed at investigating and monitoring cross-protection of the human JEV GI isolates against widely used JEV vaccines.

  10. Herpes Simplex Virus (HSV-1 Encephalitis Mimicking Glioblastoma: Case Report and Review of the Literature

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    Burke A. Cunha

    2014-12-01

    Full Text Available Glioblastoma multiforme (GBM often presents as a brain mass with encephalitis. In a patient with GBM, subsequent presentation with new onset encephalitis may be due to another GBM or Herpes simplex virus 1 (HSV-1 encephalitis. We present a case of HSV-1 encephalitis mimicking GBM in a patient with previous GBM.

  11. Genotype v Japanese encephalitis virus is emerging

    National Research Council Canada - National Science Library

    Li, Ming-Hua; Fu, Shi-Hong; Chen, Wei-Xin; Wang, Huan-Yu; Guo, Yu-Hong; Liu, Qi-Yong; Li, Yi-Xing; Luo, Hui-Ming; Da, Wa; Duo Ji, Dun Zhu; Ye, Xiu-Min; Liang, Guo-Dong

    2011-01-01

    Japanese encephalitis (JE) is a global public health issue that has spread widely to more than 20 countries in Asia and has extended its geographic range to the south Pacific region including Australia...

  12. New potential antivirals against tick-borne encephalitis virus infection

    OpenAIRE

    VESELKOVÁ, Barbora

    2013-01-01

    The experimental work of the thesis was concentrated on studying of the inhibition effect of twenty-six chemical substances on tick-borne encephalitis virus. The substances showing inhibition effect in High Throughput Screening assay were processed to Cytotoxicity assay, where their toxic effect on tissue cell cultures was determined. Subsequently, substances with inhibition effect and no cytotoxic effect were incubated with cell culture and virus in two different incubation time periods and ...

  13. Nipah virus encephalitis: A cause for concern for Indian neurologists?

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    Halder Amit

    2006-01-01

    Full Text Available The first and only recorded outbreak of Nipah virus (NV encephalitis in India occurred in the winter of 2001, although the causative organism could only be identified 5 years down the line in 2006. The first ever-recorded outbreak of NV encephalitis occurred in the Malaysian peninsula in 1998-99; though between 2001 and 2005, at least four outbreaks occurred in our neighboring country of Bangladesh. The threat of further outbreaks of this dangerous disease looms large on the Indian subcontinent, given the natural reservoir of the definitive host, namely, fruit-eating bats of the genus Pteropus. This review would briefly highlight the epidemiology, clinical aspects and diagnosis of NV encephalitis to enlighten the neurological community of the country for early detection and implementation of preventive measures in the event of further outbreaks, especially those which are generally passed of as ′mystery diseases′ in the lay press and even by governmental agencies.

  14. Replicon particles of Venezuelan equine encephalitis virus as a reductionist murine model for encephalitis.

    Science.gov (United States)

    Schäfer, Alexandra; Whitmore, Alan C; Konopka, Jennifer L; Johnston, Robert E

    2009-05-01

    Venezuelan equine encephalitis virus (VEE) replicon particles (VRP) were used to model the initial phase of VEE-induced encephalitis in the mouse brain. VRP can target and infect cells as VEE, but VRP do not propagate beyond the first infected cell due to the absence of the structural genes. Direct intracranial inoculation of VRP into mice induced acute encephalitis with signs similar to the neuronal phase of wild-type VEE infection and other models of virus-induced encephalitis. Using the previously established VRP-mRNP tagging system, a new method to distinguish the host responses in infected cells from those in uninfected bystander cell populations, we detected a robust and rapid innate immune response in the central nervous system (CNS) by infected neurons and uninfected bystander cells. Moreover, this innate immune response in the CNS compromised blood-brain barrier integrity, created an inflammatory response, and directed an adaptive immune response characterized by proliferation and activation of microglia cells and infiltration of inflammatory monocytes, in addition to CD4(+) and CD8(+) T lymphocytes. Taken together, these data suggest that a naïve CNS has an intrinsic potential to induce an innate immune response that could be crucial to the outcome of the infection by determining the composition and dynamics of the adaptive immune response. Furthermore, these results establish a model for neurotropic virus infection to identify host and viral factors that contribute to invasion of the brain, the mechanism(s) whereby the adaptive immune response can clear the infection, and the role of the host innate response in these processes.

  15. Computed tomography in young children with herpes simplex virus encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Sugimoto, T.; Woo, M.; Okazaki, H.; Nishida, N.; Hara, T.; Yasuhara, A.; Kasahara, M.; Kobayashi, Y.

    1985-09-01

    Computed tomographic (CT) scans were obtained from eight infants and young children with herpes simplex virus encephalitis. In two cases the initial scan showed diffuse edematous changes as a mass effect without laterality. Unilateral localized low attenuation in the initial scan was evident 4 days after the onset in one patient, and high attenuation in the initial scan appeared on the 6th day in another patient, but in general, it was not possible to establish an early diagnosis of herpes simplex virus encephalitis from CT scan. In the longitudinal study the calcification with ventriculomegaly appeared in 3 of 5 survivors, and gyriform calcification in 2 of 3 patients, respectively. The appearance of multicystic encephalomalacia was evident in one patient 6 months after the onset of neonatal herpes simplex encephalitis. It is shown that the CT findings of neonates and young children with herpes simplex encephalitis are different from those of older children and adults, and the importance of longitudinal CT studies was stressed in clarifying the pathophysiology of the central nervous system involvement in survivors.

  16. Computed tomography in young children with herpes simplex virus encephalitis.

    Science.gov (United States)

    Sugimoto, T; Woo, M; Okazaki, H; Nishida, N; Hara, T; Yasuhara, A; Kasahara, M; Kobayashi, Y

    1985-01-01

    Computed tomographic (CT) scans were obtained from eight infants and young children with herpes simplex virus encephalitis. In two cases the initial scan showed diffuse edematous changes as a mass effect without laterality. Unilateral localized low attenuation in the initial scan was evident 4 days after the onset in one patient, and high attenuation in the initial scan appeared on the 6th day in another patient, but in general, it was not possible to establish an early diagnosis of herpes simplex virus encephalitis from CT scan. In the longitudinal study the calcification with ventriculomegaly appeared in 3 of 5 survivors, and gyriform calcification in 2 of 3 patients, respectively. The appearance of multicystic encephalomalacia was evident in one patient 6 months after the onset of neonatal herpes simplex encephalitis. It is shown that the CT findings of neonates and young children with herpes simplex encephalitis are different from those of older children and adults, and the importance of longitudinal CT studies was stressed in clarifying the pathophysiology of the central nervous system involvement in survivors.

  17. TLR3 Mutations in Adult Patients With Herpes Simplex Virus and Varicella-Zoster Virus Encephalitis.

    Science.gov (United States)

    Sironi, Manuela; Peri, Anna Maria; Cagliani, Rachele; Forni, Diego; Riva, Stefania; Biasin, Mara; Clerici, Mario; Gori, Andrea

    2017-05-01

    Defects in genes of the Toll-like receptor 3 (TLR3) pathway are associated with susceptibility to herpes simplex virus type 1 encephalitis (HSE). We analyzed a cohort of 11 adult Italian patients in whom viral encephalitis developed. We detected 2 rare missense mutations in TLR3: 1 in a patient with HSE (p.Leu297Val) and 1 in a patient with varicella-zoster virus encephalitis (p.Leu199Phe). Both mutations are extremely rare in human populations and have pathogenicity scores highly suggestive of a functional effect. Data herein expand the phenotypic spectrum of TLR3 mutations to varicella-zoster virus encephalitis and support the role of TLR3 genetic defects as risk factors for HSE in adults. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  18. The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity.

    Directory of Open Access Journals (Sweden)

    Ann R Hunt

    2010-07-01

    Full Text Available Venezuelan equine encephalitis virus (VEEV is responsible for VEE epidemics that occur in South and Central America and the U.S. The VEEV envelope contains two glycoproteins E1 (mediates cell membrane fusion and E2 (binds receptor and elicits virus neutralizing antibodies. Previously we constructed E1 and E2 epitope maps using murine monoclonal antibodies (mMAbs. Six E2 epitopes (E2(c,d,e,f,g,h bound VEEV-neutralizing antibody and mapped to amino acids (aa 182-207. Nothing is known about the human antibody repertoire to VEEV or epitopes that engage human virus-neutralizing antibodies. There is no specific treatment for VEE; however virus-neutralizing mMAbs are potent protective and therapeutic agents for mice challenged with VEEV by either peripheral or aerosol routes. Therefore, fully human MAbs (hMAbs with virus-neutralizing activity should be useful for prevention or clinical treatment of human VEE.We used phage-display to isolate VEEV-specific hFabs from human bone marrow donors. These hFabs were characterized by sequencing, specificity testing, VEEV subtype cross-reactivity using indirect ELISA, and in vitro virus neutralization capacity. One E2-specific neutralizing hFAb, F5n, was converted into IgG, and its binding site was identified using competitive ELISA with mMAbs and by preparing and sequencing antibody neutralization-escape variants.Using 11 VEEV-reactive hFabs we constructed the first human epitope map for the alphaviral surface proteins E1 and E2. We identified an important neutralization-associated epitope unique to the human immune response, E2 aa115-119. Using a 9 A resolution cryo-electron microscopy map of the Sindbis virus E2 protein, we showed the probable surface location of this human VEEV epitope.The VEEV-neutralizing capacity of the hMAb F5 nIgG is similar to that exhibited by the humanized mMAb Hy4 IgG. The Hy4 IgG has been shown to limit VEEV infection in mice both prophylactically and therapeutically. Administration

  19. Degradation of Japanese encephalitis virus by neutrophils

    Science.gov (United States)

    SRIVASTAVA, SONILIKA; KHANNA, NIVEDITA; SAXENA, S K; SINGH, ADITI; MATHUR, ASHA; DHOLE, T N

    1999-01-01

    The ability of neutrophils to degrade the phagocytosed Japanese encephalitis (JE) virion, via triggering of the respiratory burst and generation of toxic radicals has been investigated. JEV or JEV-induced macrophage derived factor (MDF) induces increase in intracellular oxidative signals with generation of superoxide anion (O−2), via activation of cytosolic NADPH and subsequent formation of hydrogen peroxide, with maximum activity on day 7 post infection. The response was sensitive to anti-MDF antibody treatment. Further, the study revealed rapid degradation of phagocytosed JE viral protein and nucleic acid. The viral protein degradation was partially dependent on the generation of toxic oxygen species as it could be abrogated by pretreatment of the cells with staurosporine. PMID:10365083

  20. Epstein-Barr Virus Encephalitis in an Immunocompetent Child: A Case Report and Management of Epstein-Barr Virus Encephalitis

    Directory of Open Access Journals (Sweden)

    Gulsen Akkoc

    2016-01-01

    Full Text Available Epstein-Barr virus (EBV usually causes mild, asymptomatic, and self-limited infections in children and adults; however, it may occasionally lead to severe conditions such as neurological diseases, malignant diseases, hepatic failure, and myocarditis. Epstein-Barr virus-related neurological disorders include meningitis, encephalitis, and cranial or peripheral neuritis, which are mostly seen in immunocompromised patients. The therapeutic modalities for EBV-related severe organ damage including central nervous system manifestations are still uncertain. Herein, we describe a seven-year-old boy with EBV encephalitis who presented with prolonged fever, exudative pharyngitis, reduced consciousness, and neck stiffness. Cranial magnetic resonance imaging showed contrast enhancement in the bilateral insular cortex and the right hypothalamus. The diagnosis was made by EBV-DNA amplification in both the blood and cerebrospinal fluid samples. He was discharged with acyclovir therapy without any sequelae.

  1. Subclinical infection without encephalitis in mice following intranasal exposure to Nipah virus-Malaysia and Nipah virus-Bangladesh

    OpenAIRE

    Dups, Johanna; Middleton, Deborah; Long, Fenella; Arkinstall, Rachel; Glenn A Marsh; Wang, Lin-Fa

    2014-01-01

    Background Nipah virus and Hendra virus are closely related and following natural or experimental exposure induce similar clinical disease. In humans, encephalitis is the most serious outcome of infection and, hitherto, research into the pathogenesis of henipavirus encephalitis has been limited by the lack of a suitable model. Recently we reported a wild-type mouse model of Hendra virus (HeV) encephalitis that should facilitate detailed investigations of its neuropathogenesis, including mecha...

  2. Neuronal apoptosis in herpes simplex virus - 1 encephalitis (HSE).

    Science.gov (United States)

    Athmanathan, S; Vydehi, B V; Sundaram, C; Vemuganti, G K; Murthy, J M

    2001-01-01

    Herpes simplex virus infections are encountered often due to their ubiquitous nature. Common sites involved include skin, mucous membrane, genitalia, eye and the nervous system. HSV infection of the central nervous system can be life threatening. Little is known about the pathogenesis of this cataclysmic disease, at the cellular level. Virus induced apoptosis may play a role in the molecular pathogenesis of encephalitis. This study aims to detect the presence of apoptosis: a) In the brain tissue obtained at autopsy from a patient who succumbed to Herpes simplex virus - 1 encephalitis (HSE) and b) In a human glioblastoma cell line (SNB 19). Wedge tissue samples were obtained from the inferior surface of the frontal lobe and fixed in buffered formalin. Tissue sections were stained with haematoxylin and eosin for histopathological analysis. An indirect immunoperoxidase assay was performed for the detection of HSV -1 antigen in the tissue sections. Apoptosis in the brain tissue was detected employing the TUNEL assay (Terminal deoxynucleotidyl Transferase (TdT) mediated deoxy Uridine Triphosphate Nick End Labeling) using a commerically available kit (TdT Fragel DNA fragmentation detection kit, Oncogene Research Products, CA). HSV-1 induced apoptosis of SNB 19 cells were detected in-vitro by: a) Membrane blebbing assay and b) Hoechst 33258 staining. Classical features of viral encephalitis including the presence of intranuclear inclusions, neuronal loss and perivascular cuffing were seen in the tissue sections. The immunoperoxidase assay revealed the presence of abundant viral antigen in the neurons, microglial and satellite cells. TUNEL assay revealed many apoptotic neurons, microglial and satellite cells. In-vitro assays showed evidence of HSV-1 induced apoptosis in the SNB 19 cell line. These results suggest that virus induced apoptosis may play a role in the molecular pathogenesis of HSE. Further studies are warranted to elucidate the role of HSV-1 induced apoptosis

  3. Vectors expressing chimeric Japanese encephalitis dengue 2 viruses.

    Science.gov (United States)

    Wei, Y; Wang, S; Wang, X

    2014-01-01

    Vectors based on self-replicating RNAs (replicons) of flaviviruses are becoming powerful tool for expression of heterologous genes in mammalian cells and development of novel antiviral and anticancer vaccines. We constructed two vectors expressing chimeric viruses consisting of attenuated SA14-14-2 strain of Japanese encephalitis virus (JEV) in which the PrM/M-E genes were replaced fully or partially with those of dengue 2 virus (DENV-2). These vectors, named pJED2 and pJED2-1770 were transfected to BHK-21 cells and produced chimeric viruses JED2V and JED2-1770V, respectively. The chimeric viruses could be passaged in C6/36 but not BHK-21 cells. The chimeric viruses produced in C6/36 cells CPE 4-5 days after infection and RT-PCR, sequencing, immunofluorescence assay (IFA) and Western blot analysis confirmed the chimeric nature of produced viruses. The immunogenicity of chimeric viruses in mice was proved by detecting DENV-2 E protein-specific serum IgG antibodies with neutralization titer of 10. Successful preparation of infectious clones of chimeric JEV-DENV-2 viruses showed that JEV-based expression vectors are fully functional.

  4. Neutralising antibodies for Mayaro virus in Pantanal, Brazil

    Directory of Open Access Journals (Sweden)

    Alex Pauvolid-Corrêa

    2015-02-01

    Full Text Available The Pantanal hosts diverse wildlife species and therefore is a hotspot for arbovirus studies in South America. A serosurvey for Mayaro virus (MAYV, eastern (EEEV, western (WEEV and Venezuelan (VEEV equine encephalitis viruses was conducted with 237 sheep, 87 free-ranging caimans and 748 equids, including 37 collected from a ranch where a neurologic disorder outbreak had been recently reported. Sera were tested for specific viral antibodies using plaque-reduction neutralisation test. From a total of 748 equids, of which 264 were immunised with vaccine composed of EEEV and WEEV and 484 had no history of immunisation, 10 (1.3% were seropositive for MAYV and two (0.3% for VEEV using criteria of a ≥ 4-fold antibody titre difference. Among the 484 equids without history of immunisation, 48 (9.9% were seropositive for EEEV and four (0.8% for WEEV using the same criteria. Among the sheep, five were sero- positive for equine encephalitis alphaviruses, with one (0.4% for EEEV, one (0.4% for WEEV and three (1.3% for VEEV. Regarding free-ranging caimans, one (1.1% and three (3.4%, respectively, had low titres for neutralising antibodies to VEEV and undetermined alphaviruses. The neurological disorder outbreak could not be linked to the alphaviruses tested. Our findings represent strong evidence that MAYV and all equine encephalitis alphaviruses circulated in the Pantanal.

  5. Neutralising antibodies for Mayaro virus in Pantanal, Brazil.

    Science.gov (United States)

    Pauvolid-Corrêa, Alex; Juliano, Raquel Soares; Campos, Zilca; Velez, Jason; Nogueira, Rita Maria Ribeiro; Komar, Nicholas

    2015-02-01

    The Pantanal hosts diverse wildlife species and therefore is a hotspot for arbovirus studies in South America. A serosurvey for Mayaro virus (MAYV), eastern (EEEV), western (WEEV) and Venezuelan (VEEV) equine encephalitis viruses was conducted with 237 sheep, 87 free-ranging caimans and 748 equids, including 37 collected from a ranch where a neurologic disorder outbreak had been recently reported. Sera were tested for specific viral antibodies using plaque-reduction neutralisation test. From a total of 748 equids, of which 264 were immunised with vaccine composed of EEEV and WEEV and 484 had no history of immunisation, 10 (1.3%) were seropositive for MAYV and two (0.3%) for VEEV using criteria of a ≥ 4-fold antibody titre difference. Among the 484 equids without history of immunisation, 48 (9.9%) were seropositive for EEEV and four (0.8%) for WEEV using the same criteria. Among the sheep, five were sero- positive for equine encephalitis alphaviruses, with one (0.4%) for EEEV, one (0.4%) for WEEV and three (1.3%) for VEEV. Regarding free-ranging caimans, one (1.1%) and three (3.4%), respectively, had low titres for neutralising antibodies to VEEV and undetermined alphaviruses. The neurological disorder outbreak could not be linked to the alphaviruses tested. Our findings represent strong evidence that MAYV and all equine encephalitis alphaviruses circulated in the Pantanal.

  6. A new model for Hendra virus encephalitis in the mouse.

    Directory of Open Access Journals (Sweden)

    Johanna Dups

    Full Text Available Hendra virus (HeV infection in humans is characterized by an influenza like illness, which may progress to pneumonia or encephalitis and lead to death. The pathogenesis of HeV infection is poorly understood, and the lack of a mouse model has limited the opportunities for pathogenetic research. In this project we reassessed the role of mice as an animal model for HeV infection and found that mice are susceptible to HeV infection after intranasal exposure, with aged mice reliably developing encephalitic disease. We propose an anterograde route of neuroinvasion to the brain, possibly along olfactory nerves. This is supported by evidence for the development of encephalitis in the absence of viremia and the sequential distribution of viral antigen along pathways of olfaction in the brain of intranasally challenged animals. In our studies mice developed transient lower respiratory tract infection without progressing to viremia and systemic vasculitis that is common to other animal models. These studies report a new animal model of HeV encephalitis that will allow more detailed studies of the neuropathogenesis of HeV infection, particularly the mode of viral spread and possible sequestration within the central nervous system; investigation of mechanisms that moderate the development of viremia and systemic disease; and inform the development of improved treatment options for human patients.

  7. St. Louis encephalitis virus possibly transmitted through blood transfusion-Arizona, 2015.

    Science.gov (United States)

    Venkat, Heather; Adams, Laura; Sunenshine, Rebecca; Krow-Lucal, Elisabeth; Levy, Craig; Kafenbaum, Tammy; Sylvester, Tammy; Smith, Kirk; Townsend, John; Dosmann, Melissa; Kamel, Hany; Patron, Roberto; Kuehnert, Matthew; Annambhotla, Pallavi; Basavaraju, Sridhar V; Rabe, Ingrid B

    2017-12-01

    St. Louis encephalitis virus is a mosquito-borne flavivirus that infrequently causes epidemic central nervous system infections. In the United States, blood donors are not screened for St. Louis encephalitis virus infection, and transmission through blood transfusion has not been reported. During September 2015, St. Louis encephalitis virus infection was confirmed in an Arizona kidney transplant recipient. An investigation was initiated to determine the infection source. The patient was interviewed, and medical records were reviewed. To determine the likelihood of mosquito-borne infection, mosquito surveillance data collected at patient and blood donor residences in timeframes consistent with their possible exposure periods were reviewed. To investigate other routes of exposure, organ and blood donor and recipient specimens were obtained and tested for evidence of St. Louis encephalitis virus infection. The patient presented with symptoms of central nervous system infection. Recent St. Louis encephalitis virus infection was serologically confirmed. The organ donor and three other organ recipients showed no laboratory or clinical evidence of St. Louis encephalitis virus infection. Among four donors of blood products received by the patient via transfusion, one donor had a serologically confirmed, recent St. Louis encephalitis virus infection. Exposure to an infected mosquito was unlikely based on the patient's minimal outdoor exposure. In addition, no St. Louis encephalitis virus-infected mosquito pools were identified around the patient's residence. This investigation provides evidence of the first reported possible case of St. Louis encephalitis virus transmission through blood product transfusion. Health care providers and public health professionals should maintain heightened awareness for St. Louis encephalitis virus transmission through blood transfusion in settings where outbreaks are identified. © 2017 AABB.

  8. Phylogeography of Japanese encephalitis virus: genotype is associated with climate.

    Directory of Open Access Journals (Sweden)

    Amy J Schuh

    Full Text Available The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate.

  9. Nipah virus: an emergent paramyxovirus causing severe encephalitis in humans.

    Science.gov (United States)

    Bellini, William J; Harcourt, Brian H; Bowden, Nadine; Rota, Paul A

    2005-10-01

    Nipah virus is a recently emergent paramyxovirus that is capable of causing severe disease in both humans and animals. The first outbreak of Nipah virus occurred in Malaysia and Singapore in 1999 and, more recently, outbreaks were detected in Bangladesh. In humans, Nipah virus causes febrile encephalitis with respiratory syndrome that has a high mortality rate. The reservoir for Nipah virus is believed to be fruit bats, and humans are infected by contact with infected bats or by contact with an intermediate animal host such as pigs. Person to person spread of the virus has also been described. Nipah virus retains many of the genetic and biologic properties found in other paramyxoviruses, though it also has several unique characteristics. However, the virologic characteristics that allow the virus to cause severe disease over a broad host range, and the epidemiologic, environmental and virologic features that favor transmission to humans are unknown. This review summarizes what is known about the virology, epidemiology, pathology, diagnosis and control of this novel pathogen.

  10. Sensitivity of Toxorhynchites amboinensis mosquitoes versus chicken embryonic cell cultures for assays of Venezuelan encephalitis virus.

    Science.gov (United States)

    Scherer, W F; Chin, J

    1981-05-01

    Toxorhynchites amboinensis mosquitoes inoculated intrathoracically with Venezuelan encephalitis virus and tested for infectious virus 12 to 19 days later by inoculation of primary chicken embryonic cell cultures yielded approximately the same titers of virus as did direct inoculation of cultures, with counting of plaques 3 days thereafter. Titers were slightly higher in T. amboinensis for three virus strains, equal for two virus strains, and slightly lower for two virus strains. Comparative titers of four strains were similar, whether virus suspensions came from infectious vertebrate cells or infected invertebrate (T. amboinensis) cells. Each of the seven strains of Venezuelan encephalitis virus reached virus concentrations of 10(4.2) to 10(5.1) plaque-forming units in individual T. amboinensis mosquitoes after extrinsic incubation periods of 12 to 19 days. No temperature-sensitive (29 versus 37 degrees C) virus was detected in T. amboinensis mosquitoes infected by six strains of Venezuelan encephalitis virus.

  11. Isolation of Saint Louis Encephalitis Virus from a Horse with Neurological Disease in Brazil

    Science.gov (United States)

    Rosa, Roberta; Costa, Erica Azevedo; Marques, Rafael Elias; Oliveira, Taismara Simas; Furtini, Ronaldo; Bomfim, Maria Rosa Quaresma; Teixeira, Mauro Martins; Paixão, Tatiane Alves; Santos, Renato Lima

    2013-01-01

    St. Louis encephalitis virus (SLEV) is a causative agent of encephalitis in humans in the Western hemisphere. SLEV is a positive-sense RNA virus that belongs to the Flavivirus genus, which includes West Nile encephalitis virus, Japanese encephalitis virus, Dengue virus and other medically important viruses. Recently, we isolated a SLEV strain from the brain of a horse with neurological signs in the countryside of Minas Gerais, Brazil. The SLEV isolation was confirmed by reverse-transcription RT-PCR and sequencing of the E protein gene. Virus identity was also confirmed by indirect immunofluorescence using commercial antibodies against SLEV. To characterize this newly isolated strain in vivo, serial passages in newborn mice were performed and led to hemorrhagic manifestations associated with recruitment of inflammatory cells into the central nervous system of newborns. In summary this is the first isolation of SLEV from a horse with neurological signs in Brazil. PMID:24278489

  12. St. Louis Encephalitis

    Science.gov (United States)

    ... Information Virus Transmission Epidemiology & Geographic Distribution Symptoms and Treatment Diagnosis Links & References Fact Sheet Other diseases transmitted by mosquitoes Chikungunya virus Dengue Eastern Equine Encephalitis Japanese Encephalitis La Crosse Encephalitis ...

  13. Sequential MRI, SPECT and PET in respiratory syncytial virus encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Hirayama, K.; Sakazaki, Hiromi; Murakami, Seiko; Yonezawa, Sumiko [Department of Paediatrics, Izumi Municipal Hospital, Osaka (Japan); Fujimoto, Keiji [Dept. of Radiology, Izumi Municipal Hospital, Osaka (Japan); Seto, Toshiyuki; Tanaka, Katsuji; Hattori, Hideji; Matsuoka, Osamu [Dept. of Paediatrics, Osaka City University Medical School, Osaka (Japan); Murata, Ryosuke [Children`s Medical Centre, Osaka City General Hospital, Osaka (Japan)

    1999-04-01

    We report on a 3-year-old girl with respiratory syncytial virus (RSV) encephalitis manifested by disturbance of consciousness, conjugate eye deviation, anuria, truncal ataxia and intention tremor. T2-weighted magnetic resonance imaging (MRI) showed hyperintense areas in the cerebellar cortex. No lesion was detected in the cerebral cortex, pons or spinal cord. The hyperintense areas in the cerebellar cortex diminished with recovery from the clinical manifestations and had resolved 2 months after onset. The MRI lesions in the cerebellum were considered to be due to oedema. SPECT and positron emission tomography (PET), performed 3 months after onset, disclosed areas of hypoperfusion and hypometabolism at the same sites. One year after onset, MRI showed mild atrophy of the cerebellum. Hypoperfusion on SPECT and hypometabolism on PET remained. Neuroimaging showed that ataxia and tremor in this case were the result of cerebellitis. The patient has no neurological deficit except for mild truncal ataxia. This patient is a rare example of RSV encephalitis. (orig.) With 4 figs., 16 refs.

  14. Crystal Structure of the Japanese Encephalitis Virus Envelope Protein

    Energy Technology Data Exchange (ETDEWEB)

    Luca, Vincent C.; AbiMansour, Jad; Nelson, Christopher A.; Fremont, Daved H. (WU-MED)

    2012-03-13

    Japanese encephalitis virus (JEV) is the leading global cause of viral encephalitis. The JEV envelope protein (E) facilitates cellular attachment and membrane fusion and is the primary target of neutralizing antibodies. We have determined the 2.1-{angstrom} resolution crystal structure of the JEV E ectodomain refolded from bacterial inclusion bodies. The E protein possesses the three domains characteristic of flavivirus envelopes and epitope mapping of neutralizing antibodies onto the structure reveals determinants that correspond to the domain I lateral ridge, fusion loop, domain III lateral ridge, and domain I-II hinge. While monomeric in solution, JEV E assembles as an antiparallel dimer in the crystal lattice organized in a highly similar fashion as seen in cryo-electron microscopy models of mature flavivirus virions. The dimer interface, however, is remarkably small and lacks many of the domain II contacts observed in other flavivirus E homodimers. In addition, uniquely conserved histidines within the JEV serocomplex suggest that pH-mediated structural transitions may be aided by lateral interactions outside the dimer interface in the icosahedral virion. Our results suggest that variation in dimer structure and stability may significantly influence the assembly, receptor interaction, and uncoating of virions.

  15. Purpura fulminans associated with acute West Nile virus encephalitis.

    Science.gov (United States)

    Shah, Sheevam; Fite, Laura Paul; Lane, Natalie; Parekh, Palak

    2016-02-01

    Purpura fulminans is a progressive thrombotic disorder that presents with widespread purpura due to deficiency or dysfunction of protein C or protein S. Lesions present as well-demarcated erythematous macules that progress to irregular areas of hemorrhagic necrosis.West Nile virus is a member of the Flaviviridae family transmitted to humans through the bite of various mosquito species. It manifests as West Nile fever in 25% of those infected and less commonly as neuroinvasive disease. An African American man in his fortiespresented with altered mental status and was noted to have evidence of disseminated intravascular coagulation according to his lab data. He then developed dusky skin discoloration and systemic flaccid bullae with desquamation. Biopsy was consistent with purpura fulminans and the patient eventually developed symmetric peripheral gangrene, requiring amputations of all four extremities. Infectious work up revealed positive testing for IgM and IgG antibodies in serum and cerebrospinal fluid leading to the diagnosis of acute West Nile Virus encephalitis. We present this case to describe the rarely reported association of purpura fulminans with West Nile Virus infection. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Japanese encephalitis virus infection, diagnosis and control in domestic animals.

    Science.gov (United States)

    Mansfield, Karen L; Hernández-Triana, Luis M; Banyard, Ashley C; Fooks, Anthony R; Johnson, Nicholas

    2017-03-01

    Japanese encephalitis virus (JEV) is a significant cause of neurological disease in humans throughout Asia causing an estimated 70,000 human cases each year with approximately 10,000 fatalities. The virus contains a positive sense RNA genome within a host-derived membrane and is classified within the family Flaviviridae. Like many flaviviruses, it is transmitted by mosquitoes, particularly those of the genus Culex in a natural cycle involving birds and some livestock species. Spill-over into domestic animals results in a spectrum of disease ranging from asymptomatic infection in some species to acute neurological signs in others. The impact of JEV infection is particularly apparent in pigs. Although infection in adult swine does not result in symptomatic disease, it is considered a significant reproductive problem causing abortion, still-birth and birth defects. Infected piglets can display fatal neurological disease. Equines are also infected, resulting in non-specific signs including pyrexia, but occasionally leading to overt neurological disease that in extreme cases can lead to death. Veterinary vaccination is available for both pigs and horses. This review of JEV disease in livestock considers the current diagnostic techniques available for detection of the virus. Options for disease control and prevention within the veterinary sector are discussed. Such measures are critical in breaking the link to zoonotic transmission into the human population where humans are dead-end hosts. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  17. Rabies direct fluorescent antibody test does not inactivate rabies or eastern equine encephalitis viruses.

    Science.gov (United States)

    Jarvis, Jodie A; Franke, Mary A; Davis, April D

    2016-08-01

    An examination using the routine rabies direct fluorescent antibody test was performed on rabies or Eastern equine encephalitis positive mammalian brain tissue to assess inactivation of the virus. Neither virus was inactivated with acetone fixation nor the routine test, thus laboratory employees should treat all samples as rabies and when appropriate Eastern equine encephalitis positive throughout the whole procedure. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. West Nile virus encephalitis induced opsoclonus-myoclonus syndrome

    Directory of Open Access Journals (Sweden)

    Chad J. Cooper

    2014-04-01

    Full Text Available West Nile virus (WNV is an arthropod borne neurotropic single stranded RNA flavivirus with <1% developing presenting with neurological disease. Immunocompromised and elderly patients are more prone to developing WNV meningitis or encephalitis. Definitive diagnosis of WNV meningoencephalitis is a combination of clinical suspicion and cerebrospinal fluid (CSF serology. Forty-eight year old Caucasian female presented with a sudden onset of altered mental status after being found unresponsive. She was confused with intermittent bouts of alertness/lethargy and unintelligible responses to questioning. Her medical problems included endometrial cancer that was in remission after undergoing a total abdominal hysterectomy with bilateral salpingectomy and postoperative chemotherapy with paclitaxel and carboplatin. Pertinent physical examination revealed muscle strength that was significantly decreased, nuchal rigidity and +2 pitting edema of both lower extremities. Computed tomography and magnetic resonance imaging of the brain were negative for any intracranial pathology. CSF analysis was consistent with aseptic meningitis with all CSF serology being negative except for positive WNV antibody. A few days after being admitted she developed involuntary random movements of her eyes and generalized jerking movements (myoclonus. This was determined to be opsoclonus myoclonus syndrome (OMS induced by the WNV meningoencephalitis. She then received five consecutive days of plasmapheresis with a significant improvement in her neurological status. Opsoclonusmyoclonus syndrome (OMS is a rare neurological disorder associated with chaotic multidirectional eye movements, myoclonus and less frequently cerebellar ataxia. OMS affects as few as 1 in 10,000,000 people per year. The pathogenesis is not fully understood with the majority of cases of opsoclonus-myoclonus syndrome being idiopathic. According to current medical literature there have only been two previous case

  19. Interactions of human microglia cells with Japanese encephalitis virus.

    Science.gov (United States)

    Lannes, Nils; Neuhaus, Viviane; Scolari, Brigitte; Kharoubi-Hess, Solange; Walch, Michael; Summerfield, Artur; Filgueira, Luis

    2017-01-14

    Japanese encephalitis virus (JEV) is a neurotropic flavivirus causing mortality and morbidity in humans. Severe Japanese encephalitis cases display strong inflammatory responses in the central nervous system and an accumulation of viral particles in specific brain regions. Microglia cells are the unique brain-resident immune cell population with potent migratory functions and have been proposed to act as a viral reservoir for JEV. Animal models suggest that the targeting of microglia by JEV is partially responsible for inflammatory reactions in the brain. Nevertheless, the interactions between human microglia and JEV are poorly documented. Using human primary microglia and a new model of human blood monocyte-derived microglia, the present study explores the interaction between human microglia and JEV as well as the role of these cells in viral transmission to susceptible cells. To achieve this work, vaccine-containing inactivated JEV and two live JEV strains were applied on human microglia. Live JEV was non-cytopathogenic to human microglia but increased levels of CCL2, CXCL9 and CXCL10 in such cultures. Furthermore, human microglia up-regulated the expression of the fraktalkine receptor CX3CR1 upon exposure to both JEV vaccine and live JEV. Although JEV vaccine enhanced MHC class II on all microglia, live JEV enhanced MHC class II mainly on CX3CR1+ microglia cells. Importantly, human microglia supported JEV replication, but infectivity was only transmitted to neighbouring cells in a contact-dependent manner. Our findings suggest that human microglia may be a source of neuronal infection and sustain JEV brain pathogenesis.

  20. Immunogenicity of the Inactivated Japanese Encephalitis Virus Vaccine IXIARO in Children From a Japanese Encephalitis Virus-endemic Region.

    Science.gov (United States)

    Dubischar, Katrin L; Kadlecek, Vera; Sablan, Jr Benjamin; Borja-Tabora, Charissa Fay; Gatchalian, Salvacion; Eder-Lingelbach, Susanne; Kiermayr, Sigrid; Spruth, Martin; Westritschnig, Kerstin

    2017-09-01

    Japanese encephalitis (JE) is a major public health concern in Asia and poses a small but potentially fatal threat to travelers from nonendemic countries, including children. No JE vaccine for pediatric use has been available in Europe and the United States. Age-stratified cohorts of children between 2 months and 17 years received 2 doses of Vero cell-derived inactivated JE virus vaccine (IXIARO; Valneva Austria GmbH, Vienna, Austria) administered 28 days apart [half adult dose); ≥3 years, 0.5 mL (full adult dose)]. Immunogenicity endpoints were seroconversion rate, 4-fold increase in JE neutralizing antibody titer and geometric mean titer assessed 56 days and 7 months after the first vaccination in 496 subjects of the intent-to-treat population. The immune response to JE virus at both time points was also analyzed according to prevaccination JE virus and dengue virus serostatus. At day 56, seroconversion was attained in ≥99.2% of subjects with age-appropriate dosing, 4-fold increases in titer were reported for 77.4%-100% in various age groups, and geometric mean titers ranged from 176 to 687, with younger children having the strongest immune response. At month 7, seroconversion was maintained in 85.5%-100% of subjects. Pre-existing JE virus immunity did not impact on immune response at day 56; however, it led to a better persistence of protective antibody titers at month 7. IXIARO is highly immunogenic at both doses tested in the pediatric population, leading to protective antibody titers at day 56 in >99% of subjects who received the age-appropriate dose.

  1. Encephalitis

    Science.gov (United States)

    ... occur through: Breathing in droplets from the nose, mouth, or throat from an infected person Contaminated food or drink Mosquito, tick, and other insect bites Skin contact Different viruses occur in different ...

  2. Japanese encephalitis virus vaccine candidates generated by chimerization with dengue virus type 4.

    Science.gov (United States)

    Gromowski, Gregory D; Firestone, Cai-Yen; Hanson, Christopher T; Whitehead, Stephen S

    2014-05-23

    Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis worldwide and vaccination is one of the most effective ways to prevent disease. A suitable live-attenuated JEV vaccine could be formulated with a live-attenuated tetravalent dengue vaccine for the control of these viruses in endemic areas. Toward this goal, we generated chimeric virus vaccine candidates by replacing the precursor membrane (prM) and envelope (E) protein structural genes of recombinant dengue virus type 4 (rDEN4) or attenuated vaccine candidate rDEN4Δ30 with those of wild-type JEV strain India/78. Mutations were engineered in E, NS3 and NS4B protein genes to improve replication in Vero cells. The chimeric viruses were attenuated in mice and some elicited modest but protective levels of immunity after a single dose. One particular chimeric virus, bearing E protein mutation Q264H, replicated to higher titer in tissue culture and was significantly more immunogenic in mice. The results are compared with live-attenuated JEV vaccine strain SA14-14-2. Published by Elsevier Ltd.

  3. A protective chimeric antibody to tick-borne encephalitis virus.

    Science.gov (United States)

    Baykov, Ivan K; Matveev, Andrey L; Stronin, Oleg V; Ryzhikov, Alexander B; Matveev, Leonid E; Kasakin, Marat F; Richter, Vladimir A; Tikunova, Nina V

    2014-06-17

    The efficiency of several mouse monoclonal antibodies (mAbs) specific to the tick-borne encephalitis virus (TBEV) glycoprotein E in post-exposure prophylaxis was assessed, and mAb14D5 was shown to be the most active of all those studied. It was proven that the hybridoma cell line 14D5 produced one immunoglobulin H chain and two L chains. They were used to construct chimeric antibodies ch14D5a and ch14D5b, the affinity constants of which were 2.6 × 10(10)M(-1) and 1.0 × 10(7)M(-1), respectively, according to the SPR-based ProteOn biosensor assay. The neutralization index (IC50) of ch14D5a was 0.04 μg/ml in the focus reduction neutralization test. In in vivo experiments, ch14D5a at a dose of 10 μg/mouse resulted in a 100% survival of the mice infected with 240 LD50 of TBEV. This chimeric antibody is promising for further development of prevention and therapeutic drugs against TBEV. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. DC-SIGN Increases Japanese Encephalitis Virus Infection

    Directory of Open Access Journals (Sweden)

    Yang Yang, Ali Zohaib, Gong Chen, Jing Ye and Shengbo Cao*

    2013-11-01

    Full Text Available Japanese Encephalitis virus (JEV is a mosquito borne flavivirus that infects macrophages, monocytes and dendritic cells (DCs during in vivo replication. The C-type lectins DC-SIGN and DC-SIGNR have been reported to act as cell attachment factors for diverse array of pathogens. In this study, the effect of these lectins on JEV infection was investigated after the generation of 293T-SIGN (R cell lines expressing DC-SIGN and DC-SIGNR receptors. It was observed that only DC-SIGN but not the DC-SIGNR can act as a viral attachment factor in case of JEV infection. The infection to cells expressing DC-SIGN was efficiently blocked by anti-DC-SIGN and mannan molecules. It was also found that insect derived JEV has higher affinity for DC-SIGN as compare to the mammalian derived JEV. These results initially suggest that DC-SIGN could act as viral attachment receptors (VAR for JEV and enhance JEV infection.

  5. Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas.

    Directory of Open Access Journals (Sweden)

    Naomi L Forrester

    2017-08-01

    Full Text Available Venezuelan equine encephalitis (VEE complex alphaviruses are important re-emerging arboviruses that cause life-threatening disease in equids during epizootics as well as spillover human infections. We conducted a comprehensive analysis of VEE complex alphaviruses by sequencing the genomes of 94 strains and performing phylogenetic analyses of 130 isolates using complete open reading frames for the nonstructural and structural polyproteins. Our analyses confirmed purifying selection as a major mechanism influencing the evolution of these viruses as well as a confounding factor in molecular clock dating of ancestors. Times to most recent common ancestors (tMRCAs could be robustly estimated only for the more recently diverged subtypes; the tMRCA of the ID/IAB/IC/II and IE clades of VEE virus (VEEV were estimated at ca. 149-973 years ago. Evolution of the IE subtype has been characterized by a significant evolutionary shift from the rest of the VEEV complex, with an increase in structural protein substitutions that are unique to this group, possibly reflecting adaptation to its unique enzootic mosquito vector Culex (Melanoconion taeniopus. Our inferred tree topologies suggest that VEEV is maintained primarily in situ, with only occasional spread to neighboring countries, probably reflecting the limited mobility of rodent hosts and mosquito vectors.

  6. Quantification of vector and host competence and abundance for Japanese Encephalitis Virus: a systematic review of the literature.

    Science.gov (United States)

    Japanese encephalitis (JE) is a vector-borne disease caused by the Japanese encephalitis virus (JEV) that affects humans in Eastern and Southeastern Asia. Although it could be prevented by a vaccine, JE has no treatment and the inadvertent introduction of the virus into JEV-free countries, such as t...

  7. A systematic review of the literature to identify and quantify host and vector competence and abundance of Japanese Encephalitis Virus

    Science.gov (United States)

    Japanese Encephalitis virus (JEV) is a mosquito-borne arbovirus that causes endemic and epidemic encephalitis in Eastern and Southeastern Asia. Swine and wading birds serve as reservoirs for the virus, which can be transmitted to humans via mosquitos. Currently, there is no specific treatment availa...

  8. mRNA Capping by Venezuelan Equine Encephalitis Virus nsP1: Functional Characterization and Implications for Antiviral Research.

    Science.gov (United States)

    Li, Changqing; Guillén, Jaime; Rabah, Nadia; Blanjoie, Alexandre; Debart, Françoise; Vasseur, Jean-Jacques; Canard, Bruno; Decroly, Etienne; Coutard, Bruno

    2015-08-01

    Alphaviruses are known to possess a unique viral mRNA capping mechanism involving the viral nonstructural protein nsP1. This enzyme harbors methyltransferase (MTase) and nsP1 guanylylation (GT) activities catalyzing the transfer of the methyl group from S-adenosylmethionine (AdoMet) to the N7 position of a GTP molecule followed by the formation of an m(7)GMP-nsP1 adduct. Subsequent transfer of m(7)GMP onto the 5' end of the viral mRNA has not been demonstrated in vitro yet. Here we report the biochemical characterization of Venezuelan equine encephalitis virus (VEEV) nsP1. We have developed enzymatic assays uncoupling the different reactions steps catalyzed by nsP1. The MTase and GT reaction activities were followed using a nonhydrolyzable GTP (GIDP) substrate and an original Western blot assay using anti-m3G/m(7)G-cap monoclonal antibody, respectively. The GT reaction is stimulated by S-adenosyl-l-homocysteine (Ado-Hcy), the product of the preceding MTase reaction, and metallic ions. The covalent linking between nsP1 and m(7)GMP involves a phosphamide bond between the nucleotide and a histidine residue. Final guanylyltransfer onto RNA was observed for the first time with an alphavirus nsP1 using a 5'-diphosphate RNA oligonucleotide whose sequence corresponds to the 5' end of the viral genome. Alanine scanning mutagenesis of residues H37, H45, D63, E118, Y285, D354, R365, N369, and N375 revealed their respective roles in MT and GT reactions. Finally, the inhibitory effects of sinefungin, aurintricarboxylic acid (ATA), and ribavirin triphosphate on MTase and capping reactions were investigated, providing possible avenues for antiviral research. Emergence or reemergence of alphaviruses represents a serious health concern, and the elucidation of their replication mechanisms is a prerequisite for the development of specific inhibitors targeting viral enzymes. In particular, alphaviruses are able, through an original reaction sequence, to add to their mRNA a cap

  9. Mutation of Asn-475 in the Venezuelan Equine Encephalitis Virus nsP2 Cysteine Protease Leads to a Self-Inhibited State.

    Science.gov (United States)

    Compton, Jaimee R; Mickey, Matthew J; Hu, Xin; Marugan, Juan J; Legler, Patricia M

    2017-11-28

    The alphaviral nsP2 cysteine protease of the Venezuelan equine encephalitis virus (VEEV) is a validated antiviral drug target. Clan CN proteases contain a cysteine protease domain that is intimately packed with an S-adenosyl-l-methionine-dependent RNA methyltransferase (SAM MTase) domain. Within a cleft formed at the interface of these two domains, the peptide substrate is thought to bind. The nucleophilic cysteine can be found within a conserved motif, 475NVCWAK480, which differs from that of papain (22CGSCWAFS29). Mutation of the motif residue, N475, to alanine unexpectedly produced a self-inhibited state in which the N-terminal residues flipped into the substrate-binding cleft. Notably, the N-terminal segment was not hydrolyzed-consistent with a catalytically incompetent state. The N475A mutation resulted in a 70-fold decrease in kcat/Km. A side chain-substrate interaction was predicted by the structure; the S701A mutation led to a 17-fold increase in Km. An Asn at the n-2 position relative to the Cys was also found in the coronaviral papain-like proteases/deubiquitinases (PLpro) of the SARS and MERS viruses, and in several papain-like human ubiquitin specific proteases (USP). The large conformational change in the N475A variant suggests that Asn-475 plays an important role in stabilizing the N-terminal residues and in orienting the carbonyl during nucleophilic attack but does not directly hydrogen bond the oxyanion. The state trapped in crystallo is an unusual result of site-directed mutagenesis but reveals the role of this highly conserved Asn and identifies key substrate-binding contacts that may be exploited by peptide-like inhibitors.

  10. [Susceptibility of Aedes albopictus and Culex pipiens quinquefasciatus to infection with bat Japanese encephalitis virus isolates].

    Science.gov (United States)

    Liu, Shan; Zhang, Qionghua; Zhou, Junhua; Yu, Shouyi; Zheng, Xueli; Chen, Qing

    2012-04-01

    To evaluate the susceptibility of Aedes albopictus and Culex pipiens quinquefasciatus to oral infection with bat Japanese encephalitis virus isolates (GD1 and HN2 strains). Aedes albopictus and Culex pipiens quinquefasciatus were infected orally by GD1 and HN2 strains of bat Japanese encephalitis virus. TaqMan real-time PCR was used to detect the virus and monitor the changes in the viral loads in Aedes albopictus and Culex pipiens quinquefasciatus at a 2-day interval, starting from 4 days till 20 days after the infection. The infected Aedes albopictus and Culex pipiens quinquefasciatus were found positive for the Japanese encephalitis virus from day 4 to day 20. Both Aedes albopictus and Culex pipiens quinquefasciatus were susceptible to infection by GD1 and HN2 strains, but the latter showed a greater susceptibility. The HN2 strain virus appeared to have a greater virulence than the GD1 strain. Aedes albopictus and Culex pipiens quinquefasciatus can carry GD1 and HN2 strains of bat Japanese encephalitis virus isolates.

  11. Veevärk laiendab haaret / Monika Puutsa

    Index Scriptorium Estoniae

    Puutsa, Monika

    2005-01-01

    Kuressaare Veevärk OÜ ja Veemaailm INC sõlmisid lepingu vee- ja kanalisatsioonitorustiku rajamiseks ja uuendamiseks linna 24 tänaval, mis on esimene etapp Saare maakonda hõlmavast Ühtekuuluvusfondi veemajanduse projektist. 80% ulatuses rahastab projekti EL

  12. [Nonstructural protein 1 of tick-borne encephalitis virus activates the expression of immunoproteasome subunits].

    Science.gov (United States)

    Kuzmenko, Y V; Starodubova, E S; Karganova, G G; Timofeev, A V; Karpov, V L

    2016-01-01

    The interaction of viral proteins with host cell components plays an important role in antiviral immune response. One of the key steps of antiviral defense is the formation of immunoproteasomes. The effect of nonstructural protein 1 (NS1) of tick-borne encephalitis virus on the immunoproteasome formation was studied. It was shown that cell expression of NS1 does not reduce the efficacy of the immunoproteasome generation in response to interferon-γ stimulation and even increases the content of the immunoproteasome subunits without the interferon-γ treatment. Thus, NS1 of tick-borne encephalitis virus activates, rather than blocks the mechanisms of immune defense in the cell.

  13. Chikungunya virus infection amongst the acute encephalitis syndrome cases in West Bengal, India

    Directory of Open Access Journals (Sweden)

    D Taraphdar

    2015-01-01

    Full Text Available Chikungunya virus (CHIKV infection from the acute encephalitis syndrome cases is an uncommon form and has been observed in the year 2010-11 from West Bengal, India. The case-1 and case-2 had the acute encephalitis syndrome; case-3 was of acute disseminated encephalomyelitis whereas the case-4 had the symptoms of meningo-encephalopathy with bulbar involvement. We are reporting four cases with neurological complications involving central nervous system (CNS due to CHIKV infection from this state for the first time. The virus has spread almost every districts of this state rapidly. At this stage, these cases are public health threat.

  14. Subclinical infection without encephalitis in mice following intranasal exposure to Nipah virus-Malaysia and Nipah virus-Bangladesh.

    Science.gov (United States)

    Dups, Johanna; Middleton, Deborah; Long, Fenella; Arkinstall, Rachel; Marsh, Glenn A; Wang, Lin-Fa

    2014-06-02

    Nipah virus and Hendra virus are closely related and following natural or experimental exposure induce similar clinical disease. In humans, encephalitis is the most serious outcome of infection and, hitherto, research into the pathogenesis of henipavirus encephalitis has been limited by the lack of a suitable model. Recently we reported a wild-type mouse model of Hendra virus (HeV) encephalitis that should facilitate detailed investigations of its neuropathogenesis, including mechanisms of disease recrudescence. In this study we investigated the possibility of developing a similar model of Nipah virus encephalitis. Aged and young adult wild type mice did not develop clinical disease including encephalitis following intranasal exposure to either the Malaysia (NiV-MY) or Bangladesh (NiV-BD) strains of Nipah virus. However viral RNA was detected in lung tissue of mice at euthanasia (21 days following exposure) accompanied by a non-neutralizing antibody response. In a subsequent time course trial this viral RNA was shown to be reflective of an earlier self-limiting and subclinical lower respiratory tract infection through successful virus re-isolation and antigen detection in lung. There was no evidence for viremia or infection of other organs, including brain. Mice develop a subclinical self-limiting lower respiratory tract infection but not encephalitis following intranasal exposure to NiV-BD or NiV-MY. These results contrast with those reported for HeV under similar exposure conditions in mice, demonstrating a significant biological difference in host clinical response to exposure with these viruses. This finding provides a new platform from which to explore the viral and/or host factors that determine the neuroinvasive ability of henipaviruses.

  15. Focal Coxsackie virus B5 encephalitis with synchronous seizure cluster and eruption: Infantile case.

    Science.gov (United States)

    Shiohama, Tadashi; Omata, Taku; Muta, Kaori; Kodama, Kazuo; Fujii, Katsunori; Shimojo, Naoki

    2016-05-01

    Enterovirus focal encephalitis is a rare clinical entity that is characterized by focal neurological signs including seizure, hemiparesis, hemichorea, and headache, which are mainly followed by rapid spontaneous improvement. We herein describe the case of a 9-month-old boy who developed Coxsackie virus B5 (CVB5) focal encephalitis with seizure clusters in the eruption stage of roseola infantum-like illness, which were followed by rapid improvement and benign outcome. Lumbar puncture indicated pleocytosis, and CVB5 infection in the cerebrospinal fluid was subsequently identified on genome sequencing and virus isolation. Magnetic resonance imaging and electroencephalography showed no abnormal findings at the acute stage or on 2 month follow up. Although the pathogenesis of enterovirus focal encephalitis currently remains unclear, the pure synchronism of seizure cluster and eruption in this case suggests the involvement of local vascular impairment as the underlying pathogenesis. © 2015 Japan Pediatric Society.

  16. Relation of genetic phylogeny and geographical distance of tick-borne encephalitis virus in central Europe

    NARCIS (Netherlands)

    Weidmann, M.; Ruzek, D.; Krivanec, K.; Zoeller, G.; Essbauer, S.; Pfeffer, M.; Zanotto, P. M. de A.; Hufert, F. T.; Dobler, G.

    Tick-borne encephalitis virus (TBEV) is the most important arboviral agent causing disease of the central nervous system in central Europe. In this study, 61 TBEV E gene sequences derived from 48 isolates from the Czech Republic, and four isolates and nine TBEV strains detected in ticks from

  17. Production of Japanese Encephalitis Virus Antigens in Plants Using Bamboo Mosaic Virus-Based Vector

    Directory of Open Access Journals (Sweden)

    Tsung-Hsien Chen

    2017-05-01

    Full Text Available Japanese encephalitis virus (JEV is among the major threats to public health in Asia. For disease control and prevention, the efficient production of safe and effective vaccines against JEV is in urgent need. In this study, we produced a plant-made JEV vaccine candidate using a chimeric virus particle (CVP strategy based on bamboo mosaic virus (BaMV for epitope presentation. The chimeric virus, designated BJ2A, was constructed by fusing JEV envelope protein domain III (EDIII at the N-terminus of BaMV coat protein, with an insertion of the foot-and-mouth disease virus 2A peptide to facilitate the production of both unfused and epitope-presenting for efficient assembly of the CVP vaccine candidate. The strategy allowed stable maintenance of the fusion construct over long-term serial passages in plants. Immuno-electron microscopy examination and immunization assays revealed that BJ2A is able to present the EDIII epitope on the surface of the CVPs, which stimulated effective neutralizing antibodies against JEV infection in mice. This study demonstrates the efficient production of an effective CVP vaccine candidate against JEV in plants by the BaMV-based epitope presentation system.

  18. Production of Japanese Encephalitis Virus Antigens in Plants Using Bamboo Mosaic Virus-Based Vector.

    Science.gov (United States)

    Chen, Tsung-Hsien; Hu, Chung-Chi; Liao, Jia-Teh; Lee, Yi-Ling; Huang, Ying-Wen; Lin, Na-Sheng; Lin, Yi-Ling; Hsu, Yau-Heiu

    2017-01-01

    Japanese encephalitis virus (JEV) is among the major threats to public health in Asia. For disease control and prevention, the efficient production of safe and effective vaccines against JEV is in urgent need. In this study, we produced a plant-made JEV vaccine candidate using a chimeric virus particle (CVP) strategy based on bamboo mosaic virus (BaMV) for epitope presentation. The chimeric virus, designated BJ2A, was constructed by fusing JEV envelope protein domain III (EDIII) at the N-terminus of BaMV coat protein, with an insertion of the foot-and-mouth disease virus 2A peptide to facilitate the production of both unfused and epitope-presenting for efficient assembly of the CVP vaccine candidate. The strategy allowed stable maintenance of the fusion construct over long-term serial passages in plants. Immuno-electron microscopy examination and immunization assays revealed that BJ2A is able to present the EDIII epitope on the surface of the CVPs, which stimulated effective neutralizing antibodies against JEV infection in mice. This study demonstrates the efficient production of an effective CVP vaccine candidate against JEV in plants by the BaMV-based epitope presentation system.

  19. Field Investigations of Winter Transmission of Eastern Equine Encephalitis Virus in Florida

    OpenAIRE

    Bingham, Andrea M.; Burkett-Cadena, Nathan D.; HASSAN, HASSAN K.; McClure, Christopher J.W.; Unnasch, Thomas R

    2014-01-01

    Studies investigating winter transmission of Eastern equine encephalitis virus (EEEV) were conducted in Hillsborough County, Florida. The virus was detected in Culiseta melanura and Anopheles quadrimaculatus in February 2012 and 2013, respectively. During the winter months, herons were the most important avian hosts for all mosquito species encountered. In collections carried out in the summer of 2011, blood meals taken from herons were still common, but less frequently encountered than in wi...

  20. [F-18]FHPG positron emission tomography for detection of herpes simplex virus (HSV) in experimental HSV encephalitis

    NARCIS (Netherlands)

    Buursma, AR; de Vries, EFJ; Garssen, J; Kegler, D; van Waarde, A; Schirm, J; Hospers, GAP; Mulder, NH; Vaalburg, W; Klein, HC

    Herpes simplex virus type 1 (HSV-1) is one of the most common causes of sporadic encephalitis. The initial clinical course of HSV encephalitis (HSE) is highly variable, and the infection may be rapidly fatal. For effective treatment with antiviral medication, an early diagnosis of HSE is crucial.

  1. Emergence or improved detection of Japanese encephalitis virus in the Himalayan highlands?

    Science.gov (United States)

    Baylis, Matthew; Barker, Christopher M; Caminade, Cyril; Joshi, Bhoj R; Pant, Ganesh R; Rayamajhi, Ajit; Reisen, William K; Impoinvil, Daniel E

    2016-04-01

    The emergence of Japanese encephalitis virus (JEV) in the Himalayan highlands is of significant veterinary and public health concern and may be related to climate warming and anthropogenic landscape change, or simply improved surveillance. To investigate this phenomenon, a One Health approach focusing on the phylogeography of JEV, the distribution and abundance of the mosquito vectors, and seroprevalence in humans and animal reservoirs would be useful to understand the epidemiology of Japanese encephalitis in highland areas. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

  2. Molecular identification of Saint Louis encephalitis virus genotype IV in Colombia

    Directory of Open Access Journals (Sweden)

    Richard Hoyos-López

    2015-09-01

    Full Text Available Saint Louis encephalitis virus (SLEV is a member of the Japanese-encephalitis virus serocomplex of the genus Flavivirus. SLEV is broadly distributed in the Americas and the Caribbean Islands, where it is usually transmitted by mosquitoes of the genus Culex and primarily to birds and mammalian-hosts. Humans are occasionally infected by the virus and are dead-end hosts. SLEV causes encephalitis in temperate regions, while in tropical regions of the Americas, several human cases and a wide biological diversity of SLEV-strains have been reported. The phylogenetic analysis of the envelope (E protein genes indicated eight-genotypes of SLEV with geographic overlap. The present paper describes the genotyping of two SLEV viruses detected in mosquito-pools collected in northern Colombia (department of Cordoba. We used reverse transcription-polymerase chain reaction to amplify a fragment of theE-gene to confirm the virus identity and completeE-gene sequencing for phylogenetic analysis and genotyping of the two-SLEV viruses found circulating in Córdoba. This is the first report of SLEV genotype IV in Colombia (Córdoba in mosquitoes from a region of human inhabitation, implicating the risk of human disease due to SLEV infection. Physicians should consider SLEV as a possible aetiology for undiagnosed febrile and neurologic syndromes among their patients who report exposure to mosquito-bites.

  3. Delayed IFN response differentiates replication of West Nile virus and Japanese encephalitis virus in human neuroblastoma and glioblastoma cells.

    Science.gov (United States)

    Takamatsu, Yuki; Uchida, Leo; Morita, Kouichi

    2015-08-01

    West Nile virus (WNV) and Japanese encephalitis virus (JEV) are important causes of human encephalitis cases, which result in a high mortality ratio and neurological sequelae after recovery. Understanding the mechanism of neuropathogenicity in these viral infections is important for the development of specific antiviral therapy. Here, we focused on human-derived neuronal and glial cells to understand the cellular responses against WNV and JEV infection. It was demonstrated that early IFN-β induction regulated virus replication in glioblastoma tbl98G cells, whereas delayed IFN-β induction resulted in efficient virus replication in neuroblastoma SK-N-SH cells. Moreover, the concealing of viral dsRNA in the intracellular membrane resulted in the delayed IFN response in SK-N-SH cells. These results, which showed different IFN responses between human neuronal and glial cells after WNV or JEV infection, are expected to contribute to our understanding of the molecular mechanisms for neuropathology in these viral infections.

  4. Respiratory syncytial virus-related encephalitis: magnetic resonance imaging findings with diffusion-weighted study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Arim; Suh, Sang-il; Seol, Hae-Young [Korea University College of Medicine, Department of Radiology, Korea University Guro Hospital, Seoul (Korea, Republic of); Son, Gyu-Ri; Lee, Nam-Joon [Korea University College of Medicine, Department of Radiology, Korea University Anam Hospital, Seoul (Korea, Republic of); Lee, Young Hen; Seo, Hyung Suk [Korea University College of Medicine, Department of Radiology, Korea University Ansan Hospital, Gyeonggi-do (Korea, Republic of); Eun, Baik-Lin [Korea University College of Medicine, Department of Pediatrics, Korea University Guro Hospital, Seoul (Korea, Republic of)

    2014-02-15

    Respiratory syncytial virus (RSV) is a common pathogen causing acute respiratory infection in children. Herein, we describe the incidence and clinical and magnetic resonance imaging (MRI) findings of RSV-related encephalitis, a major neurological complication of RSV infection. We retrospectively reviewed the medical records and imaging findings of the patients over the past 7 years who are admitted to our medical center and are tested positive for RSV-RNA by reverse transcriptase PCR. In total, 3,856 patients were diagnosed with RSV bronchiolitis, and 28 of them underwent brain MRI for the evaluation of neurologic symptoms; 8 of these 28 patients had positive imaging findings. Five of these 8 patients were excluded because of non-RSV-related pathologies, such as subdural hemorrhage, brain volume loss due to status epilepticus, periventricular leukomalacia, preexisting ventriculomegaly, and hypoxic brain injury. The incidence of RSV-related encephalitis was as follows: 3/3,856 (0.08 %) of the patients are positive for RSV RNA, 3/28 (10.7 %) of the patient underwent brain MRI for neurological symptom, and 3/8 (37.5 %) of patients revealed abnormal MR findings. The imaging findings were suggestive of patterns of rhombenmesencephalitis, encephalitis with acute disseminated encephalomyelitis, and limbic encephalitis. They demonstrated no diffusion abnormality on diffusion-weighted image and symptom improvement on the follow-up study. Encephalitis with RSV bronchiolitis occurs rarely. However, on brain MRI performed upon suspicion of neurologic involvement, RSV encephalitis is not infrequently observed among the abnormal MR findings and may mimic other viral and limbic encephalitis. Physicians should be aware of this entity to ensure proper diagnosis and neurologic care of RSV-positive patients. (orig.)

  5. Epidemiological modeling and risk analysis of Venezuelan Equine Encephalitis in the human population of Coastal Chiapas, Mexico in 2007-2009

    Science.gov (United States)

    Analysis of 101 febrile illness patients sero positive for Venezuelan equine encephalitis (VEEV) was carried out in a retrospective study along 18 municipalities and endemic VEEV pacific coastal regions of the State of Chiapas in southern Mexico. Geographic information systems (GIS), satellite imag...

  6. First Isolation of West Nile virus from a patient with encephalitis in the United States.

    Science.gov (United States)

    Huang, Cinnia; Slater, Brett; Rudd, Robert; Parchuri, Nandakishore; Hull, Rene; Dupuis, Michelle; Hindenburg, Alexander

    2002-12-01

    West Nile virus (WNV) was isolated from a patient who developed encephalitis while undergoing treatment with CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine [Oncovin], predisone) and rituximab for a non-Hodgkin B-cell lymphoma. Both standard reverse transcription-polymerase chain reaction (RT-PCR) and Taqman RT-PCR established the diagnosis of WNV infection from cerebrospinal fluid (CSF). Several whole blood samples and one serum sample underwent further testing. CSF and serum samples were negative for WNV antibody; however, all samples were positive by both RT-PCR assays. Infectious virus was recovered from a blood sample, and its identity was confirmed by using a WNV-specific immunofluorescence assay. The complete WNV genomes determined from CSF and from the virus isolate adapted from cell culture were the same. The results represent the first complete WNV genome sequence obtained directly from human CSF and the first time that infectious WNV has been recovered from a patient with encephalitis in North America.

  7. Tick-borne encephalitis virus - a review of an emerging zoonosis.

    Science.gov (United States)

    Mansfield, K L; Johnson, N; Phipps, L P; Stephenson, J R; Fooks, A R; Solomon, T

    2009-08-01

    During the last 30 years, there has been a continued increase in human cases of tick-borne encephalitis (TBE) in Europe, a disease caused by tick-borne encephalitis virus (TBEV). TBEV is endemic in an area ranging from northern China and Japan, through far-eastern Russia to Europe, and is maintained in cycles involving Ixodid ticks (Ixodes ricinus and Ixodes persulcatus) and wild vertebrate hosts. The virus causes a potentially fatal neurological infection, with thousands of cases reported annually throughout Europe. TBE has a significant mortality rate depending upon the strain of virus or may cause long-term neurological/neuropsychiatric sequelae in people affected. In this review, we comprehensively reviewed TBEV, its epidemiology and pathogenesis, the clinical manifestations of TBE, along with vaccination and prevention. We also discuss the factors which may have influenced an apparent increase in the number of reported human cases each year, despite the availability of effective vaccines.

  8. Estimating the burden of Japanese encephalitis virus and other encephalitides in countries of the mekong region.

    Directory of Open Access Journals (Sweden)

    Arnaud Tarantola

    Full Text Available Diverse aetiologies of viral and bacterial encephalitis are widely recognized as significant yet neglected public health issues in the Mekong region. A robust analysis of the corresponding health burden is lacking. We retrieved 75 articles on encephalitis in the region published in English or in French from 1965 through 2011. Review of available data demonstrated that they are sparse and often derived from hospital-based studies with significant recruitment bias. Almost half (35 of 75 of articles were on Japanese encephalitis virus (JEV alone or associated with dengue. In the Western Pacific region the WHO reported 30,000-50,000 annual JEV cases (15,000 deaths between 1966 and 1996 and 4,633 cases (200 deaths in 2008, a decline likely related to the introduction of JEV vaccination in China, Vietnam, or Thailand since the 1980s. Data on dengue, scrub typhus and rabies encephalitis, among other aetiologies, are also reviewed and discussed. Countries of the Mekong region are undergoing profound demographic, economic and ecological change. As the epidemiological aspects of Japanese encephalitis (JE are transformed by vaccination in some countries, highly integrated expert collaborative research and objective data are needed to identify and prioritize the human health, animal health and economic burden due to JE and other pathogens associated with encephalitides.

  9. Estimating the Burden of Japanese Encephalitis Virus and Other Encephalitides in Countries of the Mekong Region

    Science.gov (United States)

    Tarantola, Arnaud; Goutard, Flavie; Newton, Paul; de Lamballerie, Xavier; Lortholary, Olivier; Cappelle, Julien; Buchy, Philippe

    2014-01-01

    Diverse aetiologies of viral and bacterial encephalitis are widely recognized as significant yet neglected public health issues in the Mekong region. A robust analysis of the corresponding health burden is lacking. We retrieved 75 articles on encephalitis in the region published in English or in French from 1965 through 2011. Review of available data demonstrated that they are sparse and often derived from hospital-based studies with significant recruitment bias. Almost half (35 of 75) of articles were on Japanese encephalitis virus (JEV) alone or associated with dengue. In the Western Pacific region the WHO reported 30,000–50,000 annual JEV cases (15,000 deaths) between 1966 and 1996 and 4,633 cases (200 deaths) in 2008, a decline likely related to the introduction of JEV vaccination in China, Vietnam, or Thailand since the 1980s. Data on dengue, scrub typhus and rabies encephalitis, among other aetiologies, are also reviewed and discussed. Countries of the Mekong region are undergoing profound demographic, economic and ecological change. As the epidemiological aspects of Japanese encephalitis (JE) are transformed by vaccination in some countries, highly integrated expert collaborative research and objective data are needed to identify and prioritize the human health, animal health and economic burden due to JE and other pathogens associated with encephalitides. PMID:24498443

  10. BK virus encephalitis: case report, review of the literature, and description of a novel treatment modality.

    Science.gov (United States)

    Chittick, Paul; Williamson, John C; Ohl, Christopher A

    2013-09-01

    To describe a case of BK virus encephalitis with attempted direct antiviral therapy, review the reported cases of BK virus in the central nervous system, and report the novel use of intravenous cimetidine in place of oral probenecid to minimize the toxicities of intravenous cidofovir. A 36-year-old male with acute myelomonocytic leukemia and subsequent myelodysplastic syndrome underwent allogeneic hematopoietic stem cell transplant. His course was complicated by severe graft-versus-host disease involving his skin and gastrointestinal tract. Five weeks after transplantation, he developed fever and confusion. Magnetic resonance imaging was suggestive of limbic encephalitis and cerebrospinal fluid tested positive for BK virus. Therapy with intravenous cidofovir was thought to be indicated. Although probenecid is commonly used to minimize the toxicities of cidofovir, the patient's severe graft-versus-host disease raised concerns about absorption of oral medications. Based on animal models and pharmacokinetic data, intravenous cimetidine was used in place of oral probenecid. Despite these therapies, the patient's mental status did not improve. He developed progressive organ system failure, and care was ultimately withdrawn. BK virus is increasingly described as a cause of encephalitis. The majority of reported cases have occurred in immunocompromised patients and have generally had a poor outcome. This case describes attempted antiviral therapy using cidofovir, the antiviral agent used most frequently in other syndromes due to BK virus. Intravenous cimetidine is a novel modality used to minimize ocular and renal toxicities frequently seen with cidofovir, and we believe this warrants further investigation. BK virus may be a cause of encephalitis in immunocompromised hosts, and cidofovir represents a possible treatment option. Intravenous cimetidine can be considered to minimize toxicities associated with cidofovir use in patients unable to tolerate or absorb oral

  11. Nonstructural Protein L* Species Specificity Supports a Mouse Origin for Vilyuisk Human Encephalitis Virus.

    Science.gov (United States)

    Drappier, Melissa; Opperdoes, Fred R; Michiels, Thomas

    2017-07-15

    Vilyuisk human encephalitis virus (VHEV) is a picornavirus related to Theiler's murine encephalomyelitis virus (TMEV). VHEV was isolated from human material passaged in mice. Whether this VHEV is of human or mouse origin is therefore unclear. We took advantage of the species-specific activity of the nonstructural L* protein of theiloviruses to track the origin of TMEV isolates. TMEV L* inhibits RNase L, the effector enzyme of the interferon pathway. By using coimmunoprecipitation and functional RNase L assays, the species specificity of RNase L antagonism was tested for L* from mouse (DA) and rat (RTV-1) TMEV strains as well as for VHEV. Coimmunoprecipitation and functional assay data confirmed the species specificity of L* activity and showed that L* from rat strain RTV-1 inhibited rat but not mouse or human RNase L. Next, we showed that the VHEV L* protein was phylogenetically related to L* of mouse viruses and that it failed to inhibit human RNase L but readily antagonized mouse RNase L, unambiguously showing the mouse origin of VHEV. IMPORTANCE Defining the natural host of a virus can be a thorny issue, especially when the virus was isolated only once or when the isolation story is complex. The species Theilovirus includes Theiler's murine encephalomyelitis virus (TMEV), infecting mice and rats, and Saffold virus (SAFV), infecting humans. One TMEV strain, Vilyuisk human encephalitis virus (VHEV), however, was isolated from mice that were inoculated with cerebrospinal fluid of a patient presenting with chronic encephalitis. It is therefore unclear whether VHEV was derived from the human sample or from the inoculated mouse. The L* protein encoded by TMEV inhibits RNase L, a cellular enzyme involved in innate immunity, in a species-specific manner. Using binding and functional assays, we show that this species specificity even allows discrimination between TMEV strains of mouse and of rat origins. The VHEV L* protein clearly inhibited mouse but not human RNase L

  12. Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management.

    Science.gov (United States)

    Bradshaw, Michael J; Venkatesan, Arun

    2016-07-01

    Herpetic infections have plagued humanity for thousands of years, but only recently have advances in antiviral medications and supportive treatments equipped physicians to combat the most severe manifestations of disease. Prompt recognition and treatment can be life-saving in the care of patients with herpes simplex-1 virus encephalitis, the most commonly identified cause of sporadic encephalitis worldwide. Clinicians should be able to recognize the clinical signs and symptoms of the infection and familiarize themselves with a rational diagnostic approach and therapeutic modalities, as early recognition and treatment are key to improving outcomes. Clinicians should also be vigilant for the development of acute complications, including cerebral edema and status epilepticus, as well as chronic complications, including the development of autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor and other neuronal cell surface and synaptic epitopes. Herein, we review the pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults, including a discussion of the most common complications and their treatment. While great progress has been made in the treatment of this life-threatening infection, a majority of patients will not return to their previous neurologic baseline, indicating the need for further research efforts aimed at improving the long-term sequelae.

  13. Demographics of natural oral infection of mosquitos by Venezuelan equine encephalitis virus.

    Science.gov (United States)

    Gutiérrez, Serafín; Thébaud, Gaël; Smith, Darci R; Kenney, Joan L; Weaver, Scott C

    2015-04-01

    The within-host diversity of virus populations can be drastically limited during between-host transmission, with primary infection of hosts representing a major constraint to diversity maintenance. However, there is an extreme paucity of quantitative data on the demographic changes experienced by virus populations during primary infection. Here, the multiplicity of cellular infection (MOI) and population bottlenecks were quantified during primary mosquito infection by Venezuelan equine encephalitis virus, an arbovirus causing neurological disease in humans and equids. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. Delayed Diagnosis of Tuberculous Meningitis Misdiagnosed as Herpes Simplex Virus-1 Encephalitis With the FilmArray Syndromic Polymerase Chain Reaction Panel.

    Science.gov (United States)

    Gomez, Carlos A; Pinsky, Benjamin A; Liu, Anne; Banaei, Niaz

    2017-01-01

    The FilmArray meningitis/encephalitis (ME) panel is a novel syndromic, nucleic acid amplification test for diagnosis of acute meningitis and encephalitis. Emerging data on its performance are concerning for false-positive results. We present a case of tuberculous meningitis misdiagnosed as herpes simplex virus-1 encephalitis with the FilmArray ME panel. Strategies to mitigate erroneous results are discussed.

  15. A novel cell-based assay to measure activity of Venezuelan equine encephalitis virus nsP2 protease

    Energy Technology Data Exchange (ETDEWEB)

    Campos-Gomez, Javier; Ahmad, Fahim; Rodriguez, Efrain; Saeed, Mohammad F., E-mail: saeed@southernresearch.org

    2016-09-15

    The encephalitic alphaviruses encode nsP2 protease (nsP2pro), which because of its vital role in virus replication, represents an attractive target for therapeutic intervention. To facilitate the discovery of nsP2 inhibitors we have developed a novel assay for quantitative measurement of nsP2pro activity in a cell-based format. The assay is based on a substrate fusion protein consisting of eGFP and Gaussia luciferase (Gluc) linked together by a small peptide containing a VEEV nsp2pro cleavage sequence. The expression of the substrate protein in cells along with recombinant nsP2pro results in cleavage of the substrate protein resulting in extracellular release of free Gluc. The Gluc activity in supernatants corresponds to intracellular nsP2pro-mediated substrate cleavage; thus, providing a simple and convenient way to quantify nsP2pro activity. Here, we demonstrate potential utility of the assay in identification of nsP2pro inhibitors, as well as in investigations related to molecular characterization of nsP2pro. - Highlights: • A novel cell-based assay to measure VEEV nsP2 protease activity was developed. • Assay utility was demonstrated for antiviral screening. • .The assay also proved to be useful in basic mechanistic studies of nsP2 protease.

  16. Evaluation of reverse-transcriptase PCR as a diagnostic tool to confirm Japanese encephalitis virus infection.

    Science.gov (United States)

    Saxena, Vandana; Mishra, Virendra K; Dhole, Tapan N

    2009-04-01

    Japanese encephalitis (JE) is a serious central nervous system infection and major public health problem in several countries of Southeast Asia including India. This study evaluated the use of IgM ELISA and reverse-transcriptase (RT)-PCR in blood and cerebrospinal fluid (CSF) samples from acute encephalitis patients for the detection of Japanese encephalitis virus (JEV). Forty-four children suffering from acute encephalitis were enrolled, and 36 were selected from whom both CSF and serum samples were available. Twenty-two of the 36 CSF samples were positive for JEV by IgM ELISA and all were negative by RT-PCR. Twenty-three of the 36 serum samples were positive by IgM ELISA while 28 were positive by RT-PCR. Total positivity for JEV infection in CSF and serum samples was 66.7% (24/36) and 83.3% (30/36) respectively by one or both tests. The overall positivity for JEV infection was 86.1% (31/36). We suggest that the use of RT-PCR in serum samples during the early days of JEV infection may be helpful in confirming diagnosis in those cases which are negative for JEV-specific IgM antibodies in both serum and CSF samples.

  17. Viperin restricts Zika virus and tick-borne encephalitis virus replication by targeting NS3 for proteasomal degradation.

    Science.gov (United States)

    Panayiotou, Christakis; Lindqvist, Richard; Kurhade, Chaitanya; Vonderstein, Kirstin; Pasto, Jenny; Edlund, Karin; Upadhyay, Arunkumar S; Överby, Anna K

    2018-01-10

    Flaviviruses are arthropod-borne viruses that constitute a major global health problem, with millions of human infections annually. Their pathogenesis ranges from mild illness to severe manifestations such as hemorrhagic fever and fatal encephalitis. Type I interferons (IFNs) are induced in response to viral infection, and stimulate the expression of interferon-stimulated genes (ISGs), including that encoding viperin (virus-inhibitory protein, endoplasmic reticulum-associated, IFN-inducible), which shows antiviral activity against a broad spectrum of viruses including several flaviviruses. Here we describe a novel antiviral mechanism exerted by viperin against two prominent flaviviruses, tick-borne encephalitis virus (TBEV) and Zika virus (ZIKV). Viperin was found to interact and co-localize with the structural proteins pre-membrane (prM) and envelope (E) of TBEV, as well as the non-structural (NS) proteins NS2A, NS2B, and NS3. Interestingly, viperin expression reduced the NS3 protein level, and the stability of the other interacting viral proteins, but only in the presence of NS3. We also found that although viperin interacted with NS3 of mosquito-borne flaviviruses (ZIKV, Japanese encephalitis virus, and yellow fever virus), only ZIKV was sensitive to the antiviral effect of viperin. This sensitivity correlated with viperin's ability to induce proteasome-dependent degradation of NS3. ZIKV and TBEV replication was rescued completely when NS3 was overexpressed, suggesting that the viral NS3 is the specific target of viperin. In summary, we present here a novel antiviral mechanism of viperin that is selective for specific viruses in the genus Flavivirus, affording the possibility of new drug targets that can be used for therapeutic intervention.ImportanceFlaviviruses are a group of enveloped RNA viruses that cause severe diseases in humans and animals worldwide, but no antiviral treatment is yet available. Viperin, a host protein produced in response to infection

  18. Post Tick-Borne Encephalitis Virus Vaccination Narcolepsy with Cataplexy.

    Science.gov (United States)

    Hidalgo, Hildegard; Kallweit, Ulf; Mathis, Johannes; Bassetti, Claudio L

    2016-10-01

    Narcolepsy with cataplexy (NC) is a chronic neurological disorder thought to result from an altered immune response based on a genetic predisposition coupled with environmental factors. Pandemrix vaccination has been reported to increase the risk of narcolepsy. We aimed at identifying other vaccines associated with the onset of narcolepsy. Case series and retrospective database study. We identified four cases of NC following a tick-borne encephalitis (TBE) vaccination with FSME Immun. Additional four cases could be detected in the database of the Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines in Germany. Our findings implicate TBE vaccination as a potential additional environmental factor for the development of NC and add additional evidence for an immunological mechanism in the pathogenesis of the disease.

  19. Replicon Particles of Venezuelan Equine Encephalitis Virus as a Reductionist Murine Model for Encephalitis▿

    Science.gov (United States)

    Schäfer, Alexandra; Whitmore, Alan C.; Konopka, Jennifer L.; Johnston, Robert E.

    2009-01-01

    Venezuelan equine encephalitis virus (VEE) replicon particles (VRP) were used to model the initial phase of VEE-induced encephalitis in the mouse brain. VRP can target and infect cells as VEE, but VRP do not propagate beyond the first infected cell due to the absence of the structural genes. Direct intracranial inoculation of VRP into mice induced acute encephalitis with signs similar to the neuronal phase of wild-type VEE infection and other models of virus-induced encephalitis. Using the previously established VRP-mRNP tagging system, a new method to distinguish the host responses in infected cells from those in uninfected bystander cell populations, we detected a robust and rapid innate immune response in the central nervous system (CNS) by infected neurons and uninfected bystander cells. Moreover, this innate immune response in the CNS compromised blood-brain barrier integrity, created an inflammatory response, and directed an adaptive immune response characterized by proliferation and activation of microglia cells and infiltration of inflammatory monocytes, in addition to CD4+ and CD8+ T lymphocytes. Taken together, these data suggest that a naïve CNS has an intrinsic potential to induce an innate immune response that could be crucial to the outcome of the infection by determining the composition and dynamics of the adaptive immune response. Furthermore, these results establish a model for neurotropic virus infection to identify host and viral factors that contribute to invasion of the brain, the mechanism(s) whereby the adaptive immune response can clear the infection, and the role of the host innate response in these processes. PMID:19225006

  20. [Serological evidence of St. Louis encephalitis virus circulation in birds from Buenos Aires City, Argentina].

    Science.gov (United States)

    Beltrán, Fernando J; Díaz, Luis A; Konigheim, Brenda; Molina, José; Beaudoin, Juan B; Contigiani, Marta; Spinsanti, Lorena I

    2015-01-01

    Our goal was to determine the presence of neutralizing antibodies against St. Louis encephalitis virus (SLEV) and West Nile virus (WNV) in sera of wild and domestic birds from Buenos Aires City, Argentina. From October 2012 to April 2013, 180 samples were collected and processed by the microneutralization technique. A 7.2% of the sampled birds were seropositive for SLEV, while no seropositive birds for WNV were detected. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Increasing evidence of tick-borne encephalitis (TBE) virus transmission, the Netherlands, June 2016.

    Science.gov (United States)

    Weststrate, Adriaan Cg; Knapen, Daan; Laverman, Gozewijn D; Schot, Bart; Prick, Jan Jw; Spit, Silke A; Reimerink, Johan; Rockx, Barry; Geeraedts, Felix

    2017-03-16

    We present a case of endemic tick-borne encephalitis (TBE) occurring in June 2016 in the eastern part of the Netherlands in an area where a strain of TBE virus, genetically different from the common TBE virus strains in Europe, was reported in ticks in 2016. With the start of the tick season in spring, this second autochthonous Dutch TBE case should remind physicians to consider the possibility of endemic TBE in patients with respective symptoms. This article is copyright of The Authors, 2017.

  2. Affinity (tropism) of caprine arthritis encephalitis virus for brain cells

    African Journals Online (AJOL)

    STORAGESEVER

    2008-11-19

    Nov 19, 2008 ... while wobbling gait with ataxia are the main features in goat kids. The virus was first identified in the USA (Cork et al., 1974). To-date, eight .... Nucleotide sequence and transcriptional analysis of molecular clones of CAEV which generate infectious virus. Virology, 179: 347-364. Watkins BA, Dorn HH, Kelly ...

  3. European Aedes albopictus and Culex pipiens Are Competent Vectors for Japanese Encephalitis Virus.

    Directory of Open Access Journals (Sweden)

    Mélissanne de Wispelaere

    2017-01-01

    Full Text Available Japanese encephalitis virus (JEV is the causative agent of Japanese encephalitis, the leading cause of viral encephalitis in Asia. JEV transmission cycle involves mosquitoes and vertebrate hosts. The detection of JEV RNA in a pool of Culex pipiens caught in 2010 in Italy raised the concern of a putative emergence of the virus in Europe. We aimed to study the vector competence of European mosquito populations, such as Cx. pipiens and Aedes albopictus for JEV genotypes 3 and 5.After oral feeding on an infectious blood meal, mosquitoes were dissected at various times post-virus exposure. We found that the peak for JEV infection and transmission was between 11 and 13 days post-virus exposure. We observed a faster dissemination of both JEV genotypes in Ae. albopictus mosquitoes, when compared with Cx. pipiens mosquitoes. We also dissected salivary glands and collected saliva from infected mosquitoes and showed that Ae. albopictus mosquitoes transmitted JEV earlier than Cx. pipiens. The virus collected from Ae. albopictus and Cx. pipiens saliva was competent at causing pathogenesis in a mouse model for JEV infection. Using this model, we found that mosquito saliva or salivary glands did not enhance the severity of the disease.In this study, we demonstrated that European populations of Ae. albopictus and Cx. pipiens were efficient vectors for JEV transmission. Susceptible vertebrate species that develop high viremia are an obligatory part of the JEV transmission cycle. This study highlights the need to investigate the susceptibility of potential JEV reservoir hosts in Europe, notably amongst swine populations and local water birds.

  4. European Aedes albopictus and Culex pipiens Are Competent Vectors for Japanese Encephalitis Virus.

    Science.gov (United States)

    de Wispelaere, Mélissanne; Desprès, Philippe; Choumet, Valérie

    2017-01-01

    Japanese encephalitis virus (JEV) is the causative agent of Japanese encephalitis, the leading cause of viral encephalitis in Asia. JEV transmission cycle involves mosquitoes and vertebrate hosts. The detection of JEV RNA in a pool of Culex pipiens caught in 2010 in Italy raised the concern of a putative emergence of the virus in Europe. We aimed to study the vector competence of European mosquito populations, such as Cx. pipiens and Aedes albopictus for JEV genotypes 3 and 5. After oral feeding on an infectious blood meal, mosquitoes were dissected at various times post-virus exposure. We found that the peak for JEV infection and transmission was between 11 and 13 days post-virus exposure. We observed a faster dissemination of both JEV genotypes in Ae. albopictus mosquitoes, when compared with Cx. pipiens mosquitoes. We also dissected salivary glands and collected saliva from infected mosquitoes and showed that Ae. albopictus mosquitoes transmitted JEV earlier than Cx. pipiens. The virus collected from Ae. albopictus and Cx. pipiens saliva was competent at causing pathogenesis in a mouse model for JEV infection. Using this model, we found that mosquito saliva or salivary glands did not enhance the severity of the disease. In this study, we demonstrated that European populations of Ae. albopictus and Cx. pipiens were efficient vectors for JEV transmission. Susceptible vertebrate species that develop high viremia are an obligatory part of the JEV transmission cycle. This study highlights the need to investigate the susceptibility of potential JEV reservoir hosts in Europe, notably amongst swine populations and local water birds.

  5. Low Protective Efficacy of the Current Japanese Encephalitis Vaccine against the Emerging Genotype 5 Japanese Encephalitis Virus.

    Science.gov (United States)

    Cao, Lei; Fu, Shihong; Gao, Xiaoyan; Li, Minghua; Cui, Shiheng; Li, Xiaolong; Cao, Yuxi; Lei, Wenwen; Lu, Zhi; He, Ying; Wang, Huanyu; Yan, Jinghua; Gao, George Fu; Liang, Guodong

    2016-05-01

    The current Japanese encephalitis (JE) vaccine derived from G3 JE virus (JEV) can induce protective immunity against G1-G4 JEV genotypes. However, protective efficacy against the emerging G5 genotype has not been reported. Using in vitro and in vivo tests, biological phenotype and cross-immunoreactions were compared between G3 JEV and G5 JEV (wild strains). The PRNT90 method was used to detect neutralizing antibodies against different genotypes of JEV in JE vaccine-immunized subjects and JE patients. In JE vaccine-immunized mice, the lethal challenge protection rates against G3 and G5 JEV wild strains were 100% and 50%, respectively. The seroconversion rates (SCRs) of virus antibodies against G3 and G5 JEV among vaccinated healthy subjects were 100% and 35%, respectively. All clinically identified JE patients showed high levels of G3 JEV neutralizing antibodies (≥1:10-1280) with positive serum geometric mean titers (GMTs) of 43.2, while for G5 JEV, neutralizing antibody conversion rates were only 64% with positive serum GMTs of 11.14. Moreover, the positive rate of JEV neutralizing antibodies against G5 JEV in pediatric patients was lower than in adults. Low levels of neutralizing/protective antibodies induced by the current JE vaccine, based on the G3 genotype, were observed against the emerging G5 JEV genotype. Our results demonstrate the need for more detailed studies to reevaluate whether or not the apparent emergence of G5 JEV can be attributed to failure of the current vaccine to induce appropriate immune protectivity against this genotype of JEV.

  6. Detection of West Nile virus and tick-borne encephalitis virus in birds in Slovakia, using a universal primer set.

    Science.gov (United States)

    Csank, Tomáš; Bhide, Katarína; Bencúrová, Elena; Dolinská, Saskia; Drzewnioková, Petra; Major, Peter; Korytár, Ľuboš; Bocková, Eva; Bhide, Mangesh; Pistl, Juraj

    2016-06-01

    West Nile virus (WNV) is a mosquito-borne neurotropic pathogen that presents a major public health concern. Information on WNV prevalence and circulation in Slovakia is insufficient. Oral and cloacal swabs and bird brain samples were tested for flavivirus RNA by RT-PCR using newly designed generic primers. The species designation was confirmed by sequencing. WNV was detected in swab and brain samples, whereas one brain sample was positive for tick-borne encephalitis virus (TBEV). The WNV sequences clustered with lineages 1 and 2. These results confirm the circulation of WNV in birds in Slovakia and emphasize the risk of infection of humans and horses.

  7. Antiviral Activity of Baicalein and Quercetin against the Japanese Encephalitis Virus

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    Jefree Johari

    2012-12-01

    Full Text Available Japanese encephalitis (JE, a mosquito-borne viral disease, is endemic to the entire east and southeast Asia, and some other parts of the world. Currently, there is no effective therapeutic available for JE; therefore, finding the effective antiviral agent against JEV replication is crucial. In the present study, the in vitro antiviral activity of baicalein and quercetin, two purportedly antiviral bioflavonoids, was evaluated against Japanese encephalitis virus (JEV replication in Vero cells. Anti-JEV activities of these compounds were examined on different stages of JEV replication cycle. The effects of the compounds on virus replication were determined by foci forming unit reduction assay (FFURA and quantitative RT-PCR. Baicalein showed potent antiviral activity with IC50 = 14.28 µg/mL when it was introduced to the Vero cells after adsorption of JEV. Quercetin exhibited weak anti-JEV effects with IC50 = 212.1 µg/mL when the JEV infected cells were treated with the compound after virus adsorption. However, baicalein exhibited significant effect against JEV adsorption with IC50 = 7.27 µg/mL while quercetin did not show any anti-adsorption activity. Baicalein also exhibited direct extracellular virucidal activity on JEV with IC50 = 3.44 µg/mL. However, results of quantitative RT-PCR experiments confirmed the findings from FFURA. This study demonstrated that baicalein should be considered as an appropriate candidate for further investigations, such as the study of molecular and cellular mechanism(s of action and in vivo evaluation for the development of an effective antiviral compound against Japanese encephalitis virus.

  8. CLEC5A regulates Japanese encephalitis virus-induced neuroinflammation and lethality.

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    Szu-Ting Chen

    Full Text Available CLEC5A/MDL-1, a member of the myeloid C-type lectin family expressed on macrophages and neutrophils, is critical for dengue virus (DV-induced hemorrhagic fever and shock syndrome in Stat1⁻/⁻ mice and ConA-treated wild type mice. However, whether CLEC5A is involved in the pathogenesis of viral encephalitis has not yet been investigated. To investigate the role of CLEC5A to regulate JEV-induced neuroinflammation, antagonistic anti-CLEC5A mAb and CLEC5A-deficient mice were generated. We find that Japanese encephalitis virus (JEV directly interacts with CLEC5A and induces DAP12 phosphorylation in macrophages. In addition, JEV activates macrophages to secrete proinflammatory cytokines and chemokines, which are dramatically reduced in JEV-infected Clec5a⁻/⁻ macrophages. Although blockade of CLEC5A cannot inhibit JEV infection of neurons and astrocytes, anti-CLEC5A mAb inhibits JEV-induced proinflammatory cytokine release from microglia and prevents bystander damage to neuronal cells. Moreover, JEV causes blood-brain barrier (BBB disintegrity and lethality in STAT1-deficient (Stat1⁻/⁻ mice, whereas peripheral administration of anti-CLEC5A mAb reduces infiltration of virus-harboring leukocytes into the central nervous system (CNS, restores BBB integrity, attenuates neuroinflammation, and protects mice from JEV-induced lethality. Moreover, all surviving mice develop protective humoral and cellular immunity against JEV infection. These observations demonstrate the critical role of CLEC5A in the pathogenesis of Japanese encephalitis, and identify CLEC5A as a target for the development of new treatments to reduce virus-induced brain damage.

  9. Cortical cholinergic decline parallels the progression of Borna virus encephalitis

    NARCIS (Netherlands)

    Gies, U; Gorcs, TJ; Mulder, J; Planz, O; Stitz, L; Bilzer, T; Luiten, PGM; Harkany, T; Görcs, Tamás J.

    2001-01-01

    Borna disease virus (BDV)-induced meningoencephalitis is associated with the dysfunction of the cholinergic system. Temporal development of this cholinergic decline during pre-encephalitic and encephalitic stages of BDV infection remains however elusive. Changes in choline acetyltransferase (ChAT)

  10. Development of a Genetically Engineered Venezuelan Equine Encephalitis Virus Vaccine

    Science.gov (United States)

    1991-04-15

    contributes to the virulence of TRD virus. To determine the contribution which the TRD 5’-noncoding region makes to virulence and the synergism between... chloramphenicol acetyl transferase gene by DEAE-dextran medicated DNA transfection coupled with a dimethyl sulfoxide or glycerol shock treatment. Nucleic Acids

  11. Changing Trend of T lymphocytes in Mouse Spleen after Japanese Encephalitis Virus Infection

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    Yan-fang Sun§, Chang-qin Gu§, Rong Jiang , Jing Ye, Yong-mao Li, Hua-zhen Liu , Hui Song and Ke-mei Peng*

    2011-10-01

    Full Text Available Japanese encephalitis is caused by Japanese encephalitis viruses (JEV with neurotropism. As one of the most important immune organ, spleen is directly involved in immune response against JEV. However, little research about JEV infection process in spleen has been reported. In this study, immunopathological changes in mouse spleen were analyzed every other day after subcutaneous injection of mice with JEV wild-type strain P3 by immunohistochemistry assay. Immunohistochemistry analysis demonstrated that the number of T lymphocytes was reduced from 0 to 3 DPI, increased from 3 to 7 DPI, and reduced again from 7 to 10 DPI. In addition, neurological dysfunction appeared at 6 DPI. These results suggested that spleen of mice suffered incontrovertible damages in influence of JEV infection. It can also be deduced that the cellular immunity took the crucial part in the first phase of transient viremia against JEV. Moreover, immune response was activated after the immune-depressed period in the first phase of viremia and neurological dysfunction appeared when cellular immunity was activated. Taking together, our research showed distinct immunopathological changes in mice after JEV infection, which enriched our understanding of Japanese encephalitis immunopathogenesis.

  12. Antiviral Activity of Isatis indigotica Extract and Its Derived Indirubin against Japanese Encephalitis Virus

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    Shu-Jen Chang

    2012-01-01

    Full Text Available Isatis indigotica is widely used in Chinese Traditional Medicine for clinical treatment of virus infection, tumor, and inflammation, yet its antiviral activities remain unclear. This study probed antiviral activity of I. indigotica extract and its marker compounds against Japanese encephalitis virus (JEV. I. indigotica methanol extract, indigo, and indirubin proved less cytotoxic than other components, showing inhibitory effect (concentration-dependent on JEV replication in vitro. Time-of-addition experiments proved the extract, indigo, and indirubin with potent antiviral effect by pretreatment (before infection or simultaneous treatment (during infection, but not posttreatment (after entry. Antiviral action of these agents showed correlation with blocking virus attachment and exhibited potent virucidal activity. In particular, indirubin had strong protective ability in a mouse model with lethal JEV challenge. The study could yield anti-JEV agents.

  13. STUDIES ON THE BIOCHEMICAL, BIOPHYSICAL, AND IMMUNOGENIC PROPERTIES OF JAPANESE B TYPE ENCEPHALITIS VIRUS AND VACCINES.

    Science.gov (United States)

    Duffy, C E; Stanley, W M

    1945-11-30

    Studies on the biochemical, biophysical, and immunogenic properties of Japanese B type encephalitis virus and vaccines have been made in order to determine whether a purified vaccine suitable for human use could be obtained by means of differential centrifugation of extracts of infected mouse brains. Studies were also made on extracts of normal mouse brains, it was found that extracts of normal as well as of infected mouse brains contained fairly large amounts of several components of high molecular weight. Components having sedimentation constants near 5 and 40 Svedberg units were found in extracts of infected brains. However the rates of sedimentation of the different components were so similar that it was found impossible, from a practical standpoint, to secure a vaccine consisting largely of virus by means of differential centrifugation. It was also found that a considerable portion of virus was lost or destroyed in the centrifugation process so that it was impossible to secure an effective degree of concentration of immunogenic potency. Although vaccines possessing about twice the immunogenic potency of the starting material were obtained, it was concluded that it was not practical to purify and concentrate Japanese B type encephalitis virus in infected mouse brain extracts by means of differential centrifugation for the production of a vaccine on a large scale. The optimum pH stability range of Japanese B type encephalitis virus activity was found to be near pH 8.5. The virus is inactivated fairly rapidly at pH 7 and very rapidly at more acid reactions. The virus is inactivated rapidly near pH 10. Extracts of infected mouse brains with buffers near pH 8 containing disodium phosphate were found to possess slightly higher titers than saline extracts near pH 7. However vaccines prepared from such extracts were found to possess essentially the same immunogenic potency, hence, although extraction at the more alkaline reaction may perhaps remove more active virus

  14. Safety and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®) in children.

    Science.gov (United States)

    Chokephaibulkit, K; Houillon, G; Feroldi, E; Bouckenooghe, A

    2016-01-01

    JE-CV (IMOJEV®, Sanofi Pasteur, France) is a live attenuated virus vaccine constructed by inserting coding sequences of the prM and E structural proteins of the Japanese encephalitis SA14-14-2 virus into the genome of yellow fever 17D virus. Primary immunization with JE-CV requires a single dose of the vaccine. This article reviews clinical trials of JE-CV in children aged up to 6 years conducted in countries across South-East Asia. Strong and persistent antibody responses were observed after single primary and booster doses, with 97% of children seroprotected up to five years after booster vaccination. Models of long-term antibody persistence predict a median duration of protection of approximately 30 years after a booster dose. The safety and reactogenicity profiles of JE-CV primary and booster doses are comparable to other widely used childhood vaccines.

  15. Seroconversion for west Nile and St. Louis encephalitis viruses among sentinel horses in Colombia

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    Salim Mattar

    2011-12-01

    Full Text Available We prospectively sampled flavivirus-naïve horses in northern Colombia to detect West Nile virus (WNV and St. Louis encephalitis virus (SLEV seroconversion events, which would indicate the current circulation of these viruses. Overall, 331 (34.1% of the 971 horses screened were positive for past infection with flaviviruses upon initial sampling in July 2006. During the 12-month study from July 2006-June 2007, 33 WNV seroconversions and 14 SLEV seroconversions were detected, most of which occurred in the department of Bolivar. The seroconversion rates of horses in Bolivar for the period of March-June 2007 reached 12.4% for WNV and 6.7% for SLEV. These results comprise the first serologic evidence of SLEV circulation in Colombia. None of the horses sampled developed symptoms of encephalitis within three years of initial sampling. Using seroconversions in sentinel horses, we demonstrated an active circulation of WNV and SLEV in northern Colombia, particularly in the department of Bolivar. The absence of WNV-attributed equine or human disease in Colombia and elsewhere in the Caribbean Basin remains a topic of debate and speculation.

  16. Intensive Circulation of Japanese Encephalitis Virus in Peri-urban Sentinel Pigs near Phnom Penh, Cambodia.

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    Julien Cappelle

    2016-12-01

    Full Text Available Despite the increased use of vaccination in several Asian countries, Japanese Encephalitis (JE remains the most important cause of viral encephalitis in Asia in humans with an estimated 68,000 cases annually. Considered a rural disease occurring mainly in paddy-field dominated landscapes where pigs are amplifying hosts, JE may nevertheless circulate in a wider range of environment given the diversity of its potential hosts and vectors. The main objective of this study was to assess the intensity of JE transmission to pigs in a peri-urban environment in the outskirt of Phnom Penh, Cambodia. We estimated the force of JE infection in two cohorts of 15 sentinel pigs by fitting a generalised linear model on seroprevalence monitoring data observed during two four-month periods in 2014. Our results provide evidence for intensive circulation of JE virus in a periurban area near Phnom Penh, the capital and most populated city of Cambodia. Understanding JE virus transmission in different environments is important for planning JE virus control in the long term and is also an interesting model to study the complexity of vector-borne diseases. Collecting quantitative data such as the force of infection will help calibrate epidemiological model that can be used to better understand complex vector-borne disease epidemiological cycles.

  17. Intensive Circulation of Japanese Encephalitis Virus in Peri-urban Sentinel Pigs near Phnom Penh, Cambodia.

    Science.gov (United States)

    Cappelle, Julien; Duong, Veasna; Pring, Long; Kong, Lida; Yakovleff, Maud; Prasetyo, Didot Budi; Peng, Borin; Choeung, Rithy; Duboz, Raphaël; Ong, Sivuth; Sorn, San; Dussart, Philippe; Tarantola, Arnaud; Buchy, Philippe; Chevalier, Véronique

    2016-12-01

    Despite the increased use of vaccination in several Asian countries, Japanese Encephalitis (JE) remains the most important cause of viral encephalitis in Asia in humans with an estimated 68,000 cases annually. Considered a rural disease occurring mainly in paddy-field dominated landscapes where pigs are amplifying hosts, JE may nevertheless circulate in a wider range of environment given the diversity of its potential hosts and vectors. The main objective of this study was to assess the intensity of JE transmission to pigs in a peri-urban environment in the outskirt of Phnom Penh, Cambodia. We estimated the force of JE infection in two cohorts of 15 sentinel pigs by fitting a generalised linear model on seroprevalence monitoring data observed during two four-month periods in 2014. Our results provide evidence for intensive circulation of JE virus in a periurban area near Phnom Penh, the capital and most populated city of Cambodia. Understanding JE virus transmission in different environments is important for planning JE virus control in the long term and is also an interesting model to study the complexity of vector-borne diseases. Collecting quantitative data such as the force of infection will help calibrate epidemiological model that can be used to better understand complex vector-borne disease epidemiological cycles.

  18. Seroprevalence of caprine artritis-encephalitis virus in goats of Lima region, Peru

    OpenAIRE

    Gomes M., Angel; Laboratorio de Microbiología y Parasitología Veterinaria, Facultad de Medicina Veterinaria, Universidad Nacional Mayor de San Marcos, Lima; Rivera G., Hermelinda; Laboratorio de Microbiología y Parasitología Veterinaria, Facultad de Medicina Veterinaria, Universidad Nacional Mayor de San Marcos, Lima Perú.; Ramírez V., Mercy; Laboratorio de Microbiología y Parasitología Veterinaria, Facultad de Medicina Veterinaria, Universidad Nacional Mayor de San Marcos, Lima; Cardozo Z., Imelda; Servicio Nacional de Sanidad Animal (SENASA), Lima; Manchego S., Alberto; Laboratorio de Microbiología y Parasitología Veterinaria, Facultad de Medicina Veterinaria, Universidad Nacional Mayor de San Marcos, Lima

    2015-01-01

    The seroprevalence of caprine artritis-encephalitis virus (CAEV) in four provinces of Lima Region, Peru was determined in 381 goat serum samples (325 females and 56 males) older than 12 months from 89 flocks reared under intensive (n=3), semiextensive (n=49) and transhumant (n=46) production systems. The detection of antibodies against CAEV was done by a competitive-inhibition ELISA test. The overall seroprevalence of CAEV was 0.26 ± 0.09% (1/381). The seropositive goat belonged to one flock ...

  19. BK virus encephalitis with thrombotic microangiopathy in an allogeneic hematopoietic stem cell transplant recipient.

    Science.gov (United States)

    Lopes da Silva, R; Ferreira, I; Teixeira, G; Cordeiro, D; Mafra, M; Costa, I; Bravo Marques, J M; Abecasis, M

    2011-04-01

    BK virus (BKV) infection occurs most often in immunocompromised hosts, in the setting of renal or bone marrow transplantation. Hemorrhagic cystitis is the commonest manifestation but in recent years infections in other organ systems have been reported. We report an unusual case of biopsy-proven BKV encephalitis in a hematopoietic stem cell transplant patient who subsequently developed thrombotic microangiopathy. As far as we know, this is the first report of such an association in a transplant patient. © 2010 John Wiley & Sons A/S.

  20. Siberian subtype tick-borne encephalitis virus in Ixodes ricinus in a newly emerged focus, Finland.

    Science.gov (United States)

    Jääskeläinen, Anu; Tonteri, Elina; Pieninkeroinen, Ilkka; Sironen, Tarja; Voutilainen, Liina; Kuusi, Markku; Vaheri, Antti; Vapalahti, Olli

    2016-02-01

    The first tick-borne encephalitis (TBE) cases in Kotka, Finland appeared in 2010. Altogether ten human cases have been diagnosed by 2014. Four had long-lasting sequelae. We collected 195 Ixodes ricinus ticks, nine rodents, and eleven shrews from the archipelago of Kotka in 2011. Three Siberian subtype TBE virus (TBEV) strains were isolated from the ticks and three mammals were positive for TBEV antibodies. The archipelago of Kotka is a newly emerged TBE focus of Siberian subtype TBEV circulating notably in I. ricinus. The patients had on average longer hospitalization than reported for the European subtype infection. Copyright © 2015 Elsevier GmbH. All rights reserved.

  1. Parasitic Cowbirds have increased immunity to West Nile and other mosquitoborne encephalitis viruses

    Science.gov (United States)

    Reisen, W.K.; Hahn, D.C.

    2006-01-01

    The rapid geographic spread of West Nile Virus [WNV, Flaviviridae, Flavivirus] across the United States has stimulated interest in comparative host infection studies of avian species to delineate competent reservoir hosts critical for viral amplification. Striking taxonomic differences in avian susceptibility have been noted, offering the opportunity to strategically select species on the basis of life history traits to examine aspects of pathogen virulence or host immunity. We hypothesized that avian brood parasites would show increased resistance to pathogens compared to related taxa, because they have been exposed in their evolutionary history to a wide array of infectious organisms from their different parenting species. The Brown-headed Cowbird (Molothrus ater) is a generalist brood parasite that parasitizes 200+ North American species. Elevated exposure to other species? parasites may have created an unusual degree of pathogen resistance. We compared the relative susceptibility of adult cowbirds to three closely-related non-parasitic species, Red-winged blackbirds, Tricolored blackbirds and Brewer?s blackbirds, to invading NY99 strain of WNV that is highly virulent for many passeriform birds. Previously we had experimentally infected these species with two North American mosquitoborne encephalitis viruses, western equine encephalomyelitis virus [WEEV, Togaviridae, Alphavirus] and St. Louis encephalitis virus [SLEV, Flaviviridae, Flavivirus]. Our results showed that cowbirds exhibited significantly lower viremia responses against all three viruses as well as after co-infection with both WEEV and WNV than did the three related, non-parasitic species. These data supported our hypothesis and indicated that cowbirds were more resistant to infection to both native and introduced viruses.

  2. Yellow fever/Japanese encephalitis chimeric viruses: construction and biological properties.

    Science.gov (United States)

    Chambers, T J; Nestorowicz, A; Mason, P W; Rice, C M

    1999-04-01

    A system has been developed for generating chimeric yellow fever/Japanese encephalitis (YF/JE) viruses from cDNA templates encoding the structural proteins prM and E of JE virus within the backbone of a molecular clone of the YF17D strain. Chimeric viruses incorporating the proteins of two JE strains, SA14-14-2 (human vaccine strain) and JE Nakayama (JE-N [virulent mouse brain-passaged strain]), were studied in cell culture and laboratory mice. The JE envelope protein (E) retained antigenic and biological properties when expressed with its prM protein together with the YF capsid; however, viable chimeric viruses incorporating the entire JE structural region (C-prM-E) could not be obtained. YF/JE(prM-E) chimeric viruses grew efficiently in cells of vertebrate or mosquito origin compared to the parental viruses. The YF/JE SA14-14-2 virus was unable to kill young adult mice by intracerebral challenge, even at doses of 10(6) PFU. In contrast, the YF/JE-N virus was neurovirulent, but the phenotype resembled parental YF virus rather than JE-N. Ten predicted amino acid differences distinguish the JE E proteins of the two chimeric viruses, therefore implicating one or more residues as virus-specific determinants of mouse neurovirulence in this chimeric system. This study indicates the feasibility of expressing protective antigens of JE virus in the context of a live, attenuated flavivirus vaccine strain (YF17D) and also establishes a genetic system for investigating the molecular basis for neurovirulence determinants encoded within the JE E protein.

  3. Neutralizing activities of human immunoglobulin derived from donors in Japan against mosquito-borne flaviviruses, Japanese encephalitis virus, West Nile virus, and dengue virus

    Directory of Open Access Journals (Sweden)

    Yunoki M

    2016-07-01

    Full Text Available Mikihiro Yunoki,1-3 Takeshi Kurosu,2 Ritsuko Kubota Koketsu,2,4 Kazuo Takahashi,5 Yoshinobu Okuno,4 Kazuyoshi Ikuta2,4 1Research and Development Division, Japan Blood Products Organization, Tokyo, 2Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, 3Pathogenic Risk Evaluation, Graduate School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, 4Research and Development Division, The Research Foundation for Microbial Diseases of Osaka University, Kagawa, 5Osaka Prefectural Institute of Public Health, Osaka, Japan Abstract: Japanese encephalitis virus (JEV, West Nile virus (WNV, and dengue virus (DenV are causal agents of Japanese encephalitis, West Nile fever, and dengue fever, respectively. JEV is considered to be indigenized and widespread in Japan, whereas WNV and DenV are not indigenized in Japan. Globulin products seem to reflect the status of the donor population according to antivirus neutralization activity. However, the anti-JEV, -WNV, and -DenV neutralization activities of globulin products derived from donors in Japan have not been clarified. Furthermore, potential candidates for the development of an effective immunotherapeutic drug for encephalitis caused by JEV, WNV, or DenV have also not been identified. Therefore, the aim of this study was to determine the overall status of the donor population in Japan based on globulin products by evaluating anti-JEV, -WNV, and -DenV neutralizing activities of intravenous immunoglobulin. Overall, intravenous immunoglobulin products showed stable neutralizing activity against JEV but showed no or only weak activity against WNV or DenV. These results suggest that the epidemiological level against WNV and DenV in the donor population of Japan is still low, suggesting that these viruses are not yet indigenized. In addition, JEV vaccinations and/or infections in the donor population do not induce a cross-reactive antibody against WNV. Keywords

  4. Encephalitis due to emerging viruses: CNS innate immunity and potential therapeutic targets.

    Science.gov (United States)

    Denizot, M; Neal, J W; Gasque, P

    2012-07-01

    The emerging viruses represent a group of pathogens that are intimately connected to a diverse range of animal vectors. The recent escalation of air travel climate change and urbanization has meant humans will have increased risk of contacting these pathogens resulting in serious CNS infections. Many RNA viruses enter the CNS by evading the BBB due to axonal transport from the periphery. The systemic adaptive and CNS innate immune systems express pattern recognition receptors PRR (TLRs, RiG-1 and MDA-5) that detect viral nucleic acids and initiate host antiviral response. However, several emerging viruses (West Nile Fever, Influenza A, Enterovirus 71 Ebola) are recognized and internalized by host cell receptors (TLR, MMR, DC-SIGN, CD162 and Scavenger receptor B) and escape immuno surveillance by the host systemic and innate immune systems. Many RNA viruses express viral proteins WNF (E protein), Influenza A (NS1), EV71 (protein 3C), Rabies (Glycoprotein), Ebola proteins (VP24 and VP 35) that inhibit the host cell anti-virus Interferon type I response promoting virus replication and encephalitis. The therapeutic use of RNA interference methodologies to silence gene expression of viral peptides and treat emerging virus infection of the CNS is discussed. Copyright © 2012. Published by Elsevier Ltd.

  5. Antibodies to H5 subtype avian influenza virus and Japanese encephalitis virus in northern pintails (Anas acuta) sampled in Japan

    Science.gov (United States)

    Ramey, Andy M.; Spackman, Erica; Yeh, Jung-Yong; Fujita, Go; Konishi, Kan; Reed, John A.; Wilcox, Benjamin R.; Brown, Justin D.; Stallknecht, David E.

    2013-01-01

    Blood samples from 105 northern pintails (Anas acuta) captured on Hokkaido, Japan were tested for antibodies to avian influenza virus (AIV), Japanese encephalitis virus (JEV), and West Nile virus (WNV) to assess possible involvement of this species in the spread of economically important and potentially zoonotic pathogens. Antibodies to AIV were detected in 64 of 105 samples (61%). Of the 64 positives, 95% and 81% inhibited agglutination of two different H5 AIV antigens (H5N1 and H5N9), respectively. Antibodies to JEV and WNV were detected in five (5%) and none of the samples, respectively. Results provide evidence for prior exposure of migrating northern pintails to H5 AIV which couldhave implications for viral shedding and disease occurrence. Results also provide evidence for limited involvement of this species in the transmission and spread of flaviviruses during spring migration.

  6. Review of climate, landscape, and viral genetics as drivers of the Japanese encephalitis virus ecology.

    Directory of Open Access Journals (Sweden)

    Guillaume Le Flohic

    Full Text Available The Japanese encephalitis virus (JEV, an arthropod-born Flavivirus, is the major cause of viral encephalitis, responsible for 10,000-15,000 deaths each year, yet is a neglected tropical disease. Since the JEV distribution area has been large and continuously extending toward new Asian and Australasian regions, it is considered an emerging and reemerging pathogen. Despite large effective immunization campaigns, Japanese encephalitis remains a disease of global health concern. JEV zoonotic transmission cycles may be either wild or domestic: the first involves wading birds as wild amplifying hosts; the second involves pigs as the main domestic amplifying hosts. Culex mosquito species, especially Cx. tritaeniorhynchus, are the main competent vectors. Although five JEV genotypes circulate, neither clear-cut genotype-phenotype relationship nor clear variations in genotype fitness to hosts or vectors have been identified. Instead, the molecular epidemiology appears highly dependent on vectors, hosts' biology, and on a set of environmental factors. At global scale, climate, land cover, and land use, otherwise strongly dependent on human activities, affect the abundance of JEV vectors, and of wild and domestic hosts. Chiefly, the increase of rice-cultivated surface, intensively used by wading birds, and of pig production in Asia has provided a high availability of resources to mosquito vectors, enhancing the JEV maintenance, amplification, and transmission. At fine scale, the characteristics (density, size, spatial arrangement of three landscape elements (paddy fields, pig farms, human habitations facilitate or impede movement of vectors, then determine how the JEV interacts with hosts and vectors and ultimately the infection risk to humans. If the JEV is introduced in a favorable landscape, either by live infected animals or by vectors, then the virus can emerge and become a major threat for human health. Multidisciplinary research is essential to shed

  7. Thiosemicarbazones and Phthalyl-Thiazoles compounds exert antiviral activity against yellow fever virus and Saint Louis encephalitis virus.

    Science.gov (United States)

    Pacca, Carolina Colombelli; Marques, Rafael Elias; Espindola, José Wanderlan P; Filho, Gevânio B O Oliveira; Leite, Ana Cristina Lima; Teixeira, Mauro Martins; Nogueira, Mauricio L

    2017-03-01

    Arboviruses, arthropod-borneviruses, are frequency associated to human outbreak and represent a serious health problem. The genus Flavivirus, such as Yellow Fever Virus (YFV) and Saint Louis Encephalitis Virus (SLEV), are important pathogens with high morbidity and mortality worldwide. In Brazil, YFV is maintained in sylvatic cycle, but many cases are notified annually, despite the efficiency of vaccine. SLEV causes an acute encephalitis and is widely distributed in the Americas. There is no specific antiviral drugs for these viruses, only supporting treatment that can alleviate symptoms and prevent complications. Here, we evaluated the potential anti-YFV and SLEV activity of a series of thiosemicarbazones and phthalyl-thiazoles. Plaque reduction assay, flow cytometry, immunofluorescence and cellular viability were used to test the compounds in vitro. Treated cells showed efficient inhibition of the viral replication at concentrations that presented minimal toxicity to cells. The assays showed that phthalyl-thiazole and phenoxymethyl-thiosemicarbazone reduced 60% of YFV replication and 75% of SLEV replication. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Japanese encephalitis virus disrupts blood-brain barrier and modulates apoptosis proteins in THBMEC cells.

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    Al-Obaidi, Mazen M Jamil; Bahadoran, Azadeh; Har, Lee Sau; Mui, Wang Seok; Rajarajeswaran, Jayakumar; Zandi, Keivan; Manikam, Rishya; Sekaran, Shamala Devi

    2017-04-02

    Japanese encephalitis (JE) is a neurotropic flavivirus that causes inflammation in central nervous system (CNS), neuronal death and also compromises the structural and functional integrity of the blood-brain barrier (BBB). The aim of this study was to evaluate the BBB disruption and apoptotic process in Japanese encephalitis virus (JEV)-infected transfected human brain microvascular endothelial cells (THBMECs). THBMECs were overlaid by JEV with different MOIs (0.5, 1.0, 5.0 and 10.0) and monitored by electrical cell-substrate impedance sensing (ECIS) in a real-time manner in order to observe the barrier function of THBMECs. Additionally, the level of 43 apoptotic proteins was quantified in the virally infected cells with different MOIs at 24h post infection. Infection of THBMEC with JEV induced an acute reduction in transendothelial electrical resistance (TEER) after viral infection. Also, significant up-regulation of Bax, BID, Fas and Fasl and down-regulation of IGFBP-2, BID, p27 and p53 were observed in JEV infected THBMECs with 0.5 and 10 MOIs compared to uninfected cells. Hence, the permeability of THBMECs is compromised during the JEV infection. In addition high viral load of the virus has the potential to subvert the host cell apoptosis to optimize the course of viral infection through deactivation of pro-apoptotic proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Molecular epidemiology of Japanese encephalitis virus in mosquitoes in Taiwan during 2005-2012.

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    Chien-Ling Su

    2014-10-01

    Full Text Available Japanese encephalitis (JE is a mosquito-borne zoonotic disease caused by the Japanese encephalitis virus (JEV. Pigs and water birds are the main amplifying and maintenance hosts of the virus. In this study, we conducted a JEV survey in mosquitoes captured in pig farms and water bird wetland habitats in Taiwan during 2005 to 2012. A total of 102,633 mosquitoes were collected. Culex tritaeniorhynchus was the most common mosquito species found in the pig farms and wetlands. Among the 26 mosquito species collected, 11 tested positive for JEV by RT-PCR, including Cx. tritaeniorhynchus, Cx. annulus, Anopheles sinensis, Armigeres subalbatus, and Cx. fuscocephala. Among those testing positive, Cx. tritaeniorhynchus was the predominant vector species for the transmission of JEV genotypes I and III in Taiwan. The JEV infection rate was significantly higher in the mosquitoes from the pig farms than those from the wetlands. A phylogenetic analysis of the JEV envelope gene sequences isolated from the captured mosquitoes demonstrated that the predominant JEV genotype has shifted from genotype III to genotype I (GI, providing evidence for transmission cycle maintenance and multiple introductions of the GI strains in Taiwan during 2008 to 2012. This study demonstrates the intense JEV transmission activity in Taiwan, highlights the importance of JE vaccination for controlling the epidemic, and provides valuable information for the assessment of the vaccine's efficacy.

  10. Cellular DDX3 regulates Japanese encephalitis virus replication by interacting with viral un-translated regions.

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    Li, Chen; Ge, Ling-ling; Li, Peng-peng; Wang, Yue; Dai, Juan-juan; Sun, Ming-xia; Huang, Li; Shen, Zhi-qiang; Hu, Xiao-chun; Ishag, Hassan; Mao, Xiang

    2014-01-20

    Japanese encephalitis virus is one of the most common causes for epidemic viral encephalitis in humans and animals. Herein we demonstrated that cellular helicase DDX3 is involved in JEV replication. DDX3 knockdown inhibits JEV replication. The helicase activity of DDX3 is crucial for JEV replication. GST-pulldown and co-immunoprecipitation experiments demonstrated that DDX3 could interact with JEV non-structural proteins 3 and 5. Co-immunoprecipitation and confocal microscopy analysis confirmed that DDX3 interacts and colocalizes with these viral proteins and viral RNA during the infection. We determined that DDX3 binds to JEV 5' and 3' un-translated regions. We used a JEV-replicon system to demonstrate that DDX3 positively regulates viral RNA translation, which might affect viral RNA replication at the late stage of virus infection. Collectively, we identified that DDX3 is necessary for JEV infection, suggesting that DDX3 might be a novel target to design new antiviral agents against JEV or other flavivirus infections. © 2013 Published by Elsevier Inc.

  11. Molecular Epidemiology of Japanese Encephalitis Virus in Mosquitoes in Taiwan during 2005–2012

    Science.gov (United States)

    Su, Chien-Ling; Yang, Cheng-Fen; Teng, Hwa-Jen; Lu, Liang-Chen; Lin, Cheo; Tsai, Kun-Hsien; Chen, Yu-Yu; Chen, Li-Yu; Chang, Shu-Fen; Shu, Pei-Yun

    2014-01-01

    Japanese encephalitis (JE) is a mosquito-borne zoonotic disease caused by the Japanese encephalitis virus (JEV). Pigs and water birds are the main amplifying and maintenance hosts of the virus. In this study, we conducted a JEV survey in mosquitoes captured in pig farms and water bird wetland habitats in Taiwan during 2005 to 2012. A total of 102,633 mosquitoes were collected. Culex tritaeniorhynchus was the most common mosquito species found in the pig farms and wetlands. Among the 26 mosquito species collected, 11 tested positive for JEV by RT-PCR, including Cx. tritaeniorhynchus, Cx. annulus, Anopheles sinensis, Armigeres subalbatus, and Cx. fuscocephala. Among those testing positive, Cx. tritaeniorhynchus was the predominant vector species for the transmission of JEV genotypes I and III in Taiwan. The JEV infection rate was significantly higher in the mosquitoes from the pig farms than those from the wetlands. A phylogenetic analysis of the JEV envelope gene sequences isolated from the captured mosquitoes demonstrated that the predominant JEV genotype has shifted from genotype III to genotype I (GI), providing evidence for transmission cycle maintenance and multiple introductions of the GI strains in Taiwan during 2008 to 2012. This study demonstrates the intense JEV transmission activity in Taiwan, highlights the importance of JE vaccination for controlling the epidemic, and provides valuable information for the assessment of the vaccine's efficacy. PMID:25275652

  12. Field investigations of winter transmission of eastern equine encephalitis virus in Florida.

    Science.gov (United States)

    Bingham, Andrea M; Burkett-Cadena, Nathan D; Hassan, Hassan K; McClure, Christopher J W; Unnasch, Thomas R

    2014-10-01

    Studies investigating winter transmission of Eastern equine encephalitis virus (EEEV) were conducted in Hillsborough County, Florida. The virus was detected in Culiseta melanura and Anopheles quadrimaculatus in February 2012 and 2013, respectively. During the winter months, herons were the most important avian hosts for all mosquito species encountered. In collections carried out in the summer of 2011, blood meals taken from herons were still common, but less frequently encountered than in winter, with an increased frequency of mammalian- and reptile-derived meals observed in the summer. Four wading bird species (Black-crowned Night Heron [Nycticorax nycticorax], Yellow-crowned Night Heron [Nyctanassa violacea], Anhinga [Anhinga anhinga], and Great Blue Heron [Ardea herodias]) were most frequently fed upon by Cs. melanura and Culex erraticus, suggesting that these species may participate in maintaining EEEV during the winter in Florida. © The American Society of Tropical Medicine and Hygiene.

  13. Flaviviruses, an expanding threat in public health: focus on Dengue, West Nile, and Japanese encephalitis virus

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    Daep, Carlo Amorin; Muñoz-Jordán, Jorge L.; Eugenin, Eliseo Alberto

    2014-01-01

    The flaviviruses Dengue, West Nile, and Japanese encephalitis represent three major mosquito-borne viruses worldwide. These pathogens impact the lives of millions of individuals and potentially could affect non-endemic areas already colonized by mosquito vectors. Unintentional transport of infected vectors (Aedes and Culex sp), traveling within endemic areas, rapid adaptation of the insects into new geographic locations, climate change, and lack of medical surveillance have greatly contributed to the increase in flaviviral infections worldwide. The mechanisms by which flaviviruses alter the immune and the central nervous system have only recently been examined despite the alarming number of infections, related deaths, and increasing global distribution. In this review, we will discuss the expansion of the geographic areas affected by flaviviruses, the potential threats to previously unaffected countries, the mechanisms of pathogenesis, and the potential therapeutic interventions to limit the devastating consequences of these viruses. PMID:25287260

  14. Flaviviruses, an expanding threat in public health: focus on dengue, West Nile, and Japanese encephalitis virus.

    Science.gov (United States)

    Daep, Carlo Amorin; Muñoz-Jordán, Jorge L; Eugenin, Eliseo Alberto

    2014-12-01

    The flaviviruses dengue, West Nile, and Japanese encephalitis represent three major mosquito-borne viruses worldwide. These pathogens impact the lives of millions of individuals and potentially could affect non-endemic areas already colonized by mosquito vectors. Unintentional transport of infected vectors (Aedes and Culex spp.), traveling within endemic areas, rapid adaptation of the insects into new geographic locations, climate change, and lack of medical surveillance have greatly contributed to the increase in flaviviral infections worldwide. The mechanisms by which flaviviruses alter the immune and the central nervous system have only recently been examined despite the alarming number of infections, related deaths, and increasing global distribution. In this review, we will discuss the expansion of the geographic areas affected by flaviviruses, the potential threats to previously unaffected countries, the mechanisms of pathogenesis, and the potential therapeutic interventions to limit the devastating consequences of these viruses.

  15. Caveolin-1-mediated Japanese encephalitis virus entry requires a two-step regulation of actin reorganization.

    Science.gov (United States)

    Xu, Qingqiang; Cao, Mingmei; Song, Hongyuan; Chen, Shenglin; Qian, Xijing; Zhao, Ping; Ren, Hao; Tang, Hailin; Wang, Yan; Wei, Youheng; Zhu, Yongzhe; Qi, Zhongtian

    2016-10-01

    To investigate the detailed mechanism of Japanese encephalitis virus (JEV) cell entry. Utilize a siRNA library targeting cellular membrane trafficking genes to identify key molecules that mediate JEV entry into human neuronal cells. JEV enters human neuronal cells by caveolin-1-mediated endocytosis, which depends on a two-step regulation of actin cytoskeleton remodeling triggered by RhoA and Rac1: RhoA activation promoted the phosphorylation of caveolin-1, and then Rac1 activation facilitated caveolin-associated viral internalization. Specifically, virus attachment activates the EGFR-PI3K signaling pathway, thereby leading to RhoA activation. This work provides a detailed picture of the entry route and intricate cellular events following the entry of JEV into human neuronal cells, and promotes a better understanding of JEV entry.

  16. Delayed Diagnosis of Tuberculous Meningitis Misdiagnosed as Herpes Simplex Virus-1 Encephalitis With the FilmArray Syndromic Polymerase Chain Reaction Panel

    OpenAIRE

    Gomez, Carlos A.; Pinsky, Benjamin A.; Liu, Anne; Banaei, Niaz

    2016-01-01

    Abstract The FilmArray meningitis/encephalitis (ME) panel is a novel syndromic, nucleic acid amplification test for diagnosis of acute meningitis and encephalitis. Emerging data on its performance are concerning for false-positive results. We present a case of tuberculous meningitis misdiagnosed as herpes simplex virus-1 encephalitis with the FilmArray ME panel. Strategies to mitigate erroneous results are discussed.

  17. Isolation and full-genome sequences of Japanese encephalitis virus genotype I strains from Cambodian human patients, mosquitoes and pigs.

    Science.gov (United States)

    Duong, Veasna; Choeung, Rithy; Gorman, Christopher; Laurent, Denis; Crabol, Yoann; Mey, Channa; Peng, Borin; Di Francesco, Juliette; Hul, Vibol; Sothy, Heng; Santy, Ky; Richner, Beat; Pommier, Jean-David; Sorn, San; Chevalier, Véronique; Buchy, Philippe; de Lamballerie, Xavier; Cappelle, Julien; Horwood, Paul Francis; Dussart, Philippe

    2017-09-01

    Japanese encephalitis remains the most important cause of viral encephalitis in humans in several southeast Asian countries, including Cambodia, causing at least 65 000 cases of encephalitis per year. This vector-borne viral zoonosis - caused by Japanese encephalitis virus (JEV) - is considered to be a rural disease and is transmitted by mosquitoes, with birds and pigs being the natural reservoirs, while humans are accidental hosts. In this study we report the first two JEV isolations in Cambodia from human encephalitis cases from two studies on the aetiology of central nervous system disease, conducted at the two major paediatric hospitals in the country. We also report JEV isolation from Culextritaeniorhynchus mosquitoes and from pig samples collected in two farms, located in peri-urban and rural areas. Out of 11 reverse-transcription polymerase chain reaction-positive original samples, we generated full-genome sequences from 5 JEV isolates. Five additional partial sequences of the JEV NS3 gene from viruses detected in five pigs and one complete coding sequence of the envelope gene of a strain identified in a pig were generated. Phylogenetic analyses revealed that JEV detected in Cambodia belonged to genotype I and clustered in two clades: genotype I-a, mainly comprising strains from Thailand, and genotype I-b, comprising strains from Vietnam that dispersed northwards to China. Finally, in this study, we provide proof that the sequenced JEV strains circulate between pigs, Culex tritaeniorhynchus and humans in the Phnom Penh vicinity.

  18. Partially neutralizing potency against emerging genotype I virus among children received formalin-inactivated Japanese encephalitis virus vaccine.

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    Yi-Chin Fan

    Full Text Available BACKGROUND: Genotype I (GI Japanese encephalitis virus (JEV that replaced GIII virus has become the dominant circulating virus in Asia. Currently, all registered live and inactivated JEV vaccines are derived from genotype III viruses. In Taiwan, the compulsory JEV vaccination policy recommends that children receives four doses of formalin-inactivated Nakayama (GIII JEV vaccine. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the influence of genotype replacement on the post-vaccination viral neutralizing ability by GIII and GI viruses, the small panel of vaccinated-children serum specimens was assembled, and the reciprocal 50% plaque-reduction neutralizing antibody titers (PRNT(50 were measured against Nakayama vaccine strain, CJN GIII human brain isolate and TC2009-1 GI mosquito isolate. The seropositivity rate (PRNT(50 ≥ 1:10 and geometric mean titers (GMT against the TC2009-1 virus were the lowest among the three viruses. The protective threshold against the CJN and TC2009-1 viruses could only be achieved when the GMT against Nakayama virus was ≥ 1:20 or ≥ 1:80, respectively. Using undiluted vaccinees' sera, the enhancement of JEV infection in K562 cells was observed in some low or non-neutralizing serum specimens. CONCLUSIONS/SIGNIFICANCE: Our preliminary study has shown that neutralizing antibodies, elicited by the mouse brain-derived and formalin-inactivated JEV Nakayama vaccine among a limited number of vaccinees, have reduced neutralizing capacity against circulating GI virus, but more detailed studies are needed to address the potential impact on the future vaccine policy.

  19. A highly pathogenic porcine reproductive and respiratory syndrome virus candidate vaccine based on Japanese encephalitis virus replicon system.

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    Hu, Pingsheng; Chen, Xiaoming; Huang, Lihong; Liu, Shukai; Zang, Fuyu; Xing, Jinchao; Zhang, Youyue; Liang, Jiaqi; Zhang, Guihong; Liao, Ming; Qi, Wenbao

    2017-01-01

    In the swine industry, porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease which causes heavy economic losses worldwide. Effective prevention and disease control is an important issue. In this study, we described the construction of a Japanese encephalitis virus (JEV) DNA-based replicon with a cytomegalovirus (CMV) promoter based on the genome of Japanese encephalitis live vaccine virus SA14-14-2, which is capable of offering a potentially novel way to develop and produce vaccines against a major pathogen of global health. This JEV DNA-based replicon contains a large deletion in the structural genes (C-prM-E). A PRRSV GP5/M was inserted into the deletion position of JEV DNA-based replicons to develop a chimeric replicon vaccine candidate for PRRSV. The results showed that BALB/c mice models with the replicon vaccines pJEV-REP-G-2A-M-IRES and pJEV-REP-G-2A-M stimulated antibody responses and induced a cellular immune response. Analysis of ELSA data showed that vaccination with the replicon vaccine expressing GP5/M induced a better antibodies response than traditional DNA vaccines. Therefore, the results suggested that this ectopic expression system based on JEV DNA-based replicons may represent a useful molecular platform for various biological applications, and the JEV DNA-based replicons expressing GP5/M can be further developed into a novel, safe vaccine candidate for PRRS.

  20. Mesenchymal stem cells alleviate Japanese encephalitis virus-induced neuroinflammation and mortality.

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    Bian, Peiyu; Ye, Chuantao; Zheng, Xuyang; Yang, Jing; Ye, Wei; Wang, Yuan; Zhou, Yun; Ma, Hongwei; Han, Peijun; Zhang, Hai; Zhang, Ying; Zhang, Fanglin; Lei, Yingfeng; Jia, Zhansheng

    2017-02-16

    Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in Asia. Japanese encephalitis (JE) caused by JEV is characterized by extensive inflammatory cytokine secretion, microglia activation, blood-brain barrier (BBB) breakdown, and neuronal death, all of which contribute to the vicious cycle of inflammatory damage. There are currently no effective treatments for JE. Mesenchymal stem cells (MSCs) have been demonstrated to have a therapeutic effect on many central nervous system (CNS) diseases by regulating inflammation and other mechanisms. In vivo, 8- to 10-week-old mice were infected intraperitoneally with JEV and syngeneic bone marrow MSCs were administered through the caudal vein at 1 and 3 days post-infection. The mortality, body weight, and behavior were monitored daily. Brains from each group were harvested at the indicated times for hematoxylin and eosin staining, immunohistochemical observation, flow cytometric analysis, TUNEL staining, Western blot, quantitative real-time polymerase chain reaction, and BBB permeability assays. In vitro, co-culture and mixed culture experiments of MSCs with either microglia or neurons were performed, and then the activation state of microglia and survival rate of neurons were tested 48 h post-infection. MSC treatment reduced JEV-induced mortality and improved the recovery from JE in our mouse model. The inflammatory response, microglia activation, neuronal damage, BBB destruction, and viral load (VL) were significantly decreased in the MSC-treated group. In co-culture experiments, MSCs reprogrammed M1-to-M2 switching in microglia and improved neuron survival. Additionally, the VL was decreased in Neuro2a cells in the presence of MSCs accompanied by increased expression of interferon-α/β. MSC treatment alleviated JEV-induced inflammation and mortality in mice.

  1. Ecological Niche Modeling to Estimate the Distribution of Japanese Encephalitis Virus in Asia

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    Miller, Robin H.; Masuoka, Penny; Klein, Terry A.; Kim, Heung-Chul; Somer, Todd; Grieco, John

    2012-01-01

    Background Culex tritaeniorhynchus is the primary vector of Japanese encephalitis virus (JEV), a leading cause of encephalitis in Asia. JEV is transmitted in an enzootic cycle involving large wading birds as the reservoirs and swine as amplifying hosts. The development of a JEV vaccine reduced the number of JE cases in regions with comprehensive childhood vaccination programs, such as in Japan and the Republic of Korea. However, the lack of vaccine programs or insufficient coverage of populations in other endemic countries leaves many people susceptible to JEV. The aim of this study was to predict the distribution of Culex tritaeniorhynchus using ecological niche modeling. Methods/Principal Findings An ecological niche model was constructed using the Maxent program to map the areas with suitable environmental conditions for the Cx. tritaeniorhynchus vector. Program input consisted of environmental data (temperature, elevation, rainfall) and known locations of vector presence resulting from an extensive literature search and records from MosquitoMap. The statistically significant Maxent model of the estimated probability of Cx. tritaeniorhynchus presence showed that the mean temperatures of the wettest quarter had the greatest impact on the model. Further, the majority of human Japanese encephalitis (JE) cases were located in regions with higher estimated probability of Cx. tritaeniorhynchus presence. Conclusions/Significance Our ecological niche model of the estimated probability of Cx. tritaeniorhynchus presence provides a framework for better allocation of vector control resources, particularly in locations where JEV vaccinations are unavailable. Furthermore, this model provides estimates of vector probability that could improve vector surveillance programs and JE control efforts. PMID:22724030

  2. Acyclovir resistance in herpes simplex virus type I encephalitis: a case report.

    Science.gov (United States)

    Bergmann, M; Beer, R; Kofler, M; Helbok, R; Pfausler, B; Schmutzhard, E

    2017-04-01

    Acyclovir resistance is rarely seen in herpes simplex virus (HSV) type I encephalitis. Prevalence rates vary between 0.5 % in immunocompetent patients (Christophers et al. 1998; Fife et al. 1994) and 3.5-10 % in immunocompromised patients (Stranska et al. 2005). We report a 45-year-old, immunocompetent (negative HIV antigen/antibody testing), female patient, without previous illness who developed-after a febrile prodromal stage-aphasia and psychomotor slowing. Cerebral magnetic resonance imaging (cMRI) showed right temporal and insular T2-hyperintense lesions with spreading to the contralateral temporal lobe. Cerebrospinal fluid (CSF) analysis yielded lymphocytic pleocytosis and elevated protein level. Polymerase chain reaction testing for HSV type I showed a positive result in repeat lumbar puncture. HSV type I encephalitis was diagnosed and intravenous acyclovir treatment was initiated (750 mg t.i.d.). Acyclovir treatment was intensified to 1000 mg t.i.d., due to clinical deterioration, ongoing pleocytosis and progression on cMRI 5 days after initiation of antiviral therapy. In parallel, acyclovir resistance testing showed mutation of thymidine kinase gene at position A156V prompting foscarnet therapy (60 mg t.i.d.). Patient's condition improved dramatically over 2 weeks. Acyclovir resistance is rare but should be considered in case of clinical worsening of patient's condition. To our knowledge, this is the first report of acyclovir resistance in HSV type I encephalitis of an immunocompetent and previously healthy patient in Austria.

  3. Molecular evidence for the occurrence of Japanese encephalitis virus genotype I and III infection associated with acute Encephalitis in Patients of West Bengal, India, 2010

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    Sarkar Arindam

    2012-11-01

    Full Text Available Abstract Background Japanese encephalitis virus (JEV, a mosquito-borne zoonotic pathogen, is the sole etiologic agent of Japanese Encephalitis (JE; a neurotropic killer disease which is one of the major causes of viral encephalitis worldwide with prime public health concern. JE was first reported in the state of West Bengal, India in 1973. Since then it is being reported every year from different districts of the state, though the vaccination has already been done. Therefore, it indicates that there might be either partial coverage of the vaccine or the emergence of mutated/new strain of JEV. Considering this fact, to understand the JEV genotype distribution, we conducted a molecular epidemiological study on a total of 135 serum/cerebrospinal fluid (CSF samples referred and/or collected from the clinically suspected patients with Acute encephalitis syndrome (AES, admitted in different district hospitals of West Bengal, India, 2010. Findings JEV etiology was confirmed in 36/135 (26.6% and 13/61 (21.3% 2–15 days’ febrile illness samples from AES cases by analyzing Mac-ELISA followed by RT-PCR test respectively. Phylogenetic analysis based on complete envelope gene sequences of 13 isolates showed the emergence of JEV genotype I (GI, co-circulating with genotype III (GIII. Conclusion This study represents the first report of JEV GI with GIII, co-circulating in West Bengal. The efficacy of the vaccine (derived from JEV GIII strain SA-14-14-2 to protect against emerging JEV GI needs careful evaluation. In future, JE outbreak is quite likely in the state, if this vaccine fails to protect sufficiently against GI of JEV.

  4. IC-51, an injectable vaccine for the prevention of Japanese encephalitis virus infection.

    Science.gov (United States)

    Jones, Taff

    2009-02-01

    The mosquito-borne Japanese encephalitis (JE) virus is the major etiological agent of viral encephalitis in children living in South-East Asia, causing comas, seizures and Parkinson's disease-like movement disorders. Travelers and military personnel visiting the region are also highly susceptible to the disease. As the population in South-East Asia increases, more land is irrigated to produce rice paddies (the ideal breeding habitat for mosquitoes), and pig breeding (a zoonotic host for mosquitoes) becomes more widespread. Given the exponential growth in tourism to the region and the globalization of business and commerce, an enhanced requirement for mass vaccination exists. In the West, the current licensed vaccine against JE, JE-VAX, has been highly effective; however, the use of mouse brain-derived virus has been linked to cases of acute disseminated encephalomyelitis. Intercell AG, under license from VaccGen International LLC, is developing IC-51, a formalin-inactivated vaccine derived from cell culture-based attenuated virus that has been adapted to grow in Vero cells (African green monkey kidney cells). In extensive clinical trials performed to date, IC-51 was safe, with mild to moderate adverse events reported. In terms of immunogenicity, IC-51 was highly effective, demonstrating rapid seroconversion rates and long-term maintenance of geometric mean titers that exceeded the protective titer. The results suggests that IC-51 is fully compliant with the stringent regulatory requirements set by the WHO, has an acceptable safety profile and is non-inferior to JE-VAX.

  5. Circulation of Japanese encephalitis virus in pigs and mosquito vectors within Can Tho city, Vietnam.

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    Johanna F Lindahl

    Full Text Available Japanese encephalitis virus (JEV is a mosquito-borne, zoonotic flavivirus causing encephalitis in humans and reproductive disorder in pigs. JEV is present in large parts of Asia, where urbanization is high. Households within and outside Can Tho city, South Vietnam, were selected to monitor circulation of JEV. A nested RT-PCR was established to detect the presence of JEV in mosquitoes whereas sera from pigs belonging to households within the province were analyzed for the presence of antibodies to JEV. A total of 7885 mosquitoes were collected and divided into 352 pools whereof seven were JEV-positive, six of which were collected within the city. Fragments from four pools clustered with JEV genotype III and three with genotype I. Of the 43 pigs sampled inside the city 100% had JEV antibodies. Our study demonstrates exposure to JEV in pigs, and co-circulation of JEV genotype I and III in mosquitoes within an urban environment in South Vietnam. Thus, although JEV has mainly been considered a rural disease, the potential for transmission in urban areas cannot be ignored.

  6. miR-124 attenuates Japanese encephalitis virus replication by targeting DNM2.

    Science.gov (United States)

    Yang, Songbai; Pei, Yue; Li, Xinyun; Zhao, Shuhong; Zhu, Mengjin; Zhao, Ayong

    2016-06-21

    Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes acute viral encephalitis in humans. Pigs are important amplifier hosts of JEV. Emerging evidence indicates that host microRNAs (miRNAs) play key roles in modulating viral infection and pathogenesis. However, mechanistic studies delineating the roles of miRNAs in regulating host-JEV interactions remain scarce. In this study, we demonstrated that miR-124 inhibited JEV replication in porcine kidney epithelial PK15 cells. Furthermore, using bioinformatics tools, we identified dynamin2 (DNM2), a GTPase responsible for vesicle scission, as a target of miR-124. Small interfering RNA (siRNA) depletion studies inicated that dynamin2 was required for efficient JEV replication. We also demonstrated that upregulation of miR-124 expression corresponded to decreased expression of its target, DNM2, in the JEV-infected PK15 cells. Overall, these results suggest the importance of miR-124 in modulating JEV replication and provide a scientific basis for using cellular miRNAs in anti-JEV therapies.

  7. Circulation of Japanese Encephalitis Virus in Pigs and Mosquito Vectors within Can Tho City, Vietnam

    Science.gov (United States)

    Lindahl, Johanna F.; Ståhl, Karl; Chirico, Jan; Boqvist, Sofia; Thu, Ho Thi Viet; Magnusson, Ulf

    2013-01-01

    Japanese encephalitis virus (JEV) is a mosquito-borne, zoonotic flavivirus causing encephalitis in humans and reproductive disorder in pigs. JEV is present in large parts of Asia, where urbanization is high. Households within and outside Can Tho city, South Vietnam, were selected to monitor circulation of JEV. A nested RT-PCR was established to detect the presence of JEV in mosquitoes whereas sera from pigs belonging to households within the province were analyzed for the presence of antibodies to JEV. A total of 7885 mosquitoes were collected and divided into 352 pools whereof seven were JEV-positive, six of which were collected within the city. Fragments from four pools clustered with JEV genotype III and three with genotype I. Of the 43 pigs sampled inside the city 100% had JEV antibodies. Our study demonstrates exposure to JEV in pigs, and co-circulation of JEV genotype I and III in mosquitoes within an urban environment in South Vietnam. Thus, although JEV has mainly been considered a rural disease, the potential for transmission in urban areas cannot be ignored. PMID:23593520

  8. Genetic characterization of St. Louis encephalitis virus isolated from human in São Paulo, Brazil

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    Cecília Luiza Simões dos Santos

    2006-02-01

    Full Text Available The molecular characterization of SPH253157, a new strain of St. Louis encephalitis virus (SLEV, isolated in 2004 from the first case of human infection recognized in the state of São Paulo, Brazil, is reported. The patient, presenting a febrile illness without neurological involvement, was hospitalized as a probable case of dengue fever. Genomic RNA was isolated from the supernatant of C6/36 cells infected with acute phase-serum specimen of the patient and the envelope gene was amplified by reverse-transcription-polymerase chain reaction. The complete nucleotide sequence of the envelope gene of this isolate was directly sequenced from the amplified products and compared with other Brazilian and American SLEV strains. Phylogenetic analyses were carried out under maximum likelihood criterion with outgroups both included and excluded. Outgroups comprised four flavivirus of the Japanese encephalitis group. Phylogeny also included Bayesian analysis. The results indicated that the new SLEV isolate belongs to lineage III, being closely related to an Argentinean strain recovered from Culex sp. in 1979. It is concluded that there are at least 3 lineages of SLEV in Brazil.

  9. Construction and characterization of recombinant Japanese encephalitis virus carrying brainspecific miRNA target sequences

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    Wen-yuan CAO

    2014-08-01

    Full Text Available Objective To construct the recombinant Japanese encephalitis virus ( JEV carrying brain-specific miRNA targeting sequences. Methods The target sequences of brain-specific miR-124 and miR-125 were introduced into the infectious cDNA clone of JEV to generate recombinant plasmids based on reverse genetics technology. The recombinant plasmids were linearized with Xho Ⅰ and served as templates of transcription with SP6 RNA polymerase to generate infectious viral RNA. The RNA transcripts were then transfected into BHK-21 cells, and the supernatant was obtained after incubated at 37℃, 5% CO2 for 3 days. The cytopathic changes of BHK-21 cells inoculated with the supernatant were observed after one passage. The rescued viruses carrying miRNA target sequences were validated by RT-PCR, standard plaque forming test on BHK-21 cells and growth curves analysis. Results Two recombinant viruses carrying miR-124 or miR-125 target sequence were rescued, respectively. The insertion of miRNA target sequences was confirmed by DNA sequencing. The rescued viruses yielded similar plaque morphology and replication efficiency compared with wild type JEV. Conclusion The recombinant JEV containing brain-specific miRNA target sequences can be obtained by reverse genetics technique, which could be used in further studies of miRNA-mediated tissue-specific attenuation mechanism of JEV. DOI: 10.11855/j.issn.0577-7402.2014.06.01

  10. Mx Is Not Responsible for the Antiviral Activity of Interferon-α against Japanese Encephalitis Virus

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    Jing Zhou

    2017-01-01

    Full Text Available Mx proteins are interferon (IFN-induced dynamin-like GTPases that are present in all vertebrates and inhibit the replication of myriad viruses. However, the role Mx proteins play in IFN-mediated suppression of Japanese encephalitis virus (JEV infection is unknown. In this study, we set out to investigate the effects of Mx1 and Mx2 expression on the interferon-α (IFNα restriction of JEV replication. To evaluate whether the inhibitory activity of IFNα on JEV is dependent on Mx1 or Mx2, we knocked down Mx1 or Mx2 with siRNA in IFNα-treated PK-15 cells and BHK-21 cells, then challenged them with JEV; the production of progeny virus was assessed by plaque assay, RT-qPCR, and Western blotting. Our results demonstrated that depletion of Mx1 or Mx2 did not affect JEV restriction imposed by IFNα, although these two proteins were knocked down 66% and 79%, respectively. Accordingly, expression of exogenous Mx1 or Mx2 did not change the inhibitory activity of IFNα to JEV. In addition, even though virus-induced membranes were damaged by Brefeldin A (BFA, overexpressing porcine Mx1 or Mx2 did not inhibit JEV proliferation. We found that BFA inhibited JEV replication, not maturation, suggesting that BFA could be developed into a novel antiviral reagent. Collectively, our findings demonstrate that IFNα inhibits JEV infection by Mx-independent pathways.

  11. Molecular detection and genotyping of Japanese Encephalitis Virus in mosquitoes during a 2010 outbreak in the Republic of Korea

    Science.gov (United States)

    Seo, Hyun-Ji; Kim, Heung Chul; Klein, Terry A.; Ramey, Andrew M.; Lee, Ji-Hyee; Kyung, Soon-Goo; Park, Jee-Yong; Cho, In-Soo; Yeh, Jung-Yong

    2013-01-01

    Japanese encephalitis virus (JEV), a mosquito-borne zoonotic pathogen, is one of the major causes of viral encephalitis. To reduce the impact of Japanese encephalitis among children in the Republic of Korea (ROK), the government established a mandatory vaccination program in 1967. Through the efforts of this program only 0-7 (mean 2.1) cases of Japanese encephalitis were reported annually in the ROK during the period of 1984-2009. However, in 2010 there was an outbreak of 26 confirmed cases of Japanese encephalitis, including 7 deaths. This represented a >12-fold increase in the number of confirmed cases of Japanese encephalitis in the ROK as compared to the mean number reported over the last 26 years and a 3.7-fold increase over the highest annual number of cases during this same period (7 cases). Surveillance of adult mosquitoes was conducted during the 2010 outbreak of Japanese encephalitis in the ROK. A total of 6,328 culicine mosquitoes belonging to 12 species from 5 genera were collected at 6 survey sites from June through October 2010 and assayed by reverse-transcription polymerase chain reaction (RT-PCR) for the presence of JEV. A total of 34/371 pooled samples tested positive for JEV (29/121 Culex tritaeniorhynchus, 4/64 Cx. pipiens, and 1/26 Cx. bitaeniorhynchus) as confirmed by sequencing of the pre-membrane and envelope protein coding genes. The maximum likelihood estimates of JEV positive individuals per 1,000 culicine vectors for Cx. tritaeniorhynchus, Cx. pipiens, and Cx. bitaeniorhynchus were 11.8, 5.6, and 2.8, respectively. Sequences of the JEV pre-membrane and envelope protein coding genes amplified from the culicine mosquitoes by RT-PCR were compared with those of JEV genotypes I-V. Phylogenetic analyses support the detection of a single genotype (I) among samples collected from the ROK in 2010.

  12. Establishment of an analyzing method for a Japanese encephalitis virus neutralization test in Vero cells.

    Science.gov (United States)

    Abe, Motoharu; Kuzuhara, Syoji; Kino, Yoichiro

    2003-05-16

    We established a 50% plaque reduction analyzing method of neutralizing antibody for human serum to Japanese encephalitis virus (JEV) in Vero cells, called the '3 points least-squares regression method' (3LSRM). Our method shows a high correlation with the chick embryo cell method (the current standard method for human serum), using the chart method established by the National Institute of Infectious Diseases of Japan, which is an equation made with retrospective data obtained with the 50% plaque reduction method as a standard measurement method for neutralizing antibody titers to JEV. Our new method is much simpler and more reliable than the current method in that it uses an established cell line, Vero cells, and its results are computed by the 3LSRM.

  13. Serosurveillance of Eastern Equine Encephalitis Virus in Amphibians and Reptiles from Alabama, USA

    Science.gov (United States)

    Graham, Sean P.; Hassan, Hassan K.; Chapman, Taryn; White, Gregory; Guyer, Craig; Unnasch, Thomas R.

    2012-01-01

    Eastern equine encephalitis virus (EEEV) is among the most medically important arboviruses in North America, and studies suggest a role for amphibians and reptiles in its transmission cycle. Serum samples collected from 351 amphibians and reptiles (27 species) from Alabama, USA, were tested for the presence of antibodies against EEEV. Frogs, turtles, and lizards showed little or no seropositivity, and snakes had high seropositivity rates. Most seropositive species were preferred or abundant hosts of Culex spp. mosquitoes at Tuskegee National Forest, that target ectothermic hosts. The cottonmouth, the most abundant ectotherm sampled, displayed a high prevalence of seropositivity, indicating its possible role as an amplification and/or over-wintering reservoir for EEEV. PMID:22403333

  14. Correlation of in vivo neuroimaging abnormalities with postmortem human immunodeficiency virus encephalitis and dendritic loss

    DEFF Research Database (Denmark)

    Archibald, Sarah L.; Masliah, Eliezer; Fennema-Notestine, Christine

    2004-01-01

    previous studies have linked brain viral levels to these alterations, other neuropathological mechanisms might also contribute to them. OBJECTIVE: To examine the relationship between findings on premortem magnetic resonance images and postmortem neuropathologic evidence of human immunodeficiency virus (HIV......) encephalitis and neurodegeneration. DESIGN: Morphometric analysis of magnetic resonance imaging in seropositive cases with matched seronegative controls, and the correlation of these volumes to neuropathological measures in autopsied seropositive cases. SETTING: University of California, San Diego, HIV...... Neurobehavioral Research Center. SUBJECTS: Twenty-one seropositive subjects studied at autopsy and 19 seronegative cases. MAIN OUTCOME MEASURES: In vivo structural magnetic resonance imaging data analyzed by quantitative methods, with comparison of volumes from magnetic resonance imaging and neuropathological...

  15. Focal encephalitis following varicella-zoster virus reactivation without rash in a healthy immunized young adult.

    Science.gov (United States)

    Halling, Geoffrey; Giannini, Caterina; Britton, Jeffrey W; Lee, Ricky W; Watson, Robert E; Terrell, Christine L; Parney, Ian F; Buckingham, Erin M; Carpenter, John E; Grose, Charles

    2014-09-01

    Herein we describe an episode of focal varicella-zoster virus (VZV) encephalitis in a healthy young man with neither rash nor radicular pain. The symptoms began with headaches and seizures, after which magnetic resonance imaging detected a single hyperintense lesion in the left temporal lobe. Because of the provisional diagnosis of a brain tumor, the lesion was excised and submitted for pathological examination. No tumor was found. But the tissue immunostained positively for VZV antigens, and wild-type VZV sequences were detected. In short, this case represents VZV reactivation, most likely in the trigeminal ganglion, in the absence of clinical herpes zoster. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. A first note on Japanese encephalitis virus isolation from Culex quinquefasciatus Say in Northern West Bengal.

    Directory of Open Access Journals (Sweden)

    V. Thenmozhi

    2014-03-01

    Full Text Available Japanese encephalitis (JE is endemic in many parts of India including the state of West Bengal. In West Bengal, the first major outbreaks of JE occurred in the districts of Bankura and Burdwan in 1973. The Culex vishnui subgroup of mosquitoes has been implicated as major vectors of JE. However in India, JE virus (JEV has been isolated from 16 species of mosquitoes. During September 2011, JE cases were reported from four districts -Jalpaiguri, Darjeeling, Dinajpur and Cooch Behar of West Bengal (North. Adult mosquitoes were collected, identified, pooled and screened for JEV using antigen capture ELISA. Out of 279 mosquito pools tested, one pool of Cx. pseudovishnui and three pools of Cx. quinquefasciatus were found positive for JEV. The ELISA positive pools were further confirmed as JEV by insect bioassay (Toxo-IFA. Two pools of Cx. quinquefasciatus were confirmed as JEV. This represents the first report of JEV isolation from Cx. quinquefasciatus in West Bengal.

  17. Molecular epidemiology of Japanese encephalitis virus circulating in South Korea, 1983-2005

    Science.gov (United States)

    2010-01-01

    We sequenced the envelope (E) gene of 17 strains of the Japanese encephalitis virus (JEV) isolated in South Korea in 1983-2005 and compared the sequences with those from previously reported strains. Our results show the remarkable genetic stability of the E gene sequence in Korean JEV strains. Five pairs of E gene sequences from 10 Korean strains were identical, despite geographical differences and a maximum five-year time span. Sequence comparisons with other Asian strains revealed that the Korean strains are closely related to those from China, Japan, and Vietnam. Genotype 3 strains were predominant in Korea before 1993, when genotype 1 strain K93A07 was first isolated. The two genotypes were detected simultaneously in 1994 but since then, only genotype 1 has been isolated in South Korea. Thus, the genotype change occurred according to the year of isolation rather than the geographical origin. PMID:20546562

  18. [Generation of Japanese Encephalitis Virus-like Particle Vaccine and Preliminary Evaluation of Its Protective Efficiency].

    Science.gov (United States)

    Zhang, Yanfang; Du, Ruikun; Huang, Shaomei; Zhang, Tao; Liu, Jinliang; Zhu, Bibo; Wang, Hualin; Deng, Fei; Cao, Shengbo

    2016-03-01

    The cDNA fragment of JEV prME gene was cloned into the baculovirus shuttle vector (bacmid) to construct a recombinant baculovirus vector, defined as AcBac-prME. Then the recombinant baculovirus Ac-prME was obtained by transfecting Sf9 cells with AcBac-prME. Western blot analysis and immunofluorescence results indicated that both prM and E proteins were efficiently expressed in Sf9 cells. Electron microscopy suggested that prME was assembled into JEV-VLPs. To further evaluate the potential of JEV-VLPs as vaccine, the mice were immunized with JEV-VLPs and then challenged with lethal JEV. The results of mice survival and pathological changes demonstrated that the JEV-VLPs performed complete protection against JEV-P3 strain and relieved pathological changes in the mice brain significant. This study suggest that JEV-VLPs would be a potential vaccine for Japanese encephalitis virus.

  19. Prevalence of antibodies to Japanese encephalitis virus among pigs in Bali and East Java, Indonesia, 2008.

    Science.gov (United States)

    Yamanaka, Atsushi; Mulyatno, Kris Cahyo; Susilowati, Helen; Hendrianto, Eryk; Utsumi, Takako; Amin, Mochamad; Lusida, Maria Inge; Soegijanto, Soegeng; Konishi, Eiji

    2010-01-01

    Japanese encephalitis virus (JEV) is a fatal disease in Asia. Pigs are considered to be the effective amplifying host for JEV in the peridomestic environment. Bali Island and Java Island in Indonesia provide a model to assess the effect of pigs on JEV transmission, since the pig density is nearly 100-fold higher in Bali than Java, while the geographic and climatologic environments are equivalent in these areas. We surveyed antibodies to JEV among 123 pigs in Mengwi (Bali) and 96 pigs in Tulungagung (East Java) in 2008 by the hemagglutination-inhibition (HAI) test. Overall prevalences were 49% in Bali and 6% in Java, with a significant difference between them (P Java. In addition, 2-mercaptoethanol-sensitive antibodies were found only from Bali samples. Further, the average HAI antibody titer obtained from positive samples was significantly higher in Bali (1:52) than Java (1:10; P Java.

  20. Transient widespread cortical and splenial lesions in acute encephalitis/encephalopathy associated with primary Epstein–Barr virus infection

    Directory of Open Access Journals (Sweden)

    Shuo Zhang

    2016-01-01

    Full Text Available Infection with Epstein–Barr virus (EBV is very common and usually occurs in childhood or early adulthood. Encephalitis/encephalopathy is an uncommon but serious neurological complication of EBV. A case of EBV-associated encephalitis/encephalopathy with involvement of reversible widespread cortical and splenial lesions is presented herein. An 8-year-old Chinese girl who presented with fever and headache, followed by seizures and drowsiness, was admitted to the hospital. Magnetic resonance imaging revealed high signal intensities on diffusion-weighted imaging in widespread cortical and splenial lesions. The clinical and laboratory examination results together with the unusual radiology findings suggested acute encephalitis/encephalopathy due to primary EBV infection. After methylprednisolone pulse therapy together with ganciclovir, the patient made a full recovery without any brain lesions. The hallmark clinical–radiological features of this patient included severe encephalitis/encephalopathy at onset, the prompt and complete recovery, and rapidly reversible widespread involvement of the cortex and splenium. Patients with EBV encephalitis/encephalopathy who have multiple lesions, even with the widespread involvement of cortex and splenium of the corpus callosum, may have a favorable outcome with complete disappearance of all brain lesions.

  1. Construction and immune efficacy of recombinant pseudorabies virus expressing PrM-E proteins of Japanese encephalitis virus genotype І.

    Science.gov (United States)

    Qian, Ping; Zhi, Xianwei; Wang, Bo; Zhang, Huawei; Chen, Huanchun; Li, Xiangmin

    2015-12-10

    Japanese encephalitis (JE) is an arboviral disease with high case fatality rates and neurologic or psychiatric sequelae among survivors in Asia, western Pacific countries and northern Australia. Japanese encephalitis virus (JEV) is the cause of JE and the emergence of genotype І (GI) JEV has displaced genotype III (GIII) as the dominant strains circulating in some Asian regions. The currently available JE vaccines are safe and effective in preventing this disease, but they are developed based on the GIII JEV strains. The recombinant virus PRV TK(-)/gE(-)/PrM-E(+) which expressed the premembrane (prM) and envelope (E) proteins of JEV SX09S-01 strain (genotype I, GI) was constructed by homologous recombination between the genome of PRV TK(-)/gE(-)/LacZ(+) digested with EcoRI and plasmid pIE-CAG-PrM-E-BGH. Expression of JEV PrM and E proteins was analyzed by Western blot analysis. Immune efficacy of PRV TK(-)/gE(-)/PrM-E(+) was further evaluated in mouse model. A recombinant pseudorabies virus (PRV TK(-)/gE(-)/PrM-E(+)) was successfully constructed. Mice experiments showed that PRV TK(-)/gE(-)/PrM-E(+) could induce a high level of ELISA antibodies against PRV and JEV, as well as high titer of PRV neutralizing antibodies. After challenge with 1 × 10(7) PFU virulent JEV SX09S-01 strain, the time of death was delayed and the survival rate was improved in PRV TK(-)/gE(-)/PrM-E(+) vaccinated mice. PRV TK(-)/gE(-)/PrM-E(+) is a potential vaccine candidate against PRV and JEV GI infection in the future.

  2. Minocycline differentially modulates macrophage mediated peripheral immune response following Japanese encephalitis virus infection.

    Science.gov (United States)

    Dutta, Kallol; Mishra, Manoj Kumar; Nazmi, Arshed; Kumawat, Kanhaiya Lal; Basu, Anirban

    2010-11-01

    Japanese encephalitis virus (JEV) is a neurotropic flavivirus that is the causative agent of a major mosquito-borne encephalitis in the world. Evasion of peripheral immune system facilitates the entry of the virus into the central nervous system (CNS) where it causes extensive neuronal inflammatory damage that leads to death or severe neuropschychiatric sequel in survivors. It has been proposed that after entry into the body, the virus is carried into the CNS by peripheral immune cells that act as Trojan horses. In this study we investigate whether macrophages can be considered as such a Trojan horse. We also investigate the role of minocycline, a synthetic tetracycline, in such processes. Minocycline has been found to be broadly protective in neurological disease models featuring inflammation and cell death but there has been no report of it having any modulatory role in peripheral macrophage-mediated immune response against viral infection. Persistence of internalized virus within macrophages was visualized by immunofluorescent staining. Cytotoxicity assay revealed that there was no significant cell death after 24 h and 72 h infection with JEV. Proinflammatory cytokine levels were elevated in cells that were infected with JEV but it was abrogated following minocycline treatment. Reactive oxygen species level was also increased after JEV infection. Nitric oxide level was found to increase after 72 h post infection but remained unchanged after 24h. The cellular levels of signaling molecules such as PI3 kinase, phophoAkt and phospho p38MAP kinase were found to be altered after JEV infection and minocycline treatment. JEV infection also affected the VEGF-MMP pathway. Increased activity of MMP-9 was detected from JEV-infected macrophage culture supernatants after 72 h; minocycline treatment resulted in reduced activity. Thus it seems that minocycline dampens peripheral immune reactions by decreasing proinflammatory cytokine release from infected macrophages and the

  3. A Bayesian Belief Network for Murray Valley encephalitis virus risk assessment in Western Australia.

    Science.gov (United States)

    Ho, Soon Hoe; Speldewinde, Peter; Cook, Angus

    2016-01-28

    Murray Valley encephalitis virus (MVEV) is a clinically important virus in Australia responsible for a number of epidemics over the past century. Since there is no vaccine for MVEV, other preventive health measures to curtail its spread must be considered, including the development of predictive risk models and maps to help direct public health interventions. This article aims to support these approaches by presenting a model for assessing MVEV risk in Western Australia (WA). A Bayesian Belief Network (BBN) for assessing MVEV risk was developed and used to quantify and map disease risks in WA. The model combined various abiotic, biotic, and anthropogenic factors that might affect the risk of MVEV into a predictive framework, based on the ecology of the major mosquito vector and waterbird hosts of MVEV. It was further refined and tested using retrospective climate data from 4 years (2000, 2003, 2009, and 2011). Implementing the model across WA demonstrated that it could predict locations of human MVEV infection and sentinel animal seroconversion in the 4 years tested with some degree of accuracy. In general, risks are highest in the State's north and lower in the south. The model predicted that short-term climate change, based on the Intergovernmental Panel on Climate Change's A1B emissions scenario, would decrease MVEV risks in summer and autumn, largely due to higher temperatures decreasing vector survival. To our knowledge, this is the first model to use a BBN to quantify MVEV risks in WA. The models and maps developed here may assist public health agencies in preparing for and managing Murray Valley encephalitis in the future. In its current form, the model is knowledge-driven and based on the analysis of potential risk factors that affect the dynamics of MVEV using retrospective data. Further work and additional testing should be carried out to test its validity in future years.

  4. NK Cell Responses to Human Tick-Borne Encephalitis Virus Infection.

    Science.gov (United States)

    Blom, Kim; Braun, Monika; Pakalniene, Jolita; Lunemann, Sebastian; Enqvist, Monika; Dailidyte, Laura; Schaffer, Marie; Lindquist, Lars; Mickiene, Aukse; Michaëlsson, Jakob; Ljunggren, Hans-Gustaf; Gredmark-Russ, Sara

    2016-10-01

    Tick-borne encephalitis virus (TBEV) is a flavivirus that is transferred to humans by infected ticks. The virus causes tick-borne encephalitis, a severe infection of the CNS with a high risk for long-lasting sequelae. Currently, no treatment exists for the disease. Understanding the cellular immune response to this infection is important to gain further understanding into the pathogenesis, treatment, and prevention of the disease. NK cells are known to participate in the control of viral infections. We performed a longitudinal analysis of the human NK cell response to TBEV infection in a cohort of infected individuals from the onset of severe clinical symptoms to the convalescence phase. NK cell activation, as measured by expression of Ki67, was apparent at the time of hospitalization. By 3 wk after hospitalization, it decreased to levels seen in healthy controls. Concomitant with the increase in NK cell activation, augmented levels of IL-12, IL-15, IL-18, IFN-γ, and TNF were detected in patient plasma. This TBEV-induced NK cell activation was restricted predominantly to differentiated CD57(+)CD56(dim) NK cells. Functionally, CD56(dim) NK cells responded poorly to target cells at the time of hospitalization, but they recovered functional capacity to control levels during the convalescent phase. In contrast, the responsiveness of NK cells to cytokine stimulation remained intact throughout the disease. These findings demonstrate that NK cells respond to TBEV infection with characteristics that are distinct from those of other human viral infections and provide insights into the NK cell response to clinical TBEV infection. Copyright © 2016 by The American Association of Immunologists, Inc.

  5. Partial Characterization of Tick-Borne Encephalitis Virus Isolates from Ticks of Southern Ukraine.

    Science.gov (United States)

    Yurchenko, Oksana O; Dubina, Dmytro O; Vynograd, Nataliya O; Gonzalez, Jean-Paul

    2017-08-01

    Tick-borne encephalitis (TBE) is the most common tick-borne viral infection in Eurasia; thousands of human cases are annually reported from several European countries. Several tick species are vectors of the tick-borne encephalitis virus (TBEV), while TBE appears to be spreading from the Eurasian continent westward to Europe. Fifteen study sites were chosen from five territories of southern Ukraine, including Odessa, Mykolaiv, Kherson Oblast, the Autonomous Republic of Crimea, and Sevastopol. Tick collection was performed in spring season of three consecutive years (1988-1990) using either flagging technique or direct collection of specimens feeding on cattle. A total of 15,243 tick imagoes and nymphs were collected from nine species, including Dermacentor marginatus, D. reticulatus, Haemaphysalis parva, H. punctata, Hyalomma marginatum, Ixodes ricinus, Rhipicephalus bursa, R. rossicus, and R. sanguineus, pooled in 282 monospecific samples. Supernatant of grinded pool was used for inoculation to suckling mice for virus isolation. Eight TBEV isolates were identified from ticks among six study sites. Ticks showed a minimum infection rate from 0.11% to 0.81%. Phylogenetic analysis of the envelope (E) protein gene of seven isolates, assigned all to the European subtype (TBEV-Eu) showing a maximum identity of 97.17% to the "Pan" TBEV-Eu reference strain. Compared to 104 TBEV-Eu isolates they clustered within the same clade as the Pan reference strain and distinguished from other TBEV-Eu isolates. Amino acid sequence analysis of the South Ukrainian TBEV-Eu isolates revealed the presence of four amino acid substitutions 67 (N), 266 (R), 306 (V), and 407 (R), in the ectodomains II and III and in the stem-anchor region of the E protein gene. This study confirmed TBEV-Eu subtype distribution in the southern region of Ukraine, which eventually overlaps with TBEV-FE (Far Eastern subtype) and TBEV-Sib (Siberian subtype) domains, showing the heterogeneity of TBEV circulating in

  6. Molecular Basis of the Divergent Immunogenicity of Two Pediatric Tick-Borne Encephalitis Virus Vaccines.

    Science.gov (United States)

    Beck, Yvonne; Fritz, Richard; Orlinger, Klaus; Kiermayr, Stefan; Ilk, Reinhard; Portsmouth, Daniel; Pöllabauer, Eva-Maria; Löw-Baselli, Alexandra; Hessel, Annett; Kölch, Doris; Howard, M Keith; Barrett, P Noel; Kreil, Thomas R

    2015-12-09

    Studies evaluating the immunogenicity of two pediatric tick-borne encephalitis virus (TBEV) vaccines have reported contradictory results. These vaccines are based on two different strains of the European TBEV subtype: FSME-Immun Junior is based on the Neudörfl (Nd) strain, whereas Encepur Children is based on the Karlsruhe (K23) strain. The antibody (Ab) response induced by these two vaccines might be influenced by antigenic differences in the envelope (E) protein, which is the major target of neutralizing antibodies. We used an established hybrid virus assay platform to compare the levels of induction of neutralizing antibodies against the two vaccine virus strains in children aged 1 to 11 years who received two immunizations with FSME-Immun Junior or Encepur Children. The influence of amino acid differences between the E proteins of the Nd and K23 vaccine strains was investigated by mutational analyses and three-dimensional computer modeling. FSME-Immun Junior induced 100% seropositivity and similar neutralizing antibody titers against hybrid viruses containing the TBEV E protein of the two vaccine strains. Encepur Children induced 100% seropositivity only against the hybrid virus containing the E protein of the homologous K23 vaccine strain. Antibody responses induced by Encepur Children to the hybrid virus containing the E protein of the heterologous Nd strain were substantially and significantly (P virus. Structure-based mutational analyses of the TBEV E protein indicated that this is due to a mutation in the DI-DII hinge region of the K23 vaccine strain E protein which may have occurred during production of the vaccine seed virus and which is not present in any wild-type TBE viruses. Our data suggest that there are major differences in the abilities of two European subtype pediatric TBEV vaccines to induce antibodies capable of neutralizing heterologous TBEV strains. This is a result of a mutation in the DI-DII hinge region of the E protein of the K23

  7. Acute infection with venezuelan equine encephalitis virus replicon particles catalyzes a systemic antiviral state and protects from lethal virus challenge.

    Science.gov (United States)

    Konopka, Jennifer L; Thompson, Joseph M; Whitmore, Alan C; Webb, Drue L; Johnston, Robert E

    2009-12-01

    The host innate immune response provides a critical first line of defense against invading pathogens, inducing an antiviral state to impede the spread of infection. While numerous studies have documented antiviral responses within actively infected tissues, few have described the earliest innate response induced systemically by infection. Here, utilizing Venezuelan equine encephalitis virus (VEE) replicon particles (VRP) to limit infection to the initially infected cells in vivo, a rapid activation of the antiviral response was demonstrated not only within the murine draining lymph node, where replication was confined, but also within distal tissues. In the liver and brain, expression of interferon-stimulated genes was detected by 1 to 3 h following VRP footpad inoculation, reaching peak expression of >100-fold over that in mock-infected animals. Moreover, mice receiving a VRP footpad inoculation 6, 12, or 24 h prior to an otherwise lethal VEE footpad challenge were completely protected from death, including a drastic reduction in challenge virus titers. VRP pretreatment also provided protection from intranasal VEE challenge and extended the average survival time following intracranial challenge. Signaling through the interferon receptor was necessary for antiviral gene induction and protection from VEE challenge. However, VRP pretreatment failed to protect mice from a heterologous, lethal challenge with vesicular stomatitis virus, yet conferred protection following challenge with influenza virus. Collectively, these results document a rapid modulation of the host innate response within hours of infection, capable of rapidly alerting the entire animal to pathogen invasion and leading to protection from viral disease.

  8. [Prevalence of antibodies against Tick-Borne Encephalitis virus in dogs from Saxony, Germany].

    Science.gov (United States)

    Balling, Anneliese; Beer, Martin; Gniel, Dieter; Pfeffer, Martin

    2015-01-01

    Tick-borne encephalitis (TBE) is the most important tick-transmitted viral disease in Europe and is caused by the TBE virus (TBEV), a member of the Flaviviridae family. In Germany, the vast majority of human TBE cases occurs in the south in so-called risk areas. However, in areas with only sporadic TBE cases, the respective risk assessment is hard to achieve. We therefore intend to use the prevalence of antibodies against TBEV in dogs as an indicator to trace such TBE endemic areas. Between August 2012 and March 2014, a total of 331 blood sera were collected from dogs all over Saxony, which hadn't left the state for the past five years. For the detection of antibodies against TBE-virus a commercial ELISA was used. Ten sera with positive or borderline ELISA results were retested by serum neutralization test. All seven ELISA-positive serum samples could be verified to contain TBE-virus-specific antibodieswith SNT titres between 1:15 and more than 1:40. We therefore found 2.1% seroprevalence in our samples. We conclude, that dogs can very well be used as sentinels, especially in areas with only sporadic TBE cases, although larger sample sizes are desired.

  9. Differential Infectivities among Different Japanese Encephalitis Virus Genotypes in Culex quinquefasciatus Mosquitoes.

    Science.gov (United States)

    Huang, Yan-Jang S; Hettenbach, Susan M; Park, So Lee; Higgs, Stephen; Barrett, Alan D T; Hsu, Wei-Wen; Harbin, Julie N; Cohnstaedt, Lee W; Vanlandingham, Dana L

    2016-10-01

    During the last 20 years, the epidemiology of Japanese encephalitis virus (JEV) has changed significantly in its endemic regions due to the gradual displacement of the previously dominant genotype III (GIII) with clade b of GI (GI-b). Whilst there is only limited genetic difference distinguishing the two GI clades (GI-a and GI-b), GI-b has shown a significantly wider and more rapid dispersal pattern in several regions in Asia than the GI-a clade, which remains restricted in its geographic distribution since its emergence. Although previously published molecular epidemiological evidence has shown distinct phylodynamic patterns, characterization of the two GI clades has only been limited to in vitro studies. In this study, Culex quinquefasciatus, a known competent JEV mosquito vector species, was orally challenged with three JEV strains each representing GI-a, GI-b, and GIII, respectively. Infection and dissemination were determined based on the detection of infectious viruses in homogenized mosquitoes. Detection of JEV RNA in mosquito saliva at 14 days post infection indicated that Cx. quinquefasciatus can be a competent vector species for both GI and GIII strains. Significantly higher infection rates in mosquitoes exposed to the GI-b and GIII strains than the GI-a strain suggest infectivity in arthropod vectors may lead to the selective advantage of previously and currently dominant genotypes. It could thus play a role in enzootic transmission cycles for the maintenance of JEV if this virus were ever to be introduced into North America.

  10. North American Birds as Potential Amplifying Hosts of Japanese Encephalitis Virus

    Science.gov (United States)

    Nemeth, Nicole; Bosco-Lauth, Angela; Oesterle, Paul; Kohler, Dennis; Bowen, Richard

    2012-01-01

    Japanese encephalitis virus (JEV) is an emerging arbovirus, and inter-continental spread is an impending threat. The virus is maintained in a transmission cycle between mosquito vectors and vertebrate hosts, including birds. We detected variation in interspecies responses among North American birds to infection with strains of two different JEV genotypes (I and III). Several native North American passerine species and ring-billed gulls had the highest average peak viremia titers after inoculation with a Vietnamese (genotype I) JEV strain. Oral JEV shedding was minimal and cloacal shedding was rarely detected. The majority of birds, both viremic (72 of 74; 97.3%) and non-viremic (31 of 37; 83.8%), seroconverted by 14 days post-inoculation and West Nile virus-immune individuals had cross-protection against JEV viremia. Reservoir competence and serologic data for a variety of avian taxa are important for development of JEV surveillance and control strategies and will aid in understanding transmission ecology in the event of JEV expansion to North America. PMID:22927494

  11. Comprehensive Mapping Antigenic Epitopes of NS1 Protein of Japanese Encephalitis Virus with Monoclonal Antibodies.

    Directory of Open Access Journals (Sweden)

    Rong-Hong Hua

    Full Text Available Japanese encephalitis virus (JEV non-structural protein 1 (NS1 contributes to virus replication and elicits protective immune responses during infection. JEV NS1-specific antibody responses could be a target in the differential diagnosis of different flavivirus infections. However, the epitopes on JEV NS1 are poorly characterized. The present study describes the full mapping of linear B-cell epitopes in JEV NS1. We generated eleven NS1-specific monoclonal antibodies from mice immunized with recombinant NS1. For epitope mapping of monoclonal antibodies, a set of 51 partially-overlapping peptides covering the entire NS1 protein were expressed with a GST-tag and then screened using monoclonal antibodies. Through enzyme-linked immunosorbent assay (ELISA, five linear epitope-containing peptides were identified. By sequentially removing amino acid residues from the carboxy and amino terminal of peptides, the minimal units of the five linear epitopes were identified and confirmed using monoclonal antibodies. Five linear epitopes are located in amino acids residues (5AIDITRK(11, (72RDELNVL(78, (251KSKHNRREGY(260, (269DENGIVLD(276, and (341DETTLVRS(348. Furthermore, it was found that the epitopes are highly conserved among JEV strains through sequence alignment. Notably, none of the homologous regions on NS1 proteins from other flaviviruses reacted with the MAbs when they were tested for cross-reactivity, and all five epitope peptides were not recognized by sera against West Nile virus or Dengue virus. These novel virus-specific linear B-cell epitopes of JEV NS1 would benefit the development of new vaccines and diagnostic assays.

  12. Comparison of genotypes I and III in Japanese encephalitis virus reveals distinct differences in their genetic and host diversity.

    Science.gov (United States)

    Han, Na; Adams, James; Chen, Ping; Guo, Zhen-yang; Zhong, Xiang-fu; Fang, Wei; Li, Na; Wen, Lei; Tao, Xiao-yan; Yuan, Zhi-ming; Rayner, Simon

    2014-10-01

    Japanese encephalitis (JE) is an arthropod-borne disease associated with the majority of viral encephalitis cases in the Asia-Pacific region. The causative agent, Japanese encephalitis virus (JEV), has been phylogenetically divided into five genotypes. Recent surveillance data indicate that genotype I (GI) is gradually replacing genotype III (GIII) as the dominant genotype. To investigate the mechanism behind the genotype shift and the potential consequences in terms of vaccine efficacy, human cases, and virus dissemination, we collected (i) all full-length and partial JEV molecular sequences and (ii) associated genotype and host information comprising a data set of 873 sequences. We then examined differences between the two genotypes at the genetic and epidemiological level by investigating amino acid mutations, positive selection, and host range. We found that although GI is dominant, it has fewer sites predicted to be under positive selection, a narrower host range, and significantly fewer human isolates. For the E protein, the sites under positive selection define a haplotype set for each genotype that shows striking differences in their composition and diversity, with GIII showing significantly more variety than GI. Our results suggest that GI has displaced GIII by achieving a replication cycle that is more efficient but is also more restricted in its host range. Japanese encephalitis is an arthropod-borne disease associated with the majority of viral encephalitis cases in the Asia-Pacific region. The causative agent, Japanese encephalitis virus (JEV), has been divided into five genotypes based on sequence similarity. Recent data indicate that genotype I (GI) is gradually replacing genotype III (GIII) as the dominant genotype. Understanding the reasons behind this shift and the potential consequences in terms of vaccine efficacy, human cases, and virus dissemination is important for controlling the spread of the virus and reducing human fatalities. We

  13. Canine distemper virus-associated encephalitis in free-living lynx (Lynx canadensis) and bobcats (Lynx rufus) of eastern Canada.

    Science.gov (United States)

    Daoust, Pierre-Yves; McBurney, Scott R; Godson, Dale L; van de Bildt, Marco W G; Osterhaus, Albert D M E

    2009-07-01

    Between 1993 and 1999, encephalitis caused by morbillivirus was diagnosed by immunohistochemistry and histology in six lynx (Lynx canadensis) and one bobcat (Lynx rufus) in the eastern Canadian provinces of New Brunswick and Nova Scotia. Five of the six cases in lynx occurred within an 11-mo period in 1996-97. A second bobcat with encephalitis caused by unidentified protozoa and a nematode larva also had immunohistochemical evidence of neurologic infection by morbillivirus. The virus was identified as canine distemper virus (CDV) by reverse transcriptase polymerase chain reaction and nucleotide sequencing in four of five animals from which frozen tissue samples were available, and it was isolated in cell culture from one of them. To our knowledge, this is the first report of disease caused by CDV in free-living felids in North America.

  14. Lymphocyte-Dominant Encephalitis and Meningitis in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy.

    Science.gov (United States)

    Mangus, Lisa M; Beck, Sarah E; Queen, Suzanne E; Brill, Samuel A; Shirk, Erin N; Metcalf Pate, Kelly A; Muth, Dillon C; Adams, Robert J; Gama, Lucio; Clements, Janice E; Mankowski, Joseph L

    2018-01-01

    A retrospective neuropathologic review of 30 SIV-infected pigtailed macaques receiving combination antiretroviral therapy (cART) was conducted. Seventeen animals with lymphocyte-dominant inflammation in the brain and/or meninges that clearly was morphologically distinct from prototypic SIV encephalitis and human immunodeficiency virus encephalitis were identified. Central nervous system (CNS) infiltrates in cART-treated macaques primarily comprised CD20+ B cells and CD3+ T cells with fewer CD68+ macrophages. Inflammation was associated with low levels of SIV RNA in the brain as shown by in situ hybridization, and generally was observed in animals with episodes of cerebrospinal fluid (CSF) viral rebound or sustained plasma and CSF viremia during treatment. Although the lymphocytic CNS inflammation in these macaques shared morphologic characteristics with uncommon immune-mediated neurologic disorders reported in treated HIV patients, including CNS immune reconstitution inflammatory syndrome and neurosymptomatic CSF escape, the high prevalence of CNS lesions in macaques suggests that persistent adaptive immune responses in the CNS also may develop in neuroasymptomatic or mildly impaired HIV patients yet remain unrecognized given the lack of access to CNS tissue for histopathologic evaluation. Continued investigation into the mechanisms and outcomes of CNS inflammation in cART-treated, SIV-infected macaques will advance our understanding of the consequences of residual CNS HIV replication in patients on cART, including the possible contribution of adaptive immune responses to HIV-associated neurocognitive disorders. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. Comparison of Four Serological Tests for Detecting Antibodies to Japanese Encephalitis Virus after Vaccination in Children

    Science.gov (United States)

    Cha, Go Woon; Cho, Jung Eun; Ju, Young Ran; Hong, Young-Jin; Han, Myung Guk; Lee, Won-Ja; Choi, Eui Yul; Jeong, Young Eui

    2014-01-01

    Objectives Several different methods are currently used to detect antibodies to Japanese encephalitis virus (JEV) in serum samples or cerebrospinal fluid. These methods include the plaque reduction neutralization test (PRNT), the hemagglutination inhibition (HI) test, indirect immunofluorescence assay (IFA), and enzyme-linked immunosorbent assay (ELISA). The purpose of this study was to compare the performance of each method in detecting vaccine-induced antibodies to JEV. Methods The study included 29 children who had completed a primary immunization schedule with an inactivated vaccine against JEV derived from mouse brain (n = 15) or a live attenuated SA14-14-2 vaccine (n = 14). Serum samples were collected between 3 months and 47 months after the last immunization. The serum samples were tested by performing the PRNT, HI test, in-house IFA, and commercial ELISA. The antibody detection rates were compared between tests. Results All 29 serum samples were positive with the PRNT, showing antibody titers from 1:20 to 1:2560. The HI test showed positive rates of 86.7% (13/15) and 71.4% (10/14) in the inactivated and live attenuated vaccine groups, respectively. The results of the IFA for immunoglobulin (Ig)G were positive in 53.3% (8/15) of children in the inactivated vaccine group and 35.7% (5/14) in the live attenuated vaccine group. Neither the IFA nor ELISA detected JEV IgM antibodies in any of the 29 children. Conclusion These results show that detection rates of vaccine-induced antibodies to JEV have a wide range (0–100%) depending on the testing method as well as the time since immunization and individual differences between children. These findings are helpful in interpreting serological test results for the diagnosis of Japanese encephalitis in situations where vaccines are widely administered. PMID:25389515

  16. Susceptibility of naïve and differentiated PC12 cells to Japanese encephalitis virus infection.

    Science.gov (United States)

    Li, Jian-Ri; Wu, Chih-Cheng; Chang, Cheng-Yi; Ou, Yen-Chuan; Lin, Shih-Yi; Wang, Ya-Yu; Chen, Wen-Ying; Raung, Shue-Ling; Liao, Su-Lan; Chen, Chun-Jung

    2017-02-01

    Japanese encephalitis is a mosquito-borne disease caused by Japanese encephalitis virus (JEV) infection. Although JEV infects and replicates in cells with multiple tissue origins, neurons are the preferential cells for JEV infection. Currently, the identities of JEV cell tropism are largely unclear. To gain better insight into the underlying identities of JEV cell tropism, this study was designed to compare the JEV cell tropism with naïve or differentiated PC12 cells. Through nerve growth factor-differentiated PC12 cells, we discovered that JEV efficiently replicated in differentiated PC12 cells rather than naïve cells. Mechanistic studies revealed that viral adsorption/attachment seemed not to be a crucial factor. Supporting data showed that antagonizing postreceptor intracellular signaling of interferons, along with the activation of suppressor of cytokine signaling-3 (SOCS3) expression and protein tyrosine phosphatase activity, were apparent in differentiated PC12 cells after JEV infection. Independent of differentiating inducing agents, the upregulation of SOCS3 expression and protein tyrosine phosphatase activity, as well as preferential JEV tropism, were common in JEV-infected differentiated PC12 cells. Using cultured primary neurons, JEV efficiently replicated in embryonic neurons rather than adult neurons, and the preference was accompanied by higher SOCS3 expression and protein tyrosine phosphatase activity. Given that both SOCS3 and protein tyrosine phosphatases have been implicated in the process of neuronal differentiation, JEV infection seems to not only create an antagonizing strategy to escape host's interferon antiviral response but also takes advantage of cellular machinery to favor its replication. Taken together, current findings imply that dynamic changes within cellular regulators of antiviral machinery could be accompanied by events of neuronal differentiation, thus concurrently playing roles in the control of JEV cell tropism and

  17. SAINT LOUIS ENCEPHALITIS VIRUS IN MATO GROSSO, CENTRAL-WESTERN BRAZIL

    Directory of Open Access Journals (Sweden)

    Letícia Borges da Silva HEINEN

    2015-06-01

    Full Text Available The dengue virus (DENV, which is frequently involved in large epidemics, and the yellow fever virus (YFV, which is responsible for sporadic sylvatic outbreaks, are considered the most important flaviviruses circulating in Brazil. Because of that, laboratorial diagnosis of acute undifferentiated febrile illness during epidemic periods is frequently directed towards these viruses, which may eventually hinder the detection of other circulating flaviviruses, including the Saint Louis encephalitis virus (SLEV, which is widely dispersed across the Americas. The aim of this study was to conduct a molecular investigation of 11 flaviviruses using 604 serum samples obtained from patients during a large dengue fever outbreak in the state of Mato Grosso (MT between 2011 and 2012. Simultaneously, 3,433 female Culex spp. collected with Nasci aspirators in the city of Cuiabá, MT, in 2013, and allocated to 409 pools containing 1-10 mosquitoes, were also tested by multiplex semi-nested reverse transcription PCR for the same flaviviruses. SLEV was detected in three patients co-infected with DENV-4 from the cities of Cuiabá and Várzea Grande. One of them was a triple co-infection with DENV-1. None of them mentioned recent travel or access to sylvatic/rural regions, indicating that transmission might have occurred within the metropolitan area. Regarding mosquito samples, one pool containing one Culex quinquefasciatus female was positive for SLEV, with a minimum infection rate (MIR of 0.29 per 1000 specimens of this species. Phylogenetic analysis indicates both human and mosquito SLEV cluster, with isolates from genotype V-A obtained from animals in the Amazon region, in the state of Pará. This is the first report of SLEV molecular identification in MT.

  18. Bioinformatics for microbial genotyping of equine encephalitis viruses, orthopoxviruses, and hantaviruses.

    Science.gov (United States)

    Gardner, Shea N; Jaing, Crystal J

    2013-10-01

    Microbial genotyping is essential for forensic discrimination of pathogen strains, tracing epidemics, and understanding evolutionary processes. Phylogenetic analyses were performed and genotyping assays designed for five viral species complexes or genera: Western, Eastern, and Venezuelan equine encephalitis viruses, hantavirus segments L, M, and S, and orthopoxviruses. For each group, sequence alignments and phylogenetic trees were built. PCR signatures composed of primer pairs or TaqMan™ triplets were designed and mapped to nodes of the trees for sub-type or strain specific PCR-based identification. In addition, single nucleotide polymorphisms (SNPs) were identified and mapped to trees, and SNP microarray probes were designed to enable highly multiplexed genotyping of an unsequenced sample by hybridization. SNP-based trees corresponded well with MSA trees. Near-perfect isolate resolution was possible for all viruses analyzed computationally using either SNPs or PCR signatures. More tree nodes were represented by SNP loci than by PCR signatures, as PCR signatures often represented subsets of strains not corresponding to a branch. However, while PCR genotyping is possible, the number of PCR signatures needed to characterize an unknown can be very large. SNP microarrays are a suitable alternative, as arrays enable highly multiplexed, high resolution genotyping of an unknown in a single hybridization assay. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Achievements of an eradication program against caprine arthritis encephalitis virus in South Tyrol, Italy.

    Science.gov (United States)

    Tavella, Alexander; Bettini, Astrid; Ceol, Marco; Zambotto, Paolo; Stifter, Ernst; Kusstatscher, Natashia; Lombardi, Rosalba; Nardeli, Stefano; Beato, Maria Serena; Capello, Katia; Bertoni, Giuseppe

    2017-11-06

    Small ruminant lentivirus infections in goats affect both production and animal welfare. This represents a threat to the qualitative and quantitative growth of goat farming, recently observed in mountainous regions such as the Autonomous Province of Bolzano - South Tyrol (Italy). To monitor and eradicate the caprine arthritis encephalitis virus in this goat population, a compulsory eradication campaign was launched, based on a strict census of small ruminants and yearly serological testing of all animals, followed by the consequent culling of seropositive individuals. The campaign succeeded in completely eliminating cases of clinical disease in goats, while drastically reducing the seroprevalence at the herd as well as individual animal level. The serological outcome of the introduced control measures was determined using commercially available ELISA kits, demonstrating their suitability for use in this type of campaign, aimed at reducing seroprevalence as well as clinical manifestations of these infections. However, this clear success is diminished by the failure to achieve a complete eradication of these viruses. The reasons leading to the observed tailing phenomenon and the occurrence of new infections in already sanitised flocks are discussed and implementation of further measures are proposed. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Tick-borne encephalitis virus in dogs - is this an issue?

    Directory of Open Access Journals (Sweden)

    Dobler Gerhard

    2011-04-01

    Full Text Available Abstract The last review on Tick-borne encephalitis (TBE in dogs was published almost ten years ago. Since then, this zoonotic tick-borne arbovirus has been geographically spreading and emerging in many regions in Eurasia and continues to do so. Dogs become readily infected with TBE virus but they are accidental hosts not capable to further spread the virus. They seroconvert upon infection but they seem to be much more resistant to the clinical disease than humans. Apart from their use as sentinels in endemic areas, however, an increasing number of case reports appeared during the last decade thus mirroring the rising public health concerns. Owing to the increased mobility of people travelling to endemic areas with their companion dogs, this consequently leads to problems in recognizing and diagnosing this severe infection in a yet non-endemic area, simply because the veterinarians are not considering TBE. This situation warrants an update on the epidemiology, clinical presentation and possible preventions of TBE in the dog.

  1. Epidemiological Study of Japanese Encephalitis Virus in Vientiane, Lao PDR, in 1990s

    Science.gov (United States)

    Saito, Mika; Soukaloun, Douangdao; Phongsavath, Khampe; Phommasack, Bounlay; Makino, Yoshihiro

    2015-01-01

    Phylogenetic analysis of Japanese encephalitis virus (JEV) was conducted using core-premembrane and envelope gene sequence data of two strains from Vientiane, Lao People's Democratic Republic, in 1993 and five from Okinawa, Japan, in 2002 and 2003, and previously published strains. The two Vientiane strains designated as LaVS56 and LaVS145 belonged to genotype 1 (G1) and the same subcluster of G1 as Australian strain in 2000, Thai strains in 1982–1985 and 2004-2005, and Vietnamese strain in 2005, but were distinct from the subcluster of recently distributing G1 strains widely in Asia including Okinawan strains and recent Lao strain in 2009. These clusters with own distinct distributions indicated involvements of different mechanisms and routes of spreading viruses and clarified that Australian G1 strain is from Southeast Asia, not from East Asia. Both Vientiane strains were antigenically close to P19-Br (G1, isolate, Thailand), but distinct from Nakayama (G3, prototype strain, Japan), Beijing-1 (G3, laboratory strain, China), and JaGAr#01 (G3, laboratory strain, Japan), demonstrated by cross-neutralization tests using polyclonal antisera. These results together with seroepidemiologic study conducted in Vientiane strongly suggest that diversified JEV cocirculated there in early 1990s. PMID:25695095

  2. Infected dendritic cells are sufficient to mediate the adjuvant activity generated by Venezuelan equine encephalitis virus replicon particles

    OpenAIRE

    Tonkin, Daniel R; Whitmore, Alan; Johnston, Robert E; Barro, Mario

    2012-01-01

    Replicon particles derived from Venezuelan equine encephalitis virus (VEE) are infectious non-propagating particles which act as a safe and potent systemic, mucosal, and cellular adjuvant when delivered with antigen. VEE and VEE replicon particles (VRP) can target multiple cell types including dendritic cells (DCs). The role of these cell types in VRP adjuvant activity has not been previously evaluated, and for these studies we focused on the contribution of DCs to the response to VRP. By ana...

  3. MicroRNA transcriptome profiling of mice brains infected with Japanese encephalitis virus by RNA sequencing.

    Science.gov (United States)

    Li, Xin-Feng; Cao, Rui-Bing; Luo, Jun; Fan, Jian-Ming; Wang, Jing-Man; Zhang, Yuan-Peng; Gu, Jin-Yan; Feng, Xiu-Li; Zhou, Bin; Chen, Pu-Yan

    2016-04-01

    Japanese encephalitis (JE) is a mosquito borne viral disease, caused by Japanese encephalitis virus (JEV) infection producing severe neuroinflammation in the central nervous system (CNS) with the associated disruption of the blood brain barrier. MicroRNAs (miRNAs) are a family of 21-24 nt small non-coding RNAs that play important post-transcriptional regulatory roles in gene expression and have critical roles in virus pathogenesis. We examined the potential roles of miRNAs in JEV-infected suckling mice brains and found that JEV infection changed miRNA expression profiles when the suckling mice began showing nervous symptoms. A total of 1062 known and 71 novel miRNAs were detected in JEV-infected group, accompanied with 1088 known and 75 novel miRNAs in mock controls. Among these miRNAs, one novel and 25 known miRNAs were significantly differentially expressed, including 18 up-regulated and 8 down-regulated miRNAs which were further confirmed by real-time PCR. Gene ontology (GO) and signaling pathway analysis of the predicted target mRNAs of the modulated miRNAs showed that they are correlated with the regulation of apoptosis, neuron differentiation, antiviral immunity and infiltration of mouse brain, and the validated targets of 12 differentially expressed miRNAs were enriched for the regulation of cell programmed death, proliferation, transcription, muscle organ development, erythrocyte differentiation, gene expression, plasma membrane and protein domain specific binding. KEGG analysis further reveals that the validated target genes were involved in the Pathways in cancer, Neurotrophin signaling pathway, Toll like receptor signaling pathway, Endometrial cancer and Jak-STAT signaling pathway. We constructed the interaction networks of miRNAs and their target genes according to GO terms and KEGG pathways and the expression levels of several target genes were examined. Our data provides a valuable basis for further studies on the regulatory roles of miRNAs in JE

  4. Venezuelan equine encephalitis replicon particles can induce rapid protection against foot-and-mouth disease virus.

    Science.gov (United States)

    Diaz-San Segundo, Fayna; Dias, Camila C A; Moraes, Mauro P; Weiss, Marcelo; Perez-Martin, Eva; Owens, Gary; Custer, Max; Kamrud, Kurt; de los Santos, Teresa; Grubman, Marvin J

    2013-05-01

    We have previously shown that delivery of the porcine type I interferon gene (poIFN-α/β) with a replication-defective human adenovirus vector (adenovirus 5 [Ad5]) can sterilely protect swine challenged with foot-and-mouth disease virus (FMDV) 1 day later. However, the need of relatively high doses of Ad5 limits the applicability of such a control strategy in the livestock industry. Venezuelan equine encephalitis virus (VEE) empty replicon particles (VRPs) can induce rapid protection of mice against either homologous or, in some cases, heterologous virus challenge. As an alternative approach to induce rapid protection against FMDV, we have examined the ability of VRPs containing either the gene for green fluorescent protein (VRP-GFP) or poIFN-α (VRP-poIFN-α) to block FMDV replication in vitro and in vivo. Pretreatment of swine or bovine cell lines with either VRP significantly inhibited subsequent infection with FMDV as early as 6 h after treatment and for at least 120 h posttreatment. Furthermore, mice pretreated with either 10(7) or 10(8) infectious units of VRP-GFP and challenged with a lethal dose of FMDV 24 h later were protected from death. Protection was induced as early as 6 h after treatment and lasted for at least 48 h and correlated with induction of an antiviral response and production of IFN-α. By 6 h after treatment several genes were upregulated, and the number of genes and the level of induction increased at 24 h. Finally, we demonstrated that the chemokine IP-10, which is induced by IFN-α and VRP-GFP, is directly involved in protection against FMDV.

  5. Differential Infectivities among Different Japanese Encephalitis Virus Genotypes in Culex quinquefasciatus Mosquitoes.

    Directory of Open Access Journals (Sweden)

    Yan-Jang S Huang

    2016-10-01

    Full Text Available During the last 20 years, the epidemiology of Japanese encephalitis virus (JEV has changed significantly in its endemic regions due to the gradual displacement of the previously dominant genotype III (GIII with clade b of GI (GI-b. Whilst there is only limited genetic difference distinguishing the two GI clades (GI-a and GI-b, GI-b has shown a significantly wider and more rapid dispersal pattern in several regions in Asia than the GI-a clade, which remains restricted in its geographic distribution since its emergence. Although previously published molecular epidemiological evidence has shown distinct phylodynamic patterns, characterization of the two GI clades has only been limited to in vitro studies. In this study, Culex quinquefasciatus, a known competent JEV mosquito vector species, was orally challenged with three JEV strains each representing GI-a, GI-b, and GIII, respectively. Infection and dissemination were determined based on the detection of infectious viruses in homogenized mosquitoes. Detection of JEV RNA in mosquito saliva at 14 days post infection indicated that Cx. quinquefasciatus can be a competent vector species for both GI and GIII strains. Significantly higher infection rates in mosquitoes exposed to the GI-b and GIII strains than the GI-a strain suggest infectivity in arthropod vectors may lead to the selective advantage of previously and currently dominant genotypes. It could thus play a role in enzootic transmission cycles for the maintenance of JEV if this virus were ever to be introduced into North America.

  6. Interim Report on SNP analysis and forensic microarray probe design for South American hemorrhagic fever viruses, tick-borne encephalitis virus, henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever viruses, Rift Valley fever

    Energy Technology Data Exchange (ETDEWEB)

    Jaing, C; Gardner, S

    2012-06-05

    The goal of this project is to develop forensic genotyping assays for select agent viruses, enhancing the current capabilities for the viral bioforensics and law enforcement community. We used a multipronged approach combining bioinformatics analysis, PCR-enriched samples, microarrays and TaqMan assays to develop high resolution and cost effective genotyping methods for strain level forensic discrimination of viruses. We have leveraged substantial experience and efficiency gained through year 1 on software development, SNP discovery, TaqMan signature design and phylogenetic signature mapping to scale up the development of forensics signatures in year 2. In this report, we have summarized the whole genome wide SNP analysis and microarray probe design for forensics characterization of South American hemorrhagic fever viruses, tick-borne encephalitis viruses and henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus and Japanese encephalitis virus.

  7. Human pegivirus detected in a patient with severe encephalitis using a metagenomic pan-virus array

    DEFF Research Database (Denmark)

    Fridholm, Helena; Østergaard Sørensen, Line; Rosenstierne, Maiken W.

    2016-01-01

    We have used a metagenomic microarray to detect genomic RNA from human pegivirus in serum and cerebrospinal fluid from a patient suffering from severe encephalitis. No other pathogen was detected. HPgV in cerebrospinal fluid during encephalitis has never been reported before and its prevalence...

  8. Complete genome sequence of mumps viruses isolated from patients with parotitis, pancreatitis and encephalitis in India.

    Science.gov (United States)

    Vaidya, Sunil R; Chowdhury, Deepika T; Jadhav, Santoshkumar M; Hamde, Venkat S

    2016-04-01

    Limited information is available regarding epidemiology of mumps in India. Mumps vaccine is not included in the Universal Immunization Program of India. The complete genome sequences of Indian mumps virus (MuV) isolates are not available, hence this study was performed. Five isolates from bilateral parotitis and pancreatitis patients from Maharashtra, a MuV isolate from unilateral parotitis patient from Tamil Nadu, and a MuV isolate from encephalitis patient from Uttar Pradesh were genotyped by the standard protocol of the World Health Organization and subsequently complete genomes were sequenced. Indian MuV genomes were compared with published MuV genomes, including reference genotypes and eight vaccine strains for the genetic differences. The SH gene analysis revealed that five MuV isolates belonged to genotype C and two belonged to genotype G strains. The percent nucleotide divergence (PND) was 1.1% amongst five MuV genotype C strains and 2.2% amongst two MuV genotype G strains. A comparison with widely used mumps Jeryl Lynn vaccine strain revealed that Indian mumps isolates had 54, 54, 53, 49, 49, 38, and 49 amino acid substitutions in Chennai-2012, Kushinagar-2013, Pune-2008, Osmanabad-2012a, Osmanabad-2012b, Pune-1986 and Pune-2012, respectively. This study reports the complete genome sequences of Indian MuV strains obtained in years 1986, 2008, 2012 and 2013 that may be useful for further studies in India and globally. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Eastern equine encephalitis virus: high seroprevalence in horses from Southern Quebec, Canada, 2012.

    Science.gov (United States)

    Rocheleau, Jean-Philippe; Arsenault, Julie; Lindsay, L Robbin; DiBernardo, Antonia; Kulkarni, Manisha A; Côté, Nathalie; Michel, Pascal

    2013-10-01

    Eastern equine encephalitis virus (EEEV) is a highly pathogenic arbovirus that infects humans, horses, and other animals. There has been a significant increase in EEEV activity in southeastern Canada since 2008. Few data are available regarding nonlethal EEEV infections in mammals, and consequently the distribution and pathogenicity spectrum of EEEV infections in these hosts is poorly understood. This cross-sectional study focuses on the evaluation of viral activity in southern Quebec's horses by seroprevalence estimation. A total of 196 horses, 18 months and older, which had never been vaccinated against EEEV and have never traveled outside Canada, were sampled from 92 barns distributed throughout three administrative regions of southern Quebec. Blood samples were taken from each horse and titrated for EEEV antibodies by plaque reduction neutralization test (PRNT). Equine population vaccination coverage was estimated by surveying horse owners and equine practitioners. PRNT results revealed an EEEV seroprevalence up to 8.7%, with 95% confidence limits ranging from 4.4% to 13.0%. Vaccination coverage was estimated to be at least 79%. Our study reveals for the first time in Canada a measure of EEEV seroprevalence in horses. High seroprevalence in unvaccinated animals challenges the perception that EEEV is a highly lethal pathogen in horses. Monitoring high-risk vector-borne infections such as EEEV in animal populations can be an important element of a public health surveillance strategy, population risk assessment and early detection of epidemics.

  10. Heat shock protein 90β in the Vero cell membrane binds Japanese encephalitis virus.

    Science.gov (United States)

    Wang, Yuan; Li, Yan; Ding, Tianbing

    2017-08-01

    The pathogenesis of Japanese encephalitis virus (JEV) is complex and unclearly defined, and in particular, the effects of the JEV receptor (JEVR) on diverse susceptible cells are elusive. In contrast to previous studies investigating JEVR in rodent or mosquito cells, in this study, we used primate Vero cells instead. We noted that few novel proteins co‑immunoprecipitated with JEV, and discovered that one of these was heat shock protein 90β (HSP90β), which was probed by mass spectrometry with the highest score of 60.3 after questing the monkey and human protein databases. The specific HSP90β‑JEV binding was confirmed by western blot analysis under non‑reducing conditions, and this was significantly inhibited by an anti‑human HSP90β monoclonal antibody in a dose‑dependent manner, as shown by immunofluorescence assay and flow cytometry. In addition, the results of confocal laser scanning microscopic examination demonstrated that the HSP90β‑JEV binding occurred on the Vero cell surface. Finally, JEV progeny yields determined by plaque assay were also markedly decreased in siRNA‑treated Vero cells, particularly at 24 and 36 h post‑infection. Thus, our data indicate that HSP90β is a binding receptor for JEV in Vero cells.

  11. Managing aggression in global amnesia following herpes simplex virus encephalitis: The case of E.B.

    Science.gov (United States)

    Shannon, Tracy E; Griffin, Stefanie L

    2015-01-01

    This article describes an integrative approach to the case of EB, a 33 year old male who presented with agitation, delusional ideation and global amnesia after contracting herpes simplex virus encephalitis (HSVE) while in a state prison in 2004. Although several prior case studies have described outcome following acute onset of HSVE, this case presents a unique challenge for rehabilitation in several respects. First, EB's pre-morbid history is complicated; in contrast with prior HSVE case studies that have typically involved individuals with a relatively high level of pre-morbid functioning, EB presents with limited educational attainment and a prior history of several incarcerations for violent offenses. Post-injury, his presentation includes significant verbal aggression, threats of harm toward others, physical posturing and occasional physical aggression toward his caretakers. Third, EB presents with a fixed delusion that others are constantly taking advantage of him. These features are present in the context of global amnesia and relatively intact cognitive functioning in other domains. Following a brief review of prior HSVE case studies, this study reviews the outcomes of various pharmacological, cognitive, behavioural and integrative interventions designed for management of EB's aggression and agitation.

  12. Reproductive performance in sows in relation to Japanese Encephalitis Virus seropositivity in an endemic area.

    Science.gov (United States)

    Lindahl, Johanna; Boqvist, Sofia; Ståhl, Karl; Thu, Ho Thi Viet; Magnusson, Ulf

    2012-02-01

    Japanese Encephalitis Virus (JEV) is considered an important reproductive pathogen in pigs. Most studies of the reproductive impact of JEV have been conducted in areas where the disease occurs in seasonal epidemics. In this study, the associations between seropositivity for JEV, measured with an IgG ELISA, and the number of piglets born alive and stillborn were investigated in a tropical area endemic for JEV in Vietnam. Sixty percent of sows from four farms in the Mekong delta of Vietnam were seropositive to JEV and the Odds Ratio for a sow being infected was highest (6.4) in sows above 3.5 years (95% confidence interval 2.2-18.3). There was an association between increasing Optical Density (OD) values from the ELISA and the number of stillborn piglets in sows less than 1.5 years, but no effect of seropositivity could be shown when all sows were studied. OD values had an effect (p = 0.04) on the number of piglets born alive in the statistical analysis only when interacting with the effect of the breeds. An increase in mean OD value of the herd was correlated (p immunity in many gilts before their first pregnancy. This, in turn, may imply that JEV infection in pigs is of minor importance for the reproductive performance in endemic areas.

  13. Susceptibility of a North American Culex quinquefasciatus to Japanese Encephalitis Virus.

    Science.gov (United States)

    Huang, Yan-Jang S; Harbin, Julie N; Hettenbach, Susan M; Maki, Elin; Cohnstaedt, Lee W; Barrett, Alan D T; Higgs, Stephen; Vanlandingham, Dana L

    2015-11-01

    Japanese encephalitis virus (JEV) is a flavivirus that is transmitted by Culex (Cx.) tritaeniorhynchus in tropical and subtropical regions of Asia. The endemic transmission cycle involves domestic pigs and avian species that serve as amplification hosts; humans are incidental hosts that cannot develop a high-titer viremia sufficient for mosquito infection. Although vaccination can be an effective strategy for disease prevention and is used extensively in multiple Asian countries, unvaccinated immunologically naïve human populations can suffer from severe neurological sequelae. The potential introduction of JEV into North America would be a major threat to human and animal health. In this study, field-collected Cx. quinquefasciatus from Valdosta, Georgia, were tested for their susceptibility to JEV and their potential to develop a disseminated infection via per os infection. These results demonstrate that North American Cx. quinquefasciatus are susceptible to JEV infection and subsequent dissemination at 14 days post infection (d.p.i.). Detection of viral RNA in saliva from infected mosquitoes also indicates competent vectors for JEV can be found in North America.

  14. [Study on Spatial Dispersal and Migration Events of Japanese Encephalitis Virus].

    Science.gov (United States)

    Gao, Xiaoyan; Zhou, Haiwei; Liu, Hong; Fu, Shihong; Wang, Huanyu; Guo, Zhenyang; Li, Xiaolong; Liang, Guodong

    2015-05-01

    To explore the spatial distribution mechanism of Japanese encephalitis virus (JEV), PhyML v3.0 was used to build phylogenetic tree using JEV sequences in the dataset. PAUP v4.0 and Migrapyhla softz ware were then used to analyze the migration events. The results showed that a total of 95 migration events were observed during the dispersal of JEV throughout Asia. Further analysis revealed that Thailand, and several Chinese provinces (including Shandong, Shanghai, Sichuan and Yunnan), were the main migration sources of JEV. JEV spread from these migration sources as follows: from Thailand to Australia, Cambodia, Tibet and India; from Shanghai to eastern coastal Asian regions and Yunnan; from Shandong to Korea, Zhejiang, Hubei, Shanxi and Liaoning; from Sichuan mainly to inland regions of China, as well as Vietnam and Japan; and from Yunnan to Zhejiang. This study indicated that frequent migration events occurred during the dispersal of JEV in the Asia and Pacific regions, and that Thailand, Shandong, Shanghai, Sichuan and Yunnan were the sources of JEV dispersal.

  15. In vitro growth, pathogenicity and serological characteristics of the Japanese encephalitis virus genotype V Muar strain.

    Science.gov (United States)

    Tajima, Shigeru; Yagasaki, Kazumi; Kotaki, Akira; Tomikawa, Takumi; Nakayama, Eri; Moi, Meng Ling; Lim, Chang-Kweng; Saijo, Masayuki; Kurane, Ichiro; Takasaki, Tomohiko

    2015-09-01

    The characteristics of genotype V Japanese encephalitis virus (GV JEV) remain poorly understood as only two strains have been isolated to date. In this study, we examined the effects of the GV JEV Muar strain on in vitro growth and pathogenicity in mice; we also evaluated the efficacy of inactivated JEV vaccines against the Muar strain. Although growth of the Muar strain in mouse neuroblastoma N18 cells was clearly worse than that of the GIII Beijing-1 and GI Mie/41/2002 strains, neuroinvasiveness of the Muar strain was similar to that of the Beijing-1 strain and significantly higher than that of the Mie/41/2002 strain. The results of a plaque reduction neutralization test suggested that the neutralization ability of the JEV vaccines against the Muar strain was reduced compared with the GI and GIII strains. However, the protection potency of the JEV vaccine against the Muar strain was similar to that for the Beijing-1 strain in mice. Our data indicate that GV JEV has unique growth, virulence and antigenicity features.

  16. Induction of neutralizing antibodies to Hendra and Nipah glycoproteins using a Venezuelan equine encephalitis virus in vivo expression system.

    Science.gov (United States)

    Defang, Gabriel N; Khetawat, Dimple; Broder, Christopher C; Quinnan, Gerald V

    2010-12-16

    The emergence of Hendra Virus (HeV) and Nipah Virus (NiV) which can cause fatal infections in both animals and humans has triggered a search for an effective vaccine. Here, we have explored the potential for generating an effective humoral immune response to these zoonotic pathogens using an alphavirus-based vaccine platform. Groups of mice were immunized with Venezuelan equine encephalitis virus replicon particles (VRPs) encoding the attachment or fusion glycoproteins of either HeV or NiV. We demonstrate the induction of highly potent cross-reactive neutralizing antibodies to both viruses using this approach. Preliminary study suggested early enhancement in the antibody response with use of a modified version of VRP. Overall, these data suggest that the use of an alphavirus-derived vaccine platform might serve as a viable approach for the development of an effective vaccine against the henipaviruses. Published by Elsevier Ltd.

  17. [L-Lysine-α-Oxidase in vitro Activity in Experiments on Models of Viruses Sindbis, Forest-Spring Encephalitis, Western Nile, Tyaginya and Dhori].

    Science.gov (United States)

    Smirnova, I P; Larichev, V F; Shneider, Yu A

    2015-01-01

    The antitumor effect of L-lysine-α-oxidase from the culture fluid of Trichoderma harzianum Rifai F-180 was investigated for the first time. The in vitro studies revealed its high activity on a model of the forest-spring encephalitis virus and no activity against the Sindbis, Western Nile, Tyaginya and Dhori viruses.

  18. Long-term follow-up of Japanese encephalitis chimeric virus vaccine: Immune responses in children.

    Science.gov (United States)

    Chokephaibulkit, Kulkanya; Sirivichayakul, Chukiat; Thisyakorn, Usa; Pancharoen, Chitsanu; Boaz, Mark; Bouckenooghe, Alain; Feroldi, Emmanuel

    2016-11-04

    A single dose of live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) was shown to be immunogenic and well tolerated when given either as a booster to formalin-inactivated Japanese encephalitis (JE)-vaccine (mouse brain-derived vaccine [MBDV])-primed 2-5-year-olds, or as a primary vaccination to JE-vaccine-naïve 12-24-month-old toddlers in Thailand. A 5-year follow-up assessment of immune response persistence over time was conducted. Four additional visits (at 2, 3, 4, and 5years) for immunologic assessments were added to the original 12-month open-label crossover study, in which 100 healthy children aged 2-5years with a history of two-dose primary vaccination with MBDV (according to the Thai Expanded Program for Immunization schedule), and 200 healthy JE-vaccine-naïve 12-24-month-old toddlers, were randomized 1:1 to receive JE-CV, containing ⩾4 log 10 plaque forming units, 1month before or after hepatitis A control vaccine. In MBDV-primed 2-5-year-olds (n=78), the immune response to the JE-CV vaccine persisted up to at least 5years after vaccination with a single dose of JE-CV, with all (n=78) children seroprotected at the year 5 visit (geometric mean titers [GMT]: 2521/dil). There was no decrease of seroprotection rate over time (100% at 6months post-vaccination and 96.8% (90.3-98.9) at 5yearspost-vaccination). In JE-vaccine-naïve toddlers, a protective immune response persisted up to at least 5years in 58.8% (50.9-66.4) after a single-dose administration of JE-CV (GMT 26.71/dil; sensitivity analysis). A single-dose of JE-CV as a booster following MBDV administration provided long-lasting immunity. In JE-vaccine-naïve toddlers, despite relatively high seroprotection rates persisting over time, a subsequent booster dose is recommended following a JE-CV primary vaccination for long-term protection. This study was registered on www.clinicaltrials.gov (NCT00621764). Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Structure and Immunogenicity of Alternative Forms of the Simian Immunodeficiency Virus Gag Protein Expressed Using Venezuelan Equine Encephalitis Virus Replicon Particles

    OpenAIRE

    Cecil, Chad; West, Ande; Collier, Martha; Jurgens, Christy; Madden, Victoria; Whitmore, Alan; Johnston, Robert; Moore, Dominic T.; Swanstrom, Ronald; Davis, Nancy L.

    2007-01-01

    Venezuelan equine encephalitis virus replicon particles (VRP) were engineered to express different forms of SIV Gag to compare expression in vitro, formation of intra- and extracellular structures and induction of humoral and cellular immunity in mice. The three forms examined were full-length myristylated SIV Gag (Gagmyr+), full-length Gag lacking the myristylation signal (Gagmyr-), or a truncated form of Gagmyr- comprising only the matrix and capsid domains (MA/CA). Comparison of VRP-infect...

  20. BK Virus Encephalitis in HIV-Infected Patients: Case Report and Review

    Directory of Open Access Journals (Sweden)

    Luciana Antoniolli

    2017-01-01

    Full Text Available Encephalitis and meningitis due to BKPyV are unusual and emerging condition. Only a few cases of BKPyV encephalitis have been reported in hematopoietic stem cell transplant recipients, with the majority of cases presenting with concurrent hemorrhagic cystitis and HIV-infected patients. The authors report two HIV-infected patients with the diagnosis of BKPyV encephalitis and discuss the main clinical, diagnostic, and therapeutic aspects of this infection in patients with AIDS. Physicians should be aware to recognize the main clinical features and diagnose BKPyV central nervous infection in the setting of AIDS.

  1. Survey for hantaviruses, tick-borne encephalitis virus, and Rickettsia spp. in small rodents in Croatia.

    Science.gov (United States)

    Svoboda, Petra; Dobler, Gerhard; Markotić, Alemka; Kurolt, Ivan-Christian; Speck, Stephanie; Habuš, Josipa; Vucelja, Marko; Krajinović, Lidija Cvetko; Tadin, Ante; Margaletić, Josip; Essbauer, Sandra

    2014-07-01

    In Croatia, several rodent- and vector-borne agents are endemic and of medical importance. In this study, we investigated hantaviruses and, for the first time, tick-borne encephalitis virus (TBEV) and Rickettsia spp. in small wild rodents from two different sites (mountainous and lowland region) in Croatia. In total, 194 transudate and tissue samples from 170 rodents (A. flavicollis, n=115; A. agrarius, n=2; Myodes glareolus, n=53) were tested for antibodies by indirect immunofluorescence assays (IIFT) and for nucleic acids by conventional (hantaviruses) and real-time RT-/PCRs (TBEV and Rickettsia spp.). A total of 25.5% (24/94) of the rodents from the mountainous area revealed specific antibodies against hantaviruses. In all, 21.3% (20/94) of the samples from the mountainous area and 29.0% (9/31) from the lowland area yielded positive results for either Puumala virus (PUUV) or Dobrava-Belgrade virus (DOBV) using a conventional RT-PCR. All processed samples (n=194) were negative for TBEV by IIFT or real-time RT-PCR. Serological evidence of rickettsial infection was detected in 4.3% (4/94) rodents from the mountainous region. Another 3.2% (3/94) rodents were positive for Rickettsia spp. by real-time PCR. None of the rodents (n=76) from the lowland area were positive for Rickettsia spp. by real-time PCR. Dual infection of PUUV and Rickettsia spp. was found in one M. glareolus from the mountainous area by RT-PCR and real-time PCR, respectively. To our knowledge, this is the first detection of Rickettsia spp. in small rodents from Croatia. Phylogenetic analyses of S- and M-segment sequences obtained from the two study sites revealed well-supported subgroups in Croatian PUUV and DOBV. Although somewhat limited, our data showed occurrence and prevalence of PUUV, DOBV, and rickettsiae in Croatia. Further studies are warranted to confirm these data and to determine the Rickettsia species present in rodents in these areas.

  2. Engineering of Chimeric Protein Based on E Protein Domain III of Tick-Borne Encephalitis Virus and OmpF Porin of Yersinia pseudotuberculosis.

    Science.gov (United States)

    Stenkova, Anna M; Chopenko, Natalia S; Davydova, Ludmila A; Mazeika, Andrey N; Bystritskaya, Evgeniya P; Portnyagina, Olga Y; Anastyuk, Stanislav D; Kulbatskii, Dmitrii S; Lyukmanova, Ekaterina N; Dolgikh, Dmitriy A; Kostetsky, Eduard Y; Sanina, Nina M

    2017-07-24

    Tick-borne encephalitis poses a serious public health threat in the endemic regions. The disease treatment is restricted to symptomatic therapy, so great expectations are in the development of the prophylactic and therapeutic vaccines. The domain III of E protein of the tick-borne encephalitis virus is the main antigenic domain which includes virus-specific epitopes recognized by neutralizing antibodies. We have expressed, isolated and characterized the chimeric protein based on the fusion of domain III of E protein of the tick-borne encephalitis virus and bacterial porin OmpF from Yersinia pseudotuberculosis. The bacterial partner protein was used for decreasing toxicity and increasing immunogenicity of antigen. The chimeric protein was successfully expressed by the E. coli cells and purified using IMAC methodology. The purified protein was recognized with immunoblots by anti-E protein of tick-borne encephalitis virus monoclonal antibodies. Furthermore, the protein was able to elicit antibody response against domain III of E protein in immunized mice. The newly obtained chimeric antigen could be valuable for the development of the preventing tick-borne encephalitis subunit vaccines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Humoral, mucosal, and cellular immunity in response to a human immunodeficiency virus type 1 immunogen expressed by a Venezuelan equine encephalitis virus vaccine vector.

    OpenAIRE

    Caley, I J; Betts, M R; Irlbeck, D M; Davis, N L; Swanstrom, R; Frelinger, J A; Johnston, R E

    1997-01-01

    A molecularly cloned attenuated strain of Venezuelan equine encephalitis virus (VEE) has been genetically configured as a replication-competent vaccine vector for the expression of heterologous viral proteins (N. L. Davis, K. W. Brown, and R. E. Johnston, J. Virol. 70:3781-3787, 1996). The matrix/capsid (MA/CA) coding domain of human immunodeficiency virus type 1 (HIV-1) was cloned into the VEE vector to determine the ability of a VEE vector to stimulate an anti-HIV immune response in mice. T...

  4. Zika virus-induced neurological critical illness in Latin America: Severe Guillain-Barre Syndrome and encephalitis.

    Science.gov (United States)

    Sebastián, Ugarte Ubiergo; Ricardo, Arenas Villamizar Angel; Alvarez, Bruno C; Cubides, Angela; Luna, Angélica F; Arroyo-Parejo, Max; Acuña, Cayri E; Quintero, Agamenón V; Villareal, Orlando Ch; Pinillos, Oscar S; Vieda, Elías; Bello, Manuel; Peña, Susana; Dueñas-Castell, Carmelo; Rodriguez, Gloria M V; Ranero, Jorge L M; López, Rosa L M; Olaya, Sandra G; Vergara, José C; Tandazo, Ana; Ospina, Juan P S; Leyton Soto, Igor M; Fowler, R A; Marshall, John C

    2017-08-09

    Zika virus (ZIKAV) is classically described as causing minor symptoms in adult patients, however neurologic complications have been recognized. The recent outbreak in Central and South America has resulted in serious illness in some adult patients. We report adult patients in Latin America diagnosed with ZIKAV infection admitted to Intensive Care Units (ICUs). Multicenter, prospective case series of adult patients with laboratory diagnosis of ZIKAV in 16 ICUs in 8 countries. Between December 1st 2015 and April 2nd 2016, 16 ICUs in 8 countries enrolled 49 critically ill patients with diagnosis of ZIKAV infection. We included 10 critically ill patients with ZIKAV infection, as diagnosed with RT-PCR, admitted to the ICU. Neurologic manifestations concordant with Guillain-Barre Syndrome (GBS) were present in all patients, although 2 evolved into an encephalitis-like picture. 2 cases died, one due to encephalitis, the other septic shock. Differing from what was usually reported, ZIKAV infection can result in life-threatening neurologic illness in adults, including GBS and encephalitis. Collaborative reporting to identify severe illness from an emerging pathogen can provide valuable insights into disease epidemiology and clinical presentation, and inform public health authorities about acute care priorities. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Investigation of the genotype III to genotype I shift in Japanese encephalitis virus and the impact on human cases.

    Science.gov (United States)

    Han, Na; Adams, James; Fang, Wei; Liu, Si-Qing; Rayner, Simon

    2015-08-01

    Japanese encephalitis is a mosquito borne disease and is the leading cause of viral encephalitis in the Asia-Pacific area. The causative agent, Japanese encephalitis virus (JEV) can be phylogenetically classified into five genotypes based on nucleotide sequence. In recent years, genotype I (GI) has displaced genotype III (GIII) as the dominant lineage, but the mechanisms behind this displacement event requires elucidation. In an earlier study, we compared host variation over time between the two genotypes and observed that GI appears to have evolved to achieve more efficient infection in hosts in the replication cycle, with the tradeoff of reduced infectivity in secondary hosts such as humans. To further investigate this phenomenon, we collected JEV surveillance data on human cases and, together with sequence data, and generated genotype/case profiles from seven Asia-Pacific countries and regions to characterize the GI/GIII displacement event. We found that, when comprehensive and consistent vaccination and surveillance data was available, and the GIII to GI shift occurred within a well-defined time period, there was a statistically significant drop in JEV human cases. Our findings provide further support for the argument that GI is less effective in infecting humans, who represent a dead end host. However, experimental investigation is necessary to confirm this hypothesis. The study highlights the value of alternative approaches to investigation of epidemics, as well as the importance of effective data collection for disease surveillance and control.

  6. A long term study of goats naturally infected with caprine arthritis-encephalitis virus.

    Science.gov (United States)

    Hanson, J; Hydbring, E; Olsson, K

    1996-01-01

    The caprine arthritis-encephalitis virus (CAEV) is a big problem in dairy goat industry. Little is known about its characteristics in naturally infected goat herds. The aims of this study were: 1) to study how antibody expression, measured by agar gel immunodiffusion test (AGIDT), varied over time in naturally infected, seropositive goats, 2) to observe clinical signs in seropositive adult goats and 3) to follow seroconversion and gamma globulin concentration in goat kids artificially reared on cow milk replacement product only, compared to kids reared on untreated goat milk. The antibody expression pattern to the viral proteins gp135 and p28 varied in the individual goat and intermittent negative reactions were seen in 19 adult animals followed for 30-91 weeks. Four seropositive goats developed clinical symptoms with difficulties to move. However, no correlation between clinical signs and antibody expression pattern was seen. During the first 27 weeks of age no kid in the milk replacement reared group (N = 4) seroconverted, but 5 of the 7 kids fed goat milk occasionally showed a positive antibody reaction. The gamma globulin concentration was significantly higher in the goat milk fed group until the kids had become more than 19 weeks old. The results show that a great variation of the antibody pattern in individual goats occurs, and therefore the AGIDT is only reliable as a herd screening test. Frequent sampling is necessary to get reliable information about spreading of the CAEV in a naturally infected goat herd. Removing kids from their dams immediately after birth combined with segregation and artificial rearing protected them from CAEV infection. However their gamma globulin concentration was initially low.

  7. Diagnosis of Caprine Arthritis Encephalitis Virus infection in dairy goats by ELISA, PCR and Viral Culture.

    Science.gov (United States)

    Panneum, S; Rukkwamsuk, T

    2017-03-01

    For preventive and control strategies of Caprine Arthritis Encephalitis Virus (CAEV) infection in dairy goats, performance of the available diagnostic tests was described as one of the most important and necessary aspects. The study aimed at evaluating the diagnostic test performance, including PCR, ELISA and viral culture, for CAEV infection in dairy goats in Thailand. Blood samples of 29 dairy goats from five low- to medium-prevalence herds and one very low-prevalence herd were collected for PCR and ELISA methods. The performance of these two diagnostic methods was evaluated by comparing with cytopathic effects (CPE) in the co-cultivation of CAEV and primary synovial cells. Results indicated that sensitivity, specificity were, respectively, 69.6%, 100%, for PCR; and 95.7%, 83.3% for ELISA. The PCR assay tended to have lower sensitivity and higher specificity than ELISA. When multiple tests were applied, parallel testing provided sensitivity and specificity of 98.7% and 83.3%, while series testing showed sensitivity and specificity of 66.6% and 100% respectively. These results indicated that combination of ELISA and PCR provided some advantages and possibly offered optimal methods to detect CAEV-infected goats. Kappa value of the agreement between PCR and ELISA test was 0.34, indicating fair agreement. Regarding the possibility of antigenic variation between CAEV strains used in both PCR and ELISA assays, the actual circulating CAEV strain should be reviewed in order to develop and enhance the diagnostic tests using the CAE viral antigens derived from specific local strains of Thailand.

  8. Fatal Caprine arthritis encephalitis virus-like infection in 4 Rocky Mountain goats (Oreamnos americanus).

    Science.gov (United States)

    Patton, Kristin M; Bildfell, Robert J; Anderson, Mark L; Cebra, Christopher K; Valentine, Beth A

    2012-03-01

    Over a 3.5-year period, 4 Rocky Mountain goats (Oreamnos americanus), housed at a single facility, developed clinical disease attributed to infection by Caprine arthritis encephalitis virus (CAEV). Ages ranged from 1 to 10 years. Three of the goats, a 1-year-old female, a 2-year-old male, and a 5-year-old male, had been fed raw domestic goat milk from a single source that was later found to have CAEV on the premises. The fourth animal, a 10-year-old male, had not ingested domestic goat milk but had been housed with the other 3 Rocky Mountain goats. All 4 animals had clinical signs of pneumonia prior to death. At necropsy, findings in lungs included marked diffuse interstitial pneumonia characterized histologically by severe lymphoplasmacytic infiltrates with massive alveolar proteinosis, interstitial fibrosis, and type II pneumocyte hyperplasia. One animal also developed left-sided hemiparesis, and locally extensive lymphoplasmacytic myeloencephalitis was present in the cranial cervical spinal cord. Two animals had joint effusions, as well as severe lymphoplasmacytic and ulcerative synovitis. Immunohistochemical staining of fixed sections of lung tissue from all 4 goats, as well as spinal cord in 1 affected animal, and synovium from 2 affected animals were positive for CAEV antigen. Serology testing for anti-CAEV antibodies was positive in the 2 goats tested. The cases suggest that Rocky Mountain goats are susceptible to naturally occurring CAEV infection, that CAEV from domestic goats can be transmitted to this species through infected milk and by horizontal transmission, and that viral infection can result in clinically severe multisystemic disease.

  9. Prevalence of antibodies against tick-borne encephalitis virus in wild game from Saxony, Germany.

    Science.gov (United States)

    Balling, Anneliese; Plessow, Uta; Beer, Martin; Pfeffer, Martin

    2014-10-01

    Tick-borne encephalitis (TBE) is the most important tick-transmitted viral disease in Europe and is caused by the flavivirus TBE-virus (TBEV). In Germany TBE is unevenly distributed with the vast majority of cases occurring in the south in so-called risk areas defined as regions with an incidence of at least 1 case in 100,000 inhabitants. However, in low endemic areas with lesser TBE cases the respective risk assessment is hard to achieve. We therefore intend to use the prevalence of antibodies against TBEV in wildlife to trace TBEV endemic areas as a surrogate marker for the notification of human cases. This study was conducted in Saxony, Germany, where 34 autochthonous cases were reported since 2001, thereby not allowing a geographic allocation within the state. A total of 1,851 sera from wild boar and 35 sera from roe deer from all Saxon districts shot between April 2011 and March 2013 were screened for the presence of antibodies against TBEV. The overall seropositivity for Saxony was 10.5%. Among the wild boar sera, most positive samples could be found in the districts Meißen (23%) and Vogtlandkreis (20%) followed by Dresden (18%), Erzgebirgskreis and Görlitz (both 10%). We conclude that seroprevalence studies in game animals represent a promising surrogate marker and should be considered for future determination of risk areas. Although we are currently unable to explain the discrepancy of the few human cases and the high seroprevalence in some districts, vaccination against TBE should be considered for people planning outdoor activities in Dresden, Meißen or Vogtlandkreis. Copyright © 2014 Elsevier GmbH. All rights reserved.

  10. A novel immunochromatographic test applied to a serological survey of Japanese encephalitis virus on pig farms in Korea.

    Directory of Open Access Journals (Sweden)

    Go-Woon Cha

    Full Text Available Among vertebrate species, pigs are a major amplifying host of Japanese encephalitis virus (JEV and measuring their seroconversion is a reliable indicator of virus activity. Traditionally, the hemagglutination inhibition test has been used for serological testing in pigs; however, it has several limitations and, thus, a more efficient and reliable replacement test is required. In this study, we developed a new immunochromatographic test for detecting antibodies to JEV in pig serum within 15 min. Specifically, the domain III region of the JEV envelope protein was successfully expressed in soluble form and used for developing the immunochromatographic test. The test was then applied to the surveillance of Japanese encephalitis (JE in Korea. We found that our immunochromatographic test had good sensitivity (84.8% and specificity (97.7% when compared with an immunofluorescence assay used as a reference test. During the surveillance of JE in Korea in 2012, the new immunochromatographic test was used to test the sera of 1,926 slaughtered pigs from eight provinces, and 228 pigs (11.8% were found to be JEV-positive. Based on these results, we also produced an activity map of JEV, which marked the locations of pig farms in Korea that tested positive for the virus. Thus, the immunochromatographic test reported here provides a convenient and effective tool for real-time monitoring of JEV activity in pigs.

  11. The first outbreak of eastern equine encephalitis in Vermont: outbreak description and phylogenetic relationships of the virus isolate.

    Directory of Open Access Journals (Sweden)

    Kali D Saxton-Shaw

    Full Text Available The first known outbreak of eastern equine encephalitis (EEE in Vermont occurred on an emu farm in Rutland County in 2011. The first isolation of EEE virus (EEEV in Vermont (VT11 was during this outbreak. Phylogenetic analysis revealed that VT11 was most closely related to FL01, a strain from Florida isolated in 2001, which is both geographically and temporally distinct from VT11. EEEV RNA was not detected in any of the 3,905 mosquito specimens tested, and the specific vectors associated with this outbreak are undetermined.

  12. Molecular detection and phylogenetic analysis of tick-borne encephalitis virus in rodents captured in the transdanubian region of Hungary.

    Science.gov (United States)

    Pintér, Réka; Madai, Mónika; Horváth, Győző; Németh, Viktória; Oldal, Miklós; Kemenesi, Gábor; Dallos, Bianka; Bányai, Krisztián; Jakab, Ferenc

    2014-08-01

    Abstract Tick-borne encephalitis virus (TBEV) infection is a common zoonotic disease affecting humans in Europe and Asia. To determine whether TBEV is present in small mammalian hosts in Hungary, liver samples of wild rodents were tested for TBEV RNA. Over a period of 7 years, a total of 405 rodents were collected at five different geographic locations of the Transdanubian region. TBEV nucleic acid was identified in four rodent species: Apodemus agrarius, A. flavicollis, Microtus arvalis, and Myodes glareolus. Out of the 405 collected rodents, 17 small mammals (4.2%) were positive for TBEV. The present study provides molecular evidence and sequence data of TBEV from rodents in Hungary.

  13. Viral Infection of the Central Nervous System and Neuroinflammation Precede Blood-Brain Barrier Disruption during Japanese Encephalitis Virus Infection.

    Science.gov (United States)

    Li, Fang; Wang, Yueyun; Yu, Lan; Cao, Shengbo; Wang, Ke; Yuan, Jiaolong; Wang, Chong; Wang, Kunlun; Cui, Min; Fu, Zhen F

    2015-05-01

    Japanese encephalitis is an acute zoonotic, mosquito-borne disease caused by Japanese encephalitis virus (JEV). Japanese encephalitis is characterized by extensive inflammation in the central nervous system (CNS) and disruption of the blood-brain barrier (BBB). However, the pathogenic mechanisms contributing to the BBB disruption are not known. Here, using a mouse model of intravenous JEV infection, we show that virus titers increased exponentially in the brain from 2 to 5 days postinfection. This was accompanied by an early, dramatic increase in the level of inflammatory cytokines and chemokines in the brain. Enhancement of BBB permeability, however, was not observed until day 4, suggesting that viral entry and the onset of inflammation in the CNS occurred prior to BBB damage. In vitro studies revealed that direct infection with JEV could not induce changes in the permeability of brain microvascular endothelial cell monolayers. However, brain extracts derived from symptomatic JEV-infected mice, but not from mock-infected mice, induced significant permeability of the endothelial monolayer. Consistent with a role for inflammatory mediators in BBB disruption, the administration of gamma interferon-neutralizing antibody ameliorated the enhancement of BBB permeability in JEV-infected mice. Taken together, our data suggest that JEV enters the CNS, propagates in neurons, and induces the production of inflammatory cytokines and chemokines, which result in the disruption of the BBB. Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia, resulting in 70,000 cases each year, in which approximately 20 to 30% of cases are fatal, and a high proportion of patients survive with serious neurological and psychiatric sequelae. Pathologically, JEV infection causes an acute encephalopathy accompanied by BBB dysfunction; however, the mechanism is not clear. Thus, understanding the mechanisms of BBB disruption in JEV infection is important. Our data demonstrate

  14. Pathogenic and Genotypic Characterization of a Japanese Encephalitis Virus Isolate Associated with Reproductive Failure in an Indian Pig Herd.

    Science.gov (United States)

    Desingu, P A; Ray, Pradeep K; Patel, B H M; Singh, R; Singh, R K; Saikumar, G

    2016-01-01

    India is endemic to Japanese encephalitis virus (JEV) and recurrent outbreaks occur mainly in rice growing areas. Pigs are considered to be the amplifying host for JEV and infection in gestating pigs results in reproductive failure. Most studies conducted on JEV infection in Indian pigs have been serological surveys and very little is known about JEV genotypes circulating in pigs. So the potential risk posed by pigs in JEV transmission and the genetic relationship between viruses circulating in pigs, mosquitoes and humans is poorly understood. This study was conducted in pigs with a history of reproductive failure characterized by stillborn piglets with neuropathological lesions. Japanese encephalitis (JE) suspected brain specimens inoculated intracerebrally into mice and Vero cells resulted in successful isolation of JEV/SW/IVRI/395A/2014. Clinicopathological observations in infected mice, demonstration of JEV antigen in brain, and analysis of the envelope protein identified the swine isolate as being neurovirulent. Phylogenetic analysis based on prM and E gene sequences showed that it belonged to genotype III. This swine isolate was closely related to JEV associated with the 2005 outbreak in India and JaoArS982 from Japan. Phylogenetic analysis of JEV strains collected between 1956 and 2014 in India categorized the GIII viruses into different clades blurring their spatial distribution, which has been discernible in the previous century. Isolation of JEV from stillborn piglets and its close genetic relationship with viruses detected at least three decades ago in humans and mosquitoes in Japan suggests that the virus may have been circulating among Indian pigs for several decades. The close similarity between the present swine isolate and those detected in humans affected in the 2005 outbreak in Uttar Pradesh, India, suggests the need for more intensive surveillance of pigs and implementation of suitable strategies to control JE in India.

  15. Defensive Perimeter in the Central Nervous System: Predominance of Astrocytes and Astrogliosis during Recovery from Varicella-Zoster Virus Encephalitis.

    Science.gov (United States)

    Carpenter, John E; Clayton, Amy C; Halling, Kevin C; Bonthius, Daniel J; Buckingham, Erin M; Jackson, Wallen; Dotzler, Steven M; Card, J Patrick; Enquist, Lynn W; Grose, Charles

    2015-10-21

    Varicella-zoster virus (VZV) is a highly neurotropic virus that can cause infections in both the peripheral nervous system and the central nervous system. Several studies of VZV reactivation in the peripheral nervous system (herpes zoster) have been published, while exceedingly few investigations have been carried out in a human brain. Notably, there is no animal model for VZV infection of the central nervous system. In this report, we characterized the cellular environment in the temporal lobe of a human subject who recovered from focal VZV encephalitis. The approach included not only VZV DNA/RNA analyses but also a delineation of infected cell types (neurons, microglia, oligodendrocytes, and astrocytes). The average VZV genome copy number per cell was 5. Several VZV regulatory and structural gene transcripts and products were detected. When colocalization studies were performed to determine which cell types harbored the viral proteins, the majority of infected cells were astrocytes, including aggregates of astrocytes. Evidence of syncytium formation within the aggregates included the continuity of cytoplasm positive for the VZV glycoprotein H (gH) fusion-complex protein within a cellular profile with as many as 80 distinct nuclei. As with other causes of brain injury, these results suggested that astrocytes likely formed a defensive perimeter around foci of VZV infection (astrogliosis). Because of the rarity of brain samples from living humans with VZV encephalitis, we compared our VZV results with those found in a rat encephalitis model following infection with the closely related pseudorabies virus and observed similar perimeters of gliosis. Investigations of VZV-infected human brain from living immunocompetent human subjects are exceedingly rare. Therefore, much of our knowledge of VZV neuropathogenesis is gained from studies of VZV-infected brains obtained at autopsy from immunocompromised patients. These are not optimal samples with which to investigate a

  16. mosGCTL-7, a C-Type Lectin Protein, Mediates Japanese Encephalitis Virus Infection in Mosquitoes.

    Science.gov (United States)

    Liu, Ke; Qian, Yingjuan; Jung, Yong-Sam; Zhou, Bin; Cao, Ruibing; Shen, Ting; Shao, Donghua; Wei, Jianchao; Ma, Zhiyong; Chen, Puyan; Zhu, Huaimin; Qiu, Yafeng

    2017-05-15

    Japanese encephalitis virus (JEV) is an arthropod-borne flavivirus prevalent in Asia and the Western Pacific and is the leading cause of viral encephalitis. JEV is maintained in a transmission cycle between mosquitoes and vertebrate hosts, but the molecular mechanisms by which the mosquito vector participates in transmission are unclear. We investigated the expression of all C-type lectins during JEV infection in Aedes aegypti The C-type lectin mosquito galactose-specific C-type lectin 7 (mosGCTL-7) (VectorBase accession no. AAEL002524) was significantly upregulated by JEV infection and facilitated infection in vivo and in vitro mosGCTL-7 bound to the N-glycan at N154 on the JEV envelope protein. This recognition of viral N-glycan by mosGCTL-7 is required for JEV infection, and we found that this interaction was Ca(2+) dependent. After mosGCTL-7 bound to the glycan, mosPTP-1 bound to mosGCTL-7, promoting JEV entry. The viral burden in vivo and in vitro was significantly decreased by mosPTP-1 double-stranded RNA (dsRNA) treatment, and infection was abolished by anti-mosGCTL-7 antibodies. Our results indicate that the mosGCTL-7/mosPTP-1 pathway plays a key role in JEV infection in mosquitoes. An improved understanding of the mechanisms underlying flavivirus infection in mosquitoes will provide further opportunities for developing new strategies to control viral dissemination in nature.IMPORTANCE Japanese encephalitis virus is a mosquito-borne flavivirus and is the primary cause of viral encephalitis in the Asia-Pacific region. Twenty-four countries in the WHO Southeast Asia and Western Pacific regions have endemic JEV transmission, which exposes >3 billion people to the risks of infection, although JEV primarily affects children. C-type lectins are host factors that play a role in flavivirus infection in humans, swine, and other mammals. In this study, we investigated C-type lectin functions in JEV-infected Aedes aegypti and Culex pipiens pallens mosquitoes and

  17. Transcriptional Immunoprofiling at the Tick-Virus-Host Interface during Early Stages of Tick-Borne Encephalitis Virus Transmission

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    Saravanan Thangamani

    2017-12-01

    Full Text Available Emerging and re-emerging diseases transmitted by blood feeding arthropods are significant global public health problems. Ticks transmit the greatest variety of pathogenic microorganisms of any blood feeding arthropod. Infectious agents transmitted by ticks are delivered to the vertebrate host together with saliva at the bite site. Tick salivary glands produce complex cocktails of bioactive molecules that facilitate blood feeding and pathogen transmission by modulating host hemostasis, pain/itch responses, wound healing, and both innate and adaptive immunity. In this study, we utilized Illumina Next Generation Sequencing to characterize the transcriptional immunoprofile of cutaneous immune responses to Ixodes ricinus transmitted tick-borne encephalitis virus (TBEV. A comparative immune gene expression analysis of TBEV-infected and uninfected tick feeding sites was performed. Our analysis reveals that ticks create an inflammatory environment at the bite site during the first 3 h of feeding, and significant differences in host responses were observed between TBEV-infected and uninfected tick feeding. Gene-expression analysis reveals modulation of inflammatory genes after 1 and 3 h of TBEV-infected tick feeding. Transcriptional levels of genes specific to chemokines and cytokines indicated a neutrophil-dominated immune response. Immunohistochemistry of the tick feeding site revealed that mononuclear phagocytes and fibroblasts are the primary target cells for TBEV infection and did not detect TBEV antigens in neutrophils. Together, the transcriptional and immunohistochemistry results suggest that early cutaneous host responses to TBEV-infected tick feeding are more inflammatory than expected and highlight the importance of inflammatory chemokine and cytokine pathways in tick-borne flavivirus transmission.

  18. Subacute herpes simplex virus type 1 encephalitis as an initial presentation of chronic lymphocytic leukemia and multiple sclerosis: a case report

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    Corman Lourdes C

    2011-02-01

    Full Text Available Abstract Introduction Herpes simplex virus type 1 encephalitis presents acutely in patients who are immunocompetent. We report what we believe to be the first published case of a subacute course of herpes simplex virus type 1 encephalitis in a patient with asymptomatic chronic lymphocytic leukemia who subsequently developed multiple sclerosis. Case presentation A 49-year-old Caucasian woman with a history of fever blisters presented to the emergency department with a history of left temporal headache for four weeks, and numbness of the left face and leg for two weeks. A complete blood count revealed white blood cell count of 11,820 cells/mL, with an absolute lymphocyte count of 7304 cells/mL. The cerebrospinal fluid contained 6 white blood cells/μL, 63 red blood cells/μL, 54 mg glucose/dL, and 49 mg total protein/dL. Magnetic resonance imaging of the brain revealed meningoencephalitis and bilateral ventriculitis. Cerebrospinal fluid polymerase chain reaction for herpes simplex virus type 1 was positive, and the patient's symptoms resolved after ten days of treatment with parenteral aciclovir. Incidental findings on peripheral blood smear and flow cytometry testing confirmed chronic lymphocytic leukemia. One month later, she developed bilateral numbness of the hands and feet; a repeat cerebrospinal fluid polymerase chain reaction for herpes simplex virus type 1 at this time was negative. A repeat magnetic resonance imaging scan showed an expansion of the peri-ventricular lesions, and the cerebrospinal fluid contained elevated oligoclonal bands and myelin basic protein. A brain biopsy revealed gliosis consistent with multiple sclerosis, and the patient responded to treatment with high-dose parenteral steroids. Conclusion Herpes simplex virus type 1 encephalitis is a rare presentation of chronic lymphocytic leukemia. Our patient had an atypical, subacute course, presumably due to immunosuppression from chronic lymphocytic leukemia. This unusual

  19. Influence of the CCR-5/MIP-1 α Axis in the Pathogenesis of Rocio Virus Encephalitis in a Mouse Model

    Science.gov (United States)

    Chávez, Juliana H.; França, Rafael F. O.; Oliveira, Carlo J. F.; de Aquino, Maria T. P.; Farias, Kleber J. S.; Machado, Paula R. L.; de Oliveira, Thelma F. M.; Yokosawa, Jonny; Soares, Edson G.; da Silva, João S.; da Fonseca, Benedito A. L.; Figueiredo, Luiz T. M.

    2013-01-01

    Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in Brazil and its immunopathogenesis remains poorly understood. CC-chemokine receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory protein (MIP-1 α). Both molecules are associated with inflammatory cells migration during infections. In this study, we demonstrated the importance of the CCR5 and MIP-1 α, in the outcome of viral encephalitis of ROCV-infected mice. CCR5 and MIP-1 α knockout mice survived longer than wild-type (WT) ROCV-infected animals. In addition, knockout mice had reduced inflammation in the brain. Assessment of brain viral load showed mice virus detection five days post-infection in wild-type and CCR5−/− mice, while MIP-1 α−/− mice had lower viral loads seven days post-infection. Knockout mice required a higher lethal dose than wild-type mice as well. The CCR5/MIP-1 α axis may contribute to migration of infected cells to the brain and consequently affect the pathogenesis during ROCV infection. PMID:24080631

  20. Prevalence of tick-borne encephalitis virus (TBEV) RNA in Dermacentor reticulatus ticks from natural and urban environment, Poland.

    Science.gov (United States)

    Biernat, Beata; Karbowiak, Grzegorz; Werszko, Joanna; Stańczak, Joanna

    2014-12-01

    Tick-borne encephalitis virus (TBEV) (Flaviviridae, Flavivirus) is an arthropod-borne virus, an etiologic agent of tick-borne encephalitis (TBE), a human infection involving the central nervous system. The disease is endemic in a large region in Eurasia, where it is transmitted mainly by Ixodes ricinus and Ixodes persulcatus ticks. It is known that also Dermacentor reticulatus is involved in circulation of TBEV. However, the current knowledge of D. reticulatus importance in TBE epidemiology is still insufficient. A total of 471 adult D. reticulatus ticks were collected by flagging vegetation in the Białowieża Primeval Forest, Biebrza National Park, Masurian Landscape Park (North-Eastern Poland) and in the city of Warsaw in the years 2007-2010. All collected ticks were examined individually for the presence of RNA of TBEV using nested RT-PCR assay. Positive results were noted in all investigated localities with the infection rate ranging from 0.99 to 12.5 % with a total mean of 2.12 %. The difference in the percentage of infective males and females was not statistically significant.

  1. Capsid, membrane and NS3 are the major viral proteins involved in autophagy induced by Japanese encephalitis virus.

    Science.gov (United States)

    Wang, Xiujin; Hou, Lei; Du, Jige; Zhou, Lei; Ge, Xinna; Guo, Xin; Yang, Hanchun

    2015-08-05

    Japanese encephalitis virus (JEV) is an important zoonotic pathogen causing viral encephalitis in human and reproductive failure in pigs. In the present study, we first examined the autophagy induced by JEV infection in host cells, and then analyzed the JEV proteins involving in autophagy induction, and further investigated the relationship between viral protein and immunity-related GTPases M (IRGM). Our results showed that JEV infection could induce autophagy in host cells and autophagy promoted the replication of JEV in vitro; the cells transfected with individual plasmid that was expressing C, M and NS3 had a significantly higher conversion of LC3-I/II, and enhanced LC3 signals with the fluorescence punctuates accumulation which was completely co-localized with LC3 and increased number of autophagosomes-like vesicles, suggesting that C, M and NS3 are the major viral proteins involving in autophagy induction upon JEV infection; the virus titer in the cells treated by the siRNA specific for IRGM had a significant decrease, and the NS3 signals in the cells transfected with the plasmid that was expressing NS3 were completely co-localized with the IRGM signals, suggesting that the NS3 of JEV could target IRGM which may play a role in the replication of JEV. Our findings help to understand the role of autophagy in JEV and other flaviviruses infections. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Tick-borne encephalitis virus infects human brain microvascular endothelial cells without compromising blood-brain barrier integrity.

    Science.gov (United States)

    Palus, Martin; Vancova, Marie; Sirmarova, Jana; Elsterova, Jana; Perner, Jan; Ruzek, Daniel

    2017-07-01

    Alteration of the blood-brain barrier (BBB) is a hallmark of tick-borne encephalitis (TBE), a life-threating human viral neuroinfection. However, the mechanism of BBB breakdown during TBE, as well as TBE virus (TBEV) entry into the brain is unclear. Here, primary human microvascular endothelial cells (HBMECs) were infected with TBEV to study interactions with the BBB. Although the number of infected cells was relatively low in culture (10 6 pfu/ml). Infection did not induce any significant changes in the expression of key tight junction proteins or upregulate the expression of cell adhesion molecules, and did not alter the highly organized intercellular junctions between HBMECs. In an in vitro BBB model, the virus crossed the BBB via a transcellular pathway without compromising the integrity of the cell monolayer. The results indicate that HBMECs may support TBEV entry into the brain without altering BBB integrity. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. A curious coincidence: mosquito biodiversity and the limits of the Japanese encephalitis virus in Australasia

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    Russell Richard C

    2007-06-01

    Full Text Available Abstract Background The mosquito Culex annulirostris Skuse (Diptera: Culicidae is the major vector of endemic arboviruses in Australia and is also responsible for the establishment of the Japanese encephalitis virus (JEV in southern Papua New Guinea (PNG as well as its incursions into northern Australia. Papua New Guinea and mainland Australia are separated by a small stretch of water, the Torres Strait, and its islands. While there has been regular JEV activity on these islands, JEV has not established on mainland Australia despite an abundance of Cx. annulirostris and porcine amplifying hosts. Despite the public health significance of this mosquito and the fact that its adults show overlapping morphology with close relative Cx. palpalis Taylor, its evolution and genetic structure remain undetermined. We address a hypothesis that there is significant genetic diversity in Cx. annulirostris and that the identification of this diversity will shed light on the paradox that JEV can cycle on an island 70 km from mainland Australia while not establishing in Australia itself. Results We sequenced 538 bp of the mitochondrial DNA cytochrome oxidase I gene from 273 individuals collected from 43 localities in Australia and the southwest Pacific region to describe the phylogeography of Cx. annulirostris and its sister species Cx. palpalis. Maximum Likelihood and Bayesian analyses reveal supporting evidence for multiple divergent lineages that display geographic restriction. Culex palpalis contained three divergent lineages geographically restricted to southern Australia, northern Australia and Papua New Guinea (PNG. Culex annulirostris contained five geographically restricted divergent lineages, with one lineage restricted to the Solomon Islands and two identified mainly within Australia while two other lineages showed distributions in PNG and the Torres Strait Islands with a southern limit at the top of Australia's Cape York Peninsula. Conclusion The

  4. Immunoblot Profile as Predictor of Toxoplasmic Encephalitis in Patients Infected with Human Immunodeficiency Virus

    Science.gov (United States)

    Leport, Catherine; Franck, Jacqueline; Chene, Genevieve; Derouin, Francis; Ecobichon, Jean-Luc; Pueyo, Sophie; Miro, Jose M.; Luft, Benjamin J.; Morlat, Philippe; Dumon, Henri

    2001-01-01

    In order to define more accurately human immunodeficiency virus-infected patients at risk of developing toxoplasmic encephalitis (TE), we assessed the prognostic significance of the anti-Toxoplasma gondii immunoglobulin G (IgG) immunoblot profile, in addition to AIDS stage, a CD4+ cell count <50/mm3, and an antibody titer ≥150 IU/ml, in patients with CD4 cell counts <200/mm3 and seropositive for T. gondii. Baseline serum samples from 152 patients included in the placebo arm of the ANRS 005-ACTG 154 trial (pyrimethamine versus placebo) were used. The IgG immunoblot profile was determined using a Toxoplasma lysate and read using the Kodak Digital Science 1D image analysis software. Mean follow-up was 15.1 months, and the 1-year incidence of TE was 15.9%. The cumulative probability of TE varied according to the type and number of anti-T. gondii IgG bands and reached 65% at 12 months for patients with IgG bands of 25 and 22 kDa. In a Cox model adjusted for age, gender, Centers for Disease Control and Prevention (CDC) clinical stage, and CD4 and CD8 cell counts, the incidence of TE was higher when the IgG 22-kDa band (hazard ratio [HR] = 5.4; P < 0.001), the IgG 25-kDa band (HR = 4.7; P < 0.001), or the IgG 69-kDa band (HR = 3.4; P < 0.001) was present and was higher for patients at CDC stage C (HR = 4.9; P < 0.001). T. gondii antibody titer and CD4 cell count were not predictive of TE. Thus, detection of IgG bands of 25, 22, and/or 69 kDa may be helpful for deciding when primary prophylaxis for TE should be started or discontinued, especially in the era of highly active antiretroviral therapy. PMID:11329461

  5. Biochemical characterization of a recombinant Japanese encephalitis virus RNA-dependent RNA polymerase

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    Kim Chan-Mi

    2007-07-01

    Full Text Available Abstract Background Japanese encephalitis virus (JEV NS5 is a viral nonstructural protein that carries both methyltransferase and RNA-dependent RNA polymerase (RdRp domains. It is a key component of the viral RNA replicase complex that presumably includes other viral nonstructural and cellular proteins. The biochemical properties of JEV NS5 have not been characterized due to the lack of a robust in vitro RdRp assay system, and the molecular mechanisms for the initiation of RNA synthesis by JEV NS5 remain to be elucidated. Results To characterize the biochemical properties of JEV RdRp, we expressed in Escherichia coli and purified an enzymatically active full-length recombinant JEV NS5 protein with a hexahistidine tag at the N-terminus. The purified NS5 protein, but not the mutant NS5 protein with an Ala substitution at the first Asp of the RdRp-conserved GDD motif, exhibited template- and primer-dependent RNA synthesis activity using a poly(A RNA template. The NS5 protein was able to use both plus- and minus-strand 3'-untranslated regions of the JEV genome as templates in the absence of a primer, with the latter RNA being a better template. Analysis of the RNA synthesis initiation site using the 3'-end 83 nucleotides of the JEV genome as a minimal RNA template revealed that the NS5 protein specifically initiates RNA synthesis from an internal site, U81, at the two nucleotides upstream of the 3'-end of the template. Conclusion As a first step toward the understanding of the molecular mechanisms for JEV RNA replication and ultimately for the in vitro reconstitution of viral RNA replicase complex, we for the first time established an in vitro JEV RdRp assay system with a functional full-length recombinant JEV NS5 protein and characterized the mechanisms of RNA synthesis from nonviral and viral RNA templates. The full-length recombinant JEV NS5 will be useful for the elucidation of the structure-function relationship of this enzyme and for the

  6. Infiltration Pattern of Blood Monocytes into the Central Nervous System during Experimental Herpes Simplex Virus Encephalitis.

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    Rafik Menasria

    Full Text Available The kinetics and distribution of infiltrating blood monocytes into the central nervous system and their involvement in the cerebral immune response together with resident macrophages, namely microglia, were evaluated in experimental herpes simplex virus 1 (HSV-1 encephalitis (HSE. To distinguish microglia from blood monocyte-derived macrophages, chimeras were generated by conditioning C57BL/6 recipient mice with chemotherapy regimen followed by transplantation of bone morrow-derived cells that expressed the green fluorescent protein. Mice were infected intranasally with a sub-lethal dose of HSV-1 (1.2 x 10(6 plaque forming units. Brains were harvested prior to and on days 4, 6, 8 and 10 post-infection for flow cytometry and immunohistochemistry analysis. The amounts of neutrophils (P < 0.05 and "Ly6C hi" inflammatory monocytes (P < 0.001 significantly increased in the CNS compared to non-infected controls on day 6 post-infection, which corresponded to more severe clinical signs of HSE. Levels decreased on day 8 for both leukocytes subpopulations (P < 0.05 for inflammatory monocytes compared to non-infected controls to reach baseline levels on day 10 following infection. The percentage of "Ly6C low" patrolling monocytes significantly increased (P < 0.01 at a later time point (day 8, which correlated with the resolution phase of HSE. Histological analysis demonstrated that blood leukocytes colonized mostly the olfactory bulb and the brainstem, which corresponded to regions where HSV-1 particles were detected. Furthermore, infiltrating cells from the monocytic lineage could differentiate into activated local tissue macrophages that express the microglia marker, ionized calcium-binding adaptor molecule 1. The lack of albumin detection in the brain parenchyma of infected mice showed that the infiltration of blood leukocytes was not necessarily related to a breakdown of the blood-brain barrier but could be the result of a functional recruitment. Thus

  7. A comparative analysis on the physicochemical properties of tick-borne encephalitis virus envelope protein residues that affect its antigenic properties

    Czech Academy of Sciences Publication Activity Database

    Bukin, Y. S.; Dzhioev, Y.; Tkachev, S. E.; Kozlova, I.; Paramonov, A. I.; Růžek, Daniel; Qu, Z.; Zlobin, V. I.

    2017-01-01

    Roč. 238, JUN 15 (2017), s. 124-132 ISSN 0168-1702 Institutional support: RVO:60077344 Keywords : tick-borne encephalitis virus * E protein * physicochemical properties amino acid residue * antigen * antibody Subject RIV: EE - Microbiology, Virology Impact factor: 2.628, year: 2016

  8. La Crosse Encephalitis Virus Infection in Field-Collected Aedes albopictus, Aedes japonicus, and Aedes triseriatus in Tennessee.

    Science.gov (United States)

    Westby, Katie M; Fritzen, Charissa; Paulsen, Dave; Poindexter, Stephanie; Moncayo, Abelardo C

    2015-09-01

    La Crosse virus (LACV) is a mosquito-borne virus and a major cause of pediatric encephalitis in the USA. La Crosse virus emerged in Tennessee and other states in the Appalachian region in 1997. We investigated LACV infection rates and seasonal abundances of the native mosquito vector, Aedes triseriatus, and 2 recently introduced mosquito species, Ae. albopictus and Ae. japonicus, in an emerging disease focus in Tennessee. Mosquitoes were collected using multiple trapping methods specific for Aedes mosquitoes at recent human case sites. Mosquito pools were tested via reverse transcriptase-polymerase chain reaction (RT-PCR) of the S segment to detect multiple Bunyamwera and California serogroup viruses, including LACV, as well as real-time RT-PCR of the M segment. A total of 54 mosquito pools were positive, including wild-caught adult females and laboratory-reared adults, demonstrating transovarial transmission in all 3 species. Maximum likelihood estimates (per 1,000 mosquitoes) were 2.72 for Ae. triseriatus, 3.01 for Ae. albopictus, and 0.63 for Ae. japonicus. We conclude that Ae. triseriatus and Ae. albopictus are important LACV vectors and that Ae. japonicus also may be involved in virus maintenance and transmission.

  9. [Immunochip for differentiation of IgG to tick-borne encephalitis and West Nile fever viruses].

    Science.gov (United States)

    Pomelova, V G; Bychenkova, T A; Bekman, N I; Osin, N S

    2010-01-01

    To demonstrate the possibility of development of test based on phosphorescent analysis (PHOSPHAN) for simultaneous identification and differentiation of specific IgG to tick-borne encephalitis (TBE) and West Nile fever (WNF) viruses. Twenty six serum samples from patients with TBE, twenty five from WNF, and sixty six fromclinically healthy donors were used for the study. Immunologic analysis was performed in plate wells with active microzones "printed" on the wells' bottom and corresponding the complex of virus-specific antigens with immobilized monoclonal antibodies; internal control of specificity was included in each well. Species specificity of antibodies was determined on the basis of not less than 2-fold elevation of value of positivity coefficient (P/N) of sample studied with homologous antigen compared to heterologous one. PHOSPHAN provides simultaneous detection of IgG in human serum to two related flaviviruses: TBE and WNF viruses. Usage of P/N criterion assessed with homologous and heterologous antigen allowed correct determination of species specificity of antibodies in 90% of serum samples from patients with TBE and WNF CONCLUSION: PHOSPHAN allows to detect and differentiate IgG to TBE and WNF viruses during testing of one serum sample in one plate well without decrease of sensitivity compared to enzyme immunoassay with separated testing of samples on two viruses. This provides savings of biomaterial, which is an advantage compared to enzyme immunoassay.

  10. Characterization of infectious Murray Valley encephalitis virus derived from a stably cloned genome-length cDNA.

    Science.gov (United States)

    Hurrelbrink, R J; Nestorowicz, A; McMinn, P C

    1999-12-01

    An infectious cDNA clone of Murray Valley encephalitis virus prototype strain 1-51 (MVE-1-51) was constructed by stably inserting genome-length cDNA into the low-copy-number plasmid vector pMC18. Designated pMVE-1-51, the clone consisted of genome-length cDNA of MVE-1-51 under the control of a T7 RNA polymerase promoter. The clone was constructed by using existing components of a cDNA library, in addition to cDNA of the 3' terminus derived by RT-PCR of poly(A)-tailed viral RNA. Upon comparison with other flavivirus sequences, the previously undetermined sequence of the 3' UTR was found to contain elements conserved throughout the genus FLAVIVIRUS: RNA transcribed from pMVE-1-51 and subsequently transfected into BHK-21 cells generated infectious virus. The plaque morphology, replication kinetics and antigenic profile of clone-derived virus (CDV-1-51) was similar to the parental virus in vitro. Furthermore, the virulence properties of CDV-1-51 and MVE-1-51 (LD(50) values and mortality profiles) were found to be identical in vivo in the mouse model. Through site-directed mutagenesis, the infectious clone should serve as a valuable tool for investigating the molecular determinants of virulence in MVE virus.

  11. Treatment of viral encephalitis.

    Science.gov (United States)

    Domingues, Renan Barros

    2009-03-01

    Several viruses may cause central nervous system diseases with a broad range of clinical manifestations. The time course of the viral encephalitis can be acute, subacute, or chronic. Pathologically there are encephalitis with direct viral entry into the CNS in which brain parenchyma exhibits neuronal damaging and viral antigens and there are postinfectious autoimmune encephalitis associated with systemic viral infections with brain tissue presenting perivascular aggregation of immune cells and myelin damaging. Some virus affect previously healthy individuals while others produce encephalitis among imunocompromised ones. Factors such evolving lifestyles and ecological changes have had a considerable impact on the epidemiology of some viral encephalitis [e.g. West-Nile virus, and Japanese B virus]. Citomegalovirus and JC virus are examples of infections of the brain that have been seen more frequently because they occur in immunocompromised patients. In the other hand many scientific achievements in neuroimaging, molecular diagnosis, antiviral therapy, immunomodulatory treatments, and neurointensive care have allowed more precise and earlier diagnoses and more efficient treatments, resulting in improved outcomes. In this article, we will present the current drug options in the management of the main acute and chronic viral infection of the central nervous system of immunocompetent and immunocompromised adults, focusing on drugs mechanisms of action, efficacy, and side effects. The early diagnosis and correct management of such diseases can reduce mortality and neurological sequelae; however, even with recent treatment advances, potentially devastating outcomes are still possible.

  12. Exploring Genomic, Geographic and Virulence Interactions among Epidemic and Non-Epidemic St. Louis Encephalitis Virus (Flavivirus Strains.

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    Luis A Diaz

    Full Text Available St. Louis encephalitis virus (SLEV is a re-emerging arbovirus in South America. In 2005, an encephalitis outbreak caused by SLEV was reported in Argentina. The reason for the outbreak remains unknown, but may have been related to virological factors, changes in vectors populations, avian amplifying hosts, and/or environmental conditions. The main goal of this study was to characterize the complete genome of epidemic and non-epidemic SLEV strains from Argentina. Seventeen amino acid changes were detected; ten were non-conservative and located in proteins E, NS1, NS3 and NS5. Phylogenetic analysis showed two major clades based on geography: the North America and northern Central America (NAnCA clade and the South America and southern Central America (SAsCA clade. Interestingly, the presence of SAsCA genotype V SLEV strains in the NAnCA clade was reported in California, Florida and Texas, overlapping with known bird migration flyways. This work represents the first step in understanding the molecular mechanisms underlying virulence and biological variation among SLEV strains.

  13. Prevalence of tick-borne encephalitis virus in Ixodes ricinus ticks from three islands in north-western Norway.

    Science.gov (United States)

    Paulsen, Katrine M; Pedersen, Benedikte N; Soleng, Arnulf; Okbaldet, Yohannes B; Pettersson, John H-O; Dudman, Susanne G; Ottesen, Preben; Vik, Inger Sofie Samdal; Vainio, Kirsti; Andreassen, Åshild

    2015-09-01

    Tick-borne encephalitis (TBE) is the most important viral tick-borne disease in Europe and can cause severe disease in humans. In Norway, human cases have been reported only from the southern coast. The aim of this study was to investigate the prevalence of tick-borne encephalitis virus (TBEV) in questing Ixodes ricinus ticks from the north-western part of Norway. A total of 4509 ticks were collected by flagging in May and June 2014. A subpopulation of 2220 nymphs and 162 adult ticks were analysed by real-time PCR and positive samples were confirmed by pyrosequencing. The estimated prevalence of TBEV was 3.08% among adult ticks from Sekken in Møre og Romsdal County and 0.41% among nymphs from both Hitra and Frøya in Sør-Trøndelag County. This study indicates that TBEV might be more widespread than the distribution of reported human cases suggests. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  14. Tick-Borne Encephalitis Virus Habitats in North East Germany: Reemergence of TBEV in Ticks after 15 Years of Inactivity

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    Silvius Frimmel

    2014-01-01

    Full Text Available The incidence of tick-borne encephalitis has risen in Europe since 1990 and the tick-borne encephalitis virus (TBEV has been documented to be spreading into regions where it was not previously endemic. In Mecklenburg-West Pomerania, a federal state in Northern Germany, TBEV was not detectable in over 16,000 collected ticks between 1992 and 2004. Until 2004, the last human case of TBE in the region was reported in 1985. Following the occurrence of three autochthonous human cases of TBE after 2004, however, we collected ticks from the areas in which the infections were contracted. To increase the chance of detecting TBEV-RNA, some of the ticks were fed on mice. Using nested RT-PCR, we were able to confirm the presence of TBEV in ticks for the first time after 15 years. A phylogenetic analysis revealed a close relationship between the sequences we obtained and a TBEV sequence from Mecklenburg-East Pomerania published in 1992 and pointed to the reemergence of a natural focus of TBEV after years of low activity. Our results imply that natural foci of TBEV may either persist at low levels of activity for years or reemerge through the agency of migrating birds.

  15. Reconsidering the classification of tick-borne encephalitis virus within the Siberian subtype gives new insights into its evolutionary history.

    Science.gov (United States)

    Kovalev, S Y; Mukhacheva, T A

    2017-11-01

    Tick-borne encephalitis is widespread in Eurasia and transmitted by Ixodes ticks. Classification of its causative agent, tick-borne encephalitis virus (TBEV), includes three subtypes, namely Far-Eastern, European, and Siberian (TBEV-Sib), as well as a group of 886-84-like strains with uncertain taxonomic status. TBEV-Sib is subdivided into three phylogenetic lineages: Baltic, Asian, and South-Siberian. A reason to reconsider TBEV-Sib classification was the analysis of 186 nucleotide sequences of an E gene fragment submitted to GenBank during the last two years. Within the South-Siberian lineage, we have identified a distinct group with prototype strains Aina and Vasilchenko as an individual lineage named East-Siberian. The analysis of reclassified lineages has promoted a new model of the evolutionary history of TBEV-Sib lineages and TBEV-Sib as a whole. Moreover, we present arguments supporting separation of 886-84-like strains into an individual TBEV subtype, which we propose to name Baikalian (TBEV-Bkl). Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Serological Prevalence Against Japanese Encephalitis Virus-Serocomplex Flaviviruses in Commensal and Field Rodents in South China.

    Science.gov (United States)

    Chen, Shao-Wei; Jiang, Li-Na; Zhong, Xue-Shan; Zheng, Xue-Yan; Ma, Shu-Juan; Xiong, Yi-Quan; Zhou, Jun-Hua; Li, Xing; Ke, Xue-Mei; Zhou, Wen; Chen, Qing

    2016-12-01

    Japanese encephalitis caused by Japanese encephalitis virus (JEV) is an endemic zoonotic disease of high public health importance in the Asian Pacific region. The aim of this study was to investigate the presence of JEV infection in commensal and field rodents in South China. RNA copies of JEV were detected in brain samples of rodents using real-time RT-PCR. Detection of serum against JEV-reactive antibodies was performed using indirect enzyme-linked immunosorbent assay and microneutralization test. In total, 198 rodents were collected from Guangzhou City and Xiamen City between November 2013 and May 2014. JEV RNA was not detected in 188 brain samples. Forty-four in 96 serum samples (45.8%) were positive for JEV-reactive IgG antibodies. The prevalence of neutralizing antibodies to against JEV-reactive in these serum samples was 61.5% (24/39), with titers ranging from 1:10 to 1:56. Rodents are not known to play a role in transmission of JEV in Asia, nor is there an evidence to support a role for rodents in transmission of other related flaviviruses in China. However, in the current study, we detected evidence of JEV-reactive antibodies in large numbers of Rattus norvegicus and Rattus losea Swinhoe. Further studies of rodents as potential hosts of JEV or other related flaviviruses are warranted.

  17. Comparison of argentinean saint louis encephalitis virus non-epidemic and epidemic strain infections in an avian model.

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    Luis Adrián Diaz

    2011-05-01

    Full Text Available St. Louis encephalitis virus (SLEV, Flavivirus, Flaviviridae is an emerging mosquito-borne pathogen in South America, with human SLEV encephalitis cases reported in Argentina and Brazil. Genotype III strains of SLEV were isolated from Culex quinquefasciatus mosquitoes in Cordoba, Argentina in 2005, during the largest SLEV outbreak ever reported in South America. The present study tested the hypothesis that the recent, epidemic SLEV strain exhibits greater virulence in birds as compared with a non-epidemic genotype III strain isolated from mosquitoes in Santa Fe Province 27 years earlier. The observed differences in infection parameters between adult House sparrows (Passer domesticus that were needle-inoculated with either the epidemic or historic SLEV strain were not statistically significant. However, only the House sparrows that were infected with the epidemic strain achieved infectious-level viremia titers sufficient to infect Cx. spp. mosquitoes vectors. Furthermore, the vertebrate reservoir competence index values indicated an approximately 3-fold increase in amplification potential of House sparrows infected with the epidemic strain when pre-existing flavivirus-reactive antibodies were present, suggesting the possibility that antibody-dependent enhancement may increase the risk of avian-amplified transmission of SLEV in South America.

  18. Early detection of tick-borne encephalitis virus spatial distribution and activity in the province of Trento, northern Italy

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    Annapaola Rizzoli

    2007-05-01

    Full Text Available New human cases of tick-borne encephalitis (TBE have recently been recorded outside the recognised foci of this disease, i.e. in the province of Trento in northern Italy. In order to predict the highest risk areas for increased TBE virus activity, we have combined cross-sectional serological data, obtained from 459 domestic goats, with analysis of the autumnal cooling rate based on Moderate Resolution Imaging Spectroradiometer (MODIS land surface temperature (LST data. A significant relationship between finding antibodies against the virus in serum (seroprevalence in goats and the autumnal cooling rate was detected, indicating that the transmission intensity of the virus does not only vary spatially, but also in relation to climatic factors. Virus seroprevalence in goats was correlated with the occurrence of TBE in humans and also with the average number of forestry workers’ tick bites, demonstrating that serological screening of domestic animals, combined with an analysis of the autumnal cooling rate, can be used as early-warning predictors of TBE risk in humans.

  19. Incidence and clinical features of herpes simplex viruses (1 and 2) and varicella-zoster virus infections in an adult Korean population with aseptic meningitis or encephalitis.

    Science.gov (United States)

    Choi, Rihwa; Kim, Gyeong-Moon; Jo, Ik Joon; Sim, Min Seob; Song, Keun Jeong; Kim, Byoung Joon; Na, Duk L; Huh, Hee Jae; Kim, Jong-Won; Ki, Chang-Seok; Lee, Nam Yong

    2014-06-01

    Since there are limited data on the incidence and clinical findings of central nervous system (CNS) infection by three α-herpesviruses including human herpes simplex virus 1 (HSV-1), HSV-2 and varicella-zoster virus (VZV) in Korea, a retrospective analysis of clinical data and polymerase chain reaction (PCR) results was performed in patients who presented with suspicion of acute viral meningitis and/or encephalitis at the emergency department of a tertiary referral hospital in Seoul, Korea. During the 3-year study period, a total of 224 cerebrospinal fluid (CSF) samples from 224 patients were examined. Among the 224 patients, 135 (60.3%) patients were identified as having aseptic meningitis (n = 70, 51.9%), encephalitis (n = 41, 30.4%) or meningoencephalitis (n = 24, 17.8%) at discharge. Twenty-four (17.8%) patients were identified as having VZV meningitis (n = 16, 11.9%), VZV meningoencephalitis (n = 2, 1.5%), HSV-2 meningitis (n = 4, 3.0%), or HSV-1 encephalitis (n = 2, 1.5%). Of the 24 patients infected with the three herpesviruses, immunocompromised patients accounted for 33.3% (n = 8). Skin rashes were observed in half (n = 9) of the patients with VZV, and none with HSV-1 or HSV-2. One patient with VZV meningitis and four patients with brain parenchymal involvement had neurologic sequelae. In conclusion, three herpesviruses are important causative agents of CNS infectious disease with significant morbidity in adults, regardless of the immunologic status. Therefore, CSF should be examined for HSV-1, HSV-2, and VZV using sensitive diagnostic methods in all cases of adult patients with clinical manifestations of CNS disease in order to identify the correct etiology and to determine appropriate therapy. © 2014 Wiley Periodicals, Inc.

  20. Detection and differentiation of Japanese encephalitis virus genotype I and genotype III by reverse transcription loop-mediated isothermal amplification combined with restriction fragment length polymorphism.

    Science.gov (United States)

    Zhang, Liang; Cao, Sanjie; Wu, Rui; Zhu, Shuquan; Liu, Hanyang; Yuan, Lei; Shi, Shuangyan; Zhang, Dan; Huang, Xiaobo; Wen, Xintian; Wen, Yiping; Yan, Qigui; Huang, Yong; Ma, Xiaoping

    2015-04-01

    Japanese encephalitis (JE), which is a mosquito-borne arboviral infection, is the leading cause of viral encephalitis in Asian countries. The causative agent of JE is Japanese encephalitis virus (JEV), in which the predominant genotype has changed from genotype III (G III) to genotype I (G I). However, a method for the rapid differentiation between JEV G I and G III remains unavailable. This study aimed to establish a rapid JEV genotyping method using reverse transcription loop-mediated isothermal amplification (RT-LAMP). An Spe I site, which was located in the target sequence (C gene) of JEV G III strains but not in JEV G I strains, was selected as the RT-LAMP target. After testing 64 specimens, results showed that RT-LAMP can detect and differentiate JEV G I and G III specifically. Thus, a novel RT-LAMP system for the rapid detection and differentiation of JEV G I and G III was developed successfully.

  1. Elaboration of a clinical and paraclinical score to estimate the probability of herpes simplex virus encephalitis in patients with febrile, acute neurologic impairment.

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    Gennai, S; Rallo, A; Keil, D; Seigneurin, A; Germi, R; Epaulard, O

    2016-06-01

    Herpes simplex virus (HSV) encephalitis is associated with a high risk of mortality and sequelae, and early diagnosis and treatment in the emergency department are necessary. However, most patients present with non-specific febrile, acute neurologic impairment; this may lead clinicians to overlook the diagnosis of HSV encephalitis. We aimed to identify which data collected in the first hours in a medical setting were associated with the diagnosis of HSV encephalitis. We conducted a multicenter retrospective case-control study in four French public hospitals from 2007 to 2013. The cases were the adult patients who received a confirmed diagnosis of HSV encephalitis. The controls were all the patients who attended the emergency department of Grenoble hospital with a febrile acute neurologic impairment, without HSV detection by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF), in 2012 and 2013. A multivariable logistic model was elaborated to estimate factors significantly associated with HSV encephalitis. Finally, an HSV probability score was derived from the logistic model. We identified 36 cases and 103 controls. Factors independently associated with HSV encephalitis were the absence of past neurological history (odds ratio [OR] 6.25 [95 % confidence interval (CI): 2.22-16.7]), the occurrence of seizure (OR 8.09 [95 % CI: 2.73-23.94]), a systolic blood pressure ≥140 mmHg (OR 5.11 [95 % CI: 1.77-14.77]), and a C-reactive protein <10 mg/L (OR 9.27 [95 % CI: 2.98-28.88]). An HSV probability score was calculated summing the value attributed to each independent factor. HSV encephalitis diagnosis may benefit from the use of this score based upon some easily accessible data. However, diagnostic evocation and probabilistic treatment must remain the rule.

  2. Gene Expression Profiling of Nonhuman Primates Exposed to Aerosolized Venezuelan Equine Encephalitis Virus

    Science.gov (United States)

    2007-12-01

    autoimmune demyelinating disease in mice. J Neuroimmunol 95: 43–54. Muro S, Taha R, Tsicopoulos A, Olivenstein R, Tonnel AB, Christodoulopoulos P...Army Medical Research Institute of Infectious Diseases , Fort Detrick, Frederick, MD, USA; 2Virginia Bioinformatics Institute, Bioinformatics Facility...less frequently in humans, with neurological diseases appearing in 4–14% of the cases. VEE occurs in all age groups, and fatal encephalitis is more

  3. Relationships between infection with caprine arthritis encephalitis virus, intramammary bacterial infection and somatic cell counts in dairy goats.

    Science.gov (United States)

    Sánchez, A; Contreras, A; Corrales, J C; Marco, J C

    2001-06-09

    Somatic cell counts, the bacteriological condition of the milk and antibodies against caprine arthritis encephalitis virus (CAEV) were measured monthly throughout lactation in 121 lactating goats of the Murcia-Granada breed in four commercial dairy goat herds. The prevalence of bacterial intramammary infection was 5.6 per cent and the prevalence of CAEV infection was 20.6 per cent. An analysis of variance revealed a significant effect of herd, intramammary infection and the interaction between intramammary infection and CAEV on the somatic cell count. In udder halves free of intramammary infection, the somatic cell counts were significantly lower in seronegative goats than in seropositive goats (Peffect was not present in the seropositive animals.

  4. Cotton rats and house sparrows as hosts for North and South American strains of eastern equine encephalitis virus.

    Science.gov (United States)

    Arrigo, Nicole C; Adams, A Paige; Watts, Douglas M; Newman, Patrick C; Weaver, Scott C

    2010-09-01

    Eastern equine encephalitis virus (EEEV; family Togaviridae, genus Alphavirus) is an arbovirus that causes severe disease in humans in North America and in equids throughout the Americas. The enzootic transmission cycle of EEEV in North America involves passerine birds and the ornithophilic mosquito vector, Culiseta melanura, in freshwater swamp habitats. However, the ecology of EEEV in South America is not well understood. Culex (Melanoconion) spp. mosquitoes are considered the principal vectors in Central and South America; however, a primary vertebrate host for EEEV in South America has not yet been identified. Therefore, to further assess the reservoir host potential of wild rodents and wild birds, we compared the infection dynamics of North American and South American EEEV in cotton rats (Sigmodon hispidus) and house sparrows (Passer domesticus). Our findings suggested that each species has the potential to serve as amplification hosts for North and South America EEEVs.

  5. MicroRNA-19b-3p Modulates Japanese Encephalitis Virus-Mediated Inflammation via Targeting RNF11.

    Science.gov (United States)

    Ashraf, Usama; Zhu, Bibo; Ye, Jing; Wan, Shengfeng; Nie, Yanru; Chen, Zheng; Cui, Min; Wang, Chong; Duan, Xiaodong; Zhang, Hao; Chen, Huanchun; Cao, Shengbo

    2016-05-01

    Japanese encephalitis virus (JEV) can invade the central nervous system and consequently induce neuroinflammation, which is characterized by profound neuronal cell damage accompanied by astrogliosis and microgliosis. Albeit microRNAs (miRNAs) have emerged as major regulatory noncoding RNAs with profound effects on inflammatory response, it is unknown how astrocytic miRNAs regulate JEV-induced inflammation. Here, we found the involvement of miR-19b-3p in regulating the JEV-induced inflammatory responsein vitroandin vivo The data demonstrated that miR-19b-3p is upregulated in cultured cells and mouse brain tissues during JEV infection. Overexpression of miR-19b-3p led to increased production of inflammatory cytokines, including tumor necrosis factor alpha, interleukin-6, interleukin-1β, and chemokine (C-C motif) ligand 5, after JEV infection, whereas knockdown of miR-19b-3p had completely opposite effects. Mechanistically, miR-19b-3p modulated the JEV-induced inflammatory response via targeting ring finger protein 11, a negative regulator of nuclear factor kappa B signaling. We also found that inhibition of ring finger protein 11 by miR-19b-3p resulted in accumulation of nuclear factor kappa B in the nucleus, which in turn led to higher production of inflammatory cytokines.In vivosilencing of miR-19b-3p by a specific antagomir reinvigorates the expression level of RNF11, which in turn reduces the production of inflammatory cytokines, abrogates gliosis and neuronal cell death, and eventually improves the survival rate in the mouse model. Collectively, our results demonstrate that miR-19b-3p positively regulates the JEV-induced inflammatory response. Thus, miR-19b-3p targeting may constitute a thought-provoking approach to rein in JEV-induced inflammation. Japanese encephalitis virus (JEV) is one of the major causes of acute encephalitis in humans worldwide. The pathological features of JEV-induced encephalitis are inflammatory reactions and neurological diseases

  6. A Feasibility Study of Quantifying Longitudinal Brain Changes in Herpes Simplex Virus (HSV Encephalitis Using Magnetic Resonance Imaging (MRI and Stereology.

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    Sylviane Defres

    Full Text Available To assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV encephalitis as a preliminary to a trial of corticosteroid therapy.The study analysed serially acquired magnetic resonance images (MRI, of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR images using stereology in conjunction with point counting.Temporal lobe volumes increased on average by 1.6% (standard deviation (SD 11% in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids.This study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis.

  7. A Feasibility Study of Quantifying Longitudinal Brain Changes in Herpes Simplex Virus (HSV) Encephalitis Using Magnetic Resonance Imaging (MRI) and Stereology.

    Science.gov (United States)

    Defres, Sylviane; Keller, Simon S; Das, Kumar; Vidyasagar, Rishma; Parkes, Laura M; Burnside, Girvan; Griffiths, Michael; Kopelman, Michael; Roberts, Neil; Solomon, Tom

    2017-01-01

    To assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV) encephalitis as a preliminary to a trial of corticosteroid therapy. The study analysed serially acquired magnetic resonance images (MRI), of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR) images using stereology in conjunction with point counting. Temporal lobe volumes increased on average by 1.6% (standard deviation (SD 11%) in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids. This study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis.

  8. Specificity and dynamics of effector and memory CD8 T cell responses in human tick-borne encephalitis virus infection.

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    Kim Blom

    2015-01-01

    Full Text Available Tick-borne encephalitis virus (TBEV is transferred to humans by ticks. The virus causes tick-borne encephalitis (TBE with symptoms such as meningitis and meningoencephalitis. About one third of the patients suffer from long-lasting sequelae after clearance of the infection. Studies of the immune response during TBEV-infection are essential to the understanding of host responses to TBEV-infection and for the development of therapeutics. Here, we studied in detail the primary CD8 T cell response to TBEV in patients with acute TBE. Peripheral blood CD8 T cells mounted a considerable response to TBEV-infection as assessed by Ki67 and CD38 co-expression. These activated cells showed a CD45RA-CCR7-CD127- phenotype at day 7 after hospitalization, phenotypically defining them as effector cells. An immunodominant HLA-A2-restricted TBEV epitope was identified and utilized to study the characteristics and temporal dynamics of the antigen-specific response. The functional profile of TBEV-specific CD8 T cells was dominated by variants of mono-functional cells as the effector response matured. Antigen-specific CD8 T cells predominantly displayed a distinct Eomes+Ki67+T-bet+ effector phenotype at the peak of the response, which transitioned to an Eomes-Ki67-T-bet+ phenotype as the infection resolved and memory was established. These transcription factors thus characterize and discriminate stages of the antigen-specific T cell response during acute TBEV-infection. Altogether, CD8 T cells responded strongly to acute TBEV infection and passed through an effector phase, prior to gradual differentiation into memory cells with distinct transcription factor expression-patterns throughout the different phases.

  9. Infection of human endothelial cells by Japanese encephalitis virus: increased expression and release of soluble HLA-E.

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    Shwetank

    Full Text Available Japanese encephalitis virus (JEV is a single stranded RNA virus that infects the central nervous system leading to acute encephalitis in children. Alterations in brain endothelial cells have been shown to precede the entry of this flavivirus into the brain, but infection of endothelial cells by JEV and their consequences are still unclear. Productive JEV infection was established in human endothelial cells leading to IFN-β and TNF-α production. The MHC genes for HLA-A, -B, -C and HLA-E antigens were upregulated in human brain microvascular endothelial cells, the endothelial-like cell line, ECV 304 and human foreskin fibroblasts upon JEV infection. We also report the release/shedding of soluble HLA-E (sHLA-E from JEV infected human endothelial cells for the first time. This shedding of sHLA-E was blocked by an inhibitor of matrix metalloproteinases (MMP. In addition, MMP-9, a known mediator of HLA solubilisation was upregulated by JEV. In contrast, human fibroblasts showed only upregulation of cell-surface HLA-E. Addition of UV inactivated JEV-infected cell culture supernatants stimulated shedding of sHLA-E from uninfected ECV cells indicating a role for soluble factors/cytokines in the shedding process. Antibody mediated neutralization of TNF-α as well as IFNAR receptor together not only resulted in inhibition of sHLA-E shedding from uninfected cells, it also inhibited HLA-E and MMP-9 gene expression in JEV-infected cells. Shedding of sHLA-E was also observed with purified TNF-α and IFN-β as well as the dsRNA analog, poly (I:C. Both IFN-β and TNF-α further potentiated the shedding when added together. The role of soluble MHC antigens in JEV infection is hitherto unknown and therefore needs further investigation.

  10. Full genome sequences and molecular characterization of tick-borne encephalitis virus strains isolated from human patients.

    Science.gov (United States)

    Formanová, Petra; Černý, Jiří; Bolfíková, Barbora Černá; Valdés, James J; Kozlova, Irina; Dzhioev, Yuri; Růžek, Daniel

    2015-02-01

    Tick-borne encephalitis virus (TBEV) causes tick-borne encephalitis (TBE), one of the most important human neuroinfections across Eurasia. Up to date, only three full genome sequences of human European TBEV isolates are available, mostly due to difficulties with isolation of the virus from human patients. Here we present full genome characterization of an additional five low-passage TBEV strains isolated from human patients with severe forms of TBE. These strains were isolated in 1953 within Central Bohemia in the former Czechoslovakia, and belong to the historically oldest human TBEV isolates in Europe. We demonstrate here that all analyzed isolates are distantly phylogenetically related, indicating that the emergence of TBE in Central Europe was not caused by one predominant strain, but rather a pool of distantly related TBEV strains. Nucleotide identity between individual sequenced TBEV strains ranged from 97.5% to 99.6% and all strains shared large deletions in the 3' non-coding region, which has been recently suggested to be an important determinant of virulence. The number of unique amino acid substitutions varied from 3 to 9 in individual isolates, but no characteristic amino acid substitution typical exclusively for all human TBEV isolates was identified when compared to the isolates from ticks. We did, however, correlate that the exploration of the TBEV envelope glycoprotein by specific antibodies were in close proximity to these unique amino acid substitutions. Taken together, we report here the largest number of patient-derived European TBEV full genome sequences to date and provide a platform for further studies on evolution of TBEV since the first emergence of human TBE in Europe. Copyright © 2014 Elsevier GmbH. All rights reserved.

  11. The evidence of porcine hemagglutinating encephalomyelitis virus induced nonsuppurative encephalitis as the cause of death in piglets

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    Zi Li

    2016-09-01

    Full Text Available An acute outbreak of porcine hemagglutinating encephalomyelitis virus (PHEV infection in piglets, characterized with neurological symptoms, vomiting, diarrhea, and wasting, occurred in China. Coronavirus-like particles were observed in the homogenized tissue suspensions of the brain of dead piglets by electron microscopy, and a wild PHEV strain was isolated, characterized, and designated as PHEV-CC14. Histopathologic examinations of the dead piglets showed characteristics of non-suppurative encephalitis, and some neurons in the cerebral cortex were degenerated and necrotic, and neuronophagia. Similarly, mice inoculated with PHEV-CC14 were found to have central nervous system (CNS dysfunction, with symptoms of depression, arched waists, standing and vellicating front claws. Furthmore, PHEV-positive labeling of neurons in cortices of dead piglets and infected mice supported the viral infections of the nervous system. Then, the major structural genes of PHEV-CC14 were sequenced and phylogenetically analyzed, and the strain shared 95%–99.2% nt identity with the other PHEV strains available in GenBank. Phylogenetic analysis clearly proved that the wild strain clustered into a subclass with a HEV-JT06 strain. These findings suggested that the virus had a strong tropism for CNS, in this way, inducing nonsuppurative encephalitis as the cause of death in piglets. Simultaneously, the predicted risk of widespread transmission showed a certain variation among the PHEV strains currently circulating around the world. Above all, the information presented in this study can not only provide good reference for the experimental diagnosis of PHEV infection for pig breeding, but also promote its new effective vaccine development.

  12. A Japanese encephalitis virus genotype 5 molecular clone is highly neuropathogenic in a mouse model: impact of the structural protein region on virulence.

    Science.gov (United States)

    de Wispelaere, Mélissanne; Frenkiel, Marie-Pascale; Desprès, Philippe

    2015-06-01

    Japanese encephalitis virus (JEV) strains can be separated into 5 genotypes (g1 to g5) based on sequence similarity. JEV g5 strains have been rarely isolated and are poorly characterized. We report here the full characterization of a g5 virus generated using a cDNA-based technology and its comparison with a widely studied g3 strain. We did not observe any major differences between those viruses when their infectious cycles were studied in various cell lines in vitro. Interestingly, the JEV g5 strain was highly pathogenic when inoculated to BALB/c mice, which are known to be largely resistant to JEV g3 infection. The study of chimeric viruses between JEV g3 and g5 showed that there was a poor viral clearance of viruses that express JEV g5 structural proteins in BALB/c mice blood, which correlated with viral invasion of the central nervous system and encephalitis. In addition, using an in vitro model of the blood-brain barrier, we were able to show that JEV g5 does not have an enhanced capacity for entering the central nervous system, compared to JEV g3. Overall, in addition to providing a first characterization of the understudied JEV g5, our work highlights the importance of sustaining an early viremia in the development of JEV encephalitis. Genotype 5 viruses are genetically and serologically distinct from other JEV genotypes and can been associated with human encephalitis, which warrants the need for their characterization. In this study, we characterized the in vitro and in vivo properties of a JEV g5 strain and showed that it was more neuropathogenic in a mouse model than a well-characterized JEV g3 strain. The enhanced virulence of JEV g5 was associated with poor viral clearance but not with enhanced crossing of the blood-brain barrier, thus providing new insights into JEV pathogenesis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Virus detection in questing ticks is not a sensitive indicator for risk assessment of tick-borne encephalitis in humans.

    Science.gov (United States)

    Stefanoff, P; Pfeffer, M; Hellenbrand, W; Rogalska, J; Rühe, F; Makówka, A; Michalik, J; Wodecka, B; Rymaszewska, A; Kiewra, D; Baumann-Popczyk, A; Dobler, G

    2013-05-01

    Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted arbovirus causing human disease in Europe, but information on its endemic occurrence varies between countries because of differences in surveillance systems. Objective data are necessary to ascertain the disease risk for vaccination recommendations and other public health interventions. In two independent, separately planned projects, we used real-time RT-PCR to detect TBE virus in questing ticks. In Poland, 32 sampling sites were selected in 10 administrative districts located in regions where sporadic TBE cases were reported. In Germany, 18 sampling sites were selected in two districts located in a region with high TBE incidence. Altogether, >16,000 ticks were tested by real-time RT-PCR, with no sample testing positive for TBEV. A systematic search for published studies on TBEV prevalence in ticks in Poland and Germany also suggested that testing large numbers of collected ticks could not consistently assure virus detection in known endemic foci. Although assignment of results to administrative regions is essential for TBE risk mapping, this was possible in only 10 (investigating 22,417 ticks) of 15 published studies (>50,000 ticks) identified. We conclude that the collection and screening of ticks by real-time RT-PCR cannot be recommended for assessment of human TBE risk. Alternative methods of environmental TBEV monitoring should be considered, such as serological monitoring of rodents or other wildlife. © 2012 Blackwell Verlag GmbH.

  14. Bispidine-amino acid conjugates act as a novel scaffold for the design of antivirals that block Japanese encephalitis virus replication.

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    V Haridas

    Full Text Available Japanese encephalitis virus (JEV is a major cause of viral encephalitis in South and South-East Asia. Lack of antivirals and non-availability of affordable vaccines in these endemic areas are a major setback in combating JEV and other closely related viruses such as West Nile virus and dengue virus. Protein secondary structure mimetics are excellent candidates for inhibiting the protein-protein interactions and therefore serve as an attractive tool in drug development. We synthesized derivatives containing the backbone of naturally occurring lupin alkaloid, sparteine, which act as protein secondary structure mimetics and show that these compounds exhibit antiviral properties.In this study we have identified 3,7-diazabicyclo[3.3.1]nonane, commonly called bispidine, as a privileged scaffold to synthesize effective antiviral agents. We have synthesized derivatives of bispidine conjugated with amino acids and found that hydrophobic amino acid residues showed antiviral properties against JEV. We identified a tryptophan derivative, Bisp-W, which at 5 µM concentration inhibited JEV infection in neuroblastoma cells by more than 100-fold. Viral inhibition was at a stage post-entry and prior to viral protein translation possibly at viral RNA replication. We show that similar concentration of Bisp-W was capable of inhibiting viral infection of two other encephalitic viruses namely, West Nile virus and Chandipura virus.We have demonstrated that the amino-acid conjugates of 3,7-diazabicyclo[3.3.1]nonane can serve as a molecular scaffold for development of potent antivirals against encephalitic viruses. Our findings will provide a novel platform to develop effective inhibitors of JEV and perhaps other RNA viruses causing encephalitis.

  15. Alphavirus vector-based replicon particles expressing multivalent cross-protective Lassa virus glycoproteins.

    Science.gov (United States)

    Wang, Min; Jokinen, Jenny; Tretyakova, Irina; Pushko, Peter; Lukashevich, Igor S

    2018-01-29

    Lassa virus (LASV) is the most prevalent rodent-borne arenavirus circulated in West Africa. With population at risk from Senegal to Nigeria, LASV causes Lassa fever and is responsible for thousands of deaths annually. High genetic diversity of LASV is one of the challenges for vaccine R&D. We developed multivalent virus-like particle vectors (VLPVs) derived from the human Venezuelan equine encephalitis TC-83 IND vaccine (VEEV) as the next generation of alphavirus-based bicistronic RNA replicon particles. The genes encoding VEEV structural proteins were replaced with LASV glycoproteins (GPC) from distantly related clades I and IV with individual 26S promoters. Bicistronic RNA replicons encoding wild-type LASV GPC (GPCwt) and C-terminally deleted, non-cleavable modified glycoprotein (ΔGPfib), were encapsidated into VLPV particles using VEEV capsid and glycoproteins provided in trans. In transduced cells, VLPVs induced simultaneous expression of LASV GPCwt and ΔGPfib from 26S alphavirus promoters. LASV ΔGPfib was predominantly expressed as trimers, accumulated in the endoplasmic reticulum, induced ER stress and apoptosis promoting antigen cross-priming. VLPV vaccines were immunogenic and protective in mice and upregulated CD11c + /CD8 + dendritic cells playing the major role in cross-presentation. Notably, VLPV vaccination resulted in induction of cross-reactive multifunctional T cell responses after stimulation of immune splenocytes with peptide cocktails derived from LASV from clades I-IV. Multivalent RNA replicon-based LASV vaccines can be applicable for first responders, international travelers visiting endemic areas, military and lab personnel. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Multiplication and distribution of type 2 dengue and Japanese encephalitis viruses in Toxorhynchites splendens after intrathoracic inoculation.

    Science.gov (United States)

    Yamamoto, N; Kimura, T; Ohyama, A

    1987-01-01

    The nonhematophagous mosquito Toxorhynchites (Tx.) splendens was found to be the most susceptible to type 2 dengue (D-2) and Japanese encephalitis (JEV) viruses among three hosts examined by virus titration and replication assays. After inoculation with D-2, the number of viral antigen positive cells in the head, thorax and abdomen increased up to day 15 and D-2 reached the maximum titer of 8.4 log10 PFU/g in the head on day 15. Hemocytes were the earliest cell type that could be detected as D-2 antigen positive on day 2. Multiplication of JEV was faster than that of D-2 in the mosquito. The number of JEV antigen positive cells in each part of the mosquito increased up to day 3, JEV reaching the maximum titer of 8.0 log10 PFU/g in the abdomen on day 3. Hemocytes and fat body cells (FBC) could be detected as JEV antigen positive cells on day 1. The time course of D-2 and JEV infection suggested that intrathoracically inoculated viruses were probably initially phagocytosed by hemocytes and/or FBC, and multiplied primarily in their cytoplasm. The infected hemocytes were then transported by the flow of body fluid and viruses were disseminated to other susceptible organs, such as ganglia, salivary glands, etc. The results obtained indicate that the course of infection of D-2 and JEV in Tx. splendens is similar to that in vector mosquitoes. Tx. splendens is therefore very useful for the study of these viruses.

  17. Tick-Borne Encephalitis Virus Replication, Intracellular Trafficking, and Pathogenicity in Human Intestinal Caco-2 Cell Monolayers

    Science.gov (United States)

    Möller, Lars; Schulzke, Joerg D.; Niedrig, Matthias; Bücker, Roland

    2014-01-01

    Tick-borne encephalitis virus (TBEV) is one of the most important vector-borne viruses in Europe and Asia. Its transmission mainly occurs by the bite of an infected tick. However, consuming milk products from infected livestock animals caused TBEV cases. To better understand TBEV transmission via the alimentary route, we studied viral infection of human intestinal epithelial cells. Caco-2 cells were used to investigate pathological effects of TBEV infection. TBEV-infected Caco-2 monolayers showed morphological changes including cytoskeleton rearrangements and cytoplasmic vacuolization. Ultrastructural analysis revealed dilatation of the rough endoplasmic reticulum and further enlargement to TBEV containing caverns. Caco-2 monolayers maintained an intact epithelial barrier with stable transepithelial electrical resistance (TER) during early stage of infection. Concomitantly, viruses were detected in the basolateral medium, implying a transcytosis pathway. When Caco-2 cells were pre-treated with inhibitors of cellular pathways of endocytosis TBEV cell entry was efficiently blocked, suggesting that actin filaments (Cytochalasin) and microtubules (Nocodazole) are important for PI3K-dependent (LY294002) virus endocytosis. Moreover, experimental fluid uptake assay showed increased intracellular accumulation of FITC-dextran containing vesicles. Immunofluorescence microscopy revealed co-localization of TBEV with early endosome antigen-1 (EEA1) as well as with sorting nexin-5 (SNX5), pointing to macropinocytosis as trafficking mechanism. In the late phase of infection, further evidence was found for translocation of virus via the paracellular pathway. Five days after infection TER was slightly decreased. Epithelial barrier integrity was impaired due to increased epithelial apoptosis, leading to passive viral translocation. These findings illuminate pathomechanisms in TBEV infection of human intestinal epithelial cells and viral transmission via the alimentary route. PMID

  18. Tick-borne encephalitis virus replication, intracellular trafficking, and pathogenicity in human intestinal Caco-2 cell monolayers.

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    Chao Yu

    Full Text Available Tick-borne encephalitis virus (TBEV is one of the most important vector-borne viruses in Europe and Asia. Its transmission mainly occurs by the bite of an infected tick. However, consuming milk products from infected livestock animals caused TBEV cases. To better understand TBEV transmission via the alimentary route, we studied viral infection of human intestinal epithelial cells. Caco-2 cells were used to investigate pathological effects of TBEV infection. TBEV-infected Caco-2 monolayers showed morphological changes including cytoskeleton rearrangements and cytoplasmic vacuolization. Ultrastructural analysis revealed dilatation of the rough endoplasmic reticulum and further enlargement to TBEV containing caverns. Caco-2 monolayers maintained an intact epithelial barrier with stable transepithelial electrical resistance (TER during early stage of infection. Concomitantly, viruses were detected in the basolateral medium, implying a transcytosis pathway. When Caco-2 cells were pre-treated with inhibitors of cellular pathways of endocytosis TBEV cell entry was efficiently blocked, suggesting that actin filaments (Cytochalasin and microtubules (Nocodazole are important for PI3K-dependent (LY294002 virus endocytosis. Moreover, experimental fluid uptake assay showed increased intracellular accumulation of FITC-dextran containing vesicles. Immunofluorescence microscopy revealed co-localization of TBEV with early endosome antigen-1 (EEA1 as well as with sorting nexin-5 (SNX5, pointing to macropinocytosis as trafficking mechanism. In the late phase of infection, further evidence was found for translocation of virus via the paracellular pathway. Five days after infection TER was slightly decreased. Epithelial barrier integrity was impaired due to increased epithelial apoptosis, leading to passive viral translocation. These findings illuminate pathomechanisms in TBEV infection of human intestinal epithelial cells and viral transmission via the alimentary

  19. Tick-borne encephalitis virus replication, intracellular trafficking, and pathogenicity in human intestinal Caco-2 cell monolayers.

    Science.gov (United States)

    Yu, Chao; Achazi, Katharina; Möller, Lars; Schulzke, Joerg D; Niedrig, Matthias; Bücker, Roland

    2014-01-01

    Tick-borne encephalitis virus (TBEV) is one of the most important vector-borne viruses in Europe and Asia. Its transmission mainly occurs by the bite of an infected tick. However, consuming milk products from infected livestock animals caused TBEV cases. To better understand TBEV transmission via the alimentary route, we studied viral infection of human intestinal epithelial cells. Caco-2 cells were used to investigate pathological effects of TBEV infection. TBEV-infected Caco-2 monolayers showed morphological changes including cytoskeleton rearrangements and cytoplasmic vacuolization. Ultrastructural analysis revealed dilatation of the rough endoplasmic reticulum and further enlargement to TBEV containing caverns. Caco-2 monolayers maintained an intact epithelial barrier with stable transepithelial electrical resistance (TER) during early stage of infection. Concomitantly, viruses were detected in the basolateral medium, implying a transcytosis pathway. When Caco-2 cells were pre-treated with inhibitors of cellular pathways of endocytosis TBEV cell entry was efficiently blocked, suggesting that actin filaments (Cytochalasin) and microtubules (Nocodazole) are important for PI3K-dependent (LY294002) virus endocytosis. Moreover, experimental fluid uptake assay showed increased intracellular accumulation of FITC-dextran containing vesicles. Immunofluorescence microscopy revealed co-localization of TBEV with early endosome antigen-1 (EEA1) as well as with sorting nexin-5 (SNX5), pointing to macropinocytosis as trafficking mechanism. In the late phase of infection, further evidence was found for translocation of virus via the paracellular pathway. Five days after infection TER was slightly decreased. Epithelial barrier integrity was impaired due to increased epithelial apoptosis, leading to passive viral translocation. These findings illuminate pathomechanisms in TBEV infection of human intestinal epithelial cells and viral transmission via the alimentary route.

  20. The immunogenicity of tetravalent dengue DNA vaccine in mice pre-exposed to Japanese encephalitis or Dengue virus antigens.

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    Prompetchara, Eakachai; Ketloy, Chutitorn; Keelapang, Poonsook; Sittisombut, Nopporn; Ruxrungtham, Kiat

    2015-09-01

    Asian countries are an endemic area for both dengue (DENV) and Japanese encephalitis viruses (JEV). While JEV vaccines have been used extensively in this region, DENV vaccines remains under development. Whether preexisting naturally acquired or vaccination-induced immunity against JEV may affect the immune response to dengue vaccine candidate is unclear. In this study we used mice previously immunized with JEV vaccines to evaluate the impact on dengue-specific neutralizing antibody responses to a tetravalent dengue DNA vaccine candidate (TDNA). A tetravalent cocktail of plasmids encoding pre-membrane and envelope proteins from each dengue serotype was administered into mice which had been previously primed with inactivated or live-attenuated JEV vaccines, or dengue serotype2 virus (DENV-2). Neutralizing antibody response was measured employing a plaque reduction neutralization test at two weeks after the priming and at four weeks after the second dose of the dengue tetravalent plasmids. Inactivated or live-attenuated JEV vaccines, or DENV-2 induced low levels of neutralizing antibodies against the homologous viruses (JE and dengue virus, respectively). DENV-2 injection induced also low levels of cross-reactive antibodies against DENV-1, -3 and -4. JEV vaccines have no effect on the dengue-specific neutralizing antibody responses to the subsequent TDNA immunization. Pre-exposure to DENV-2 infection increased DENV-2 specific response neutralizing antibody to two doses of TDNA plasmids by six folds, but did not affect antibody response to other serotypes. Priming with JEV vaccines did not impact on dengue virus-specific neutralizing antibody response to a dengue TDNA vaccine candidate in mice.

  1. Kinetics of cytokine profile during intraperitoneal inoculation of Japanese encephalitis virus in BALB/c mice model.

    Science.gov (United States)

    Saxena, Vandana; Mathur, Asha; Krishnani, Narendra; Dhole, Tapan N

    2008-01-01

    Infection with Japanese encephalitis virus (JEV) is mostly asymptomatic/subclinical in 90% of the individuals. Host immune response during subclinical JEV infection is poorly understood. We assessed iNOS, IFN-gamma, TNF-alpha, IL-10 and IL-4 production in spleen, brain and sera of intraperitoneally challenged BALB/c mice by RT-PCR and ELISA along with brain histopathology at different days post inoculation (d.p.i.). In spleen of virus infected mice, expression of all cytokines including iNOS mRNA were upregulated till 5d.p.i. followed by decline. At 5d.p.i., IL-10 expression outcompeted TNF-alpha, IFN-gamma and IL-4. However, in the virus infected mice sera, IL-4 production predominated over TNF-alpha and IL-10 at 5d.p.i. Conversely, cytokines expression and iNOS mRNA remained unchanged in the brain of virus infected mice from 1 to 7d.p.i. A significant increase in the cytokine expression was observed at 11d.p.i. (P<0.05) in virus infected mice brain, with the predominance of IL-10 along with the presence of meningeal inflammation and viral RNA by histology and RT-PCR, respectively. We report a biased pattern of cytokine production in sera, brain and spleen of mice intraperitoneally challenged with JEV. IL-10 exerts neuroprotective function during JEV and regulates deleterious effects of proinflammatory cytokines; however, its mechanism needs further investigation.

  2. Rab5 and Rab11 Are Required for Clathrin-Dependent Endocytosis of Japanese Encephalitis Virus in BHK-21 Cells.

    Science.gov (United States)

    Liu, Chun-Chun; Zhang, Yun-Na; Li, Zhao-Yao; Hou, Jin-Xiu; Zhou, Jing; Kan, Lin; Zhou, Bin; Chen, Pu-Yan

    2017-10-01

    During infection Japanese encephalitis virus (JEV) generally enters host cells via receptor-mediated clathrin-dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and postinternalization of JEV were analyzed using biochemical inhibitors, RNA interference, and dominant negative (DN) mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol but not on caveolae or macropinocytosis. The effect on JEV infection of dominant negative (DN) mutants of four Rab proteins that regulate endosomal trafficking was examined. Expression of DN Rab5 and DN Rab11, but not DN Rab7 and DN Rab9, significantly inhibited JEV replication. These results were further tested by silencing Rab5 or Rab11 expression before viral infection. Confocal microscopy showed that virus particles colocalized with Rab5 or Rab11 within 15 min after virus entry, suggesting that after internalization JEV moves to early and recycling endosomes before the release of the viral genome. Our findings demonstrate the roles of Rab5 and Rab11 on JEV infection of BHK-21 cells through the endocytic pathway, providing new insights into the life cycle of flaviviruses. IMPORTANCE Although Japanese encephalitis virus (JEV) utilizes different endocytic pathways depending on the cell type being infected, the detailed mechanism of its entry into BHK-21 cells is unknown. Understanding the process of JEV endocytosis and postinternalization will advance our knowledge of JEV infection and pathogenesis as well as provide potential novel drug targets for antiviral intervention. With this objective, we used systematic approaches to dissect this process. The results show that entry of JEV into BHK-21 cells requires a low-pH environment and that the process occurs through dynamin-, actin-, and cholesterol-dependent clathrin-mediated endocytosis that

  3. Viral encephalitis

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    Marcus Tulius T Silva

    2013-09-01

    Full Text Available While systemic viral infections are exceptionally common, symptomatic viral infections of the brain parenchyma itself are very rare, but a serious neurologic condition. It is estimated that viral encephalitis occurs at a rate of 1.4 cases per 100.000 inhabitants. Geography is a major determinant of encephalitis caused by vector-borne pathogens. A diagnosis of viral encephalitis could be a challenge to the clinician, since almost 70% of viral encephalitis cases are left without an etiologic agent identified. In this review, the most common viral encephalitis will be discussed, with focus on ecology, diagnosis, and clinical management.

  4. Serological evidence of widespread West Nile virus and Japanese encephalitis virus infection in native domestic ducks (Anas platyrhynchos var domesticus) in Kuttanad region, Kerala, India.

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    Kalaiyarasu, Semmannan; Mishra, Niranjan; Khetan, Rohit Kumar; Singh, Vijendra Pal

    2016-10-01

    Birds can act as reservoirs of West Nile virus (WNV) with a key role in its epidemiology. WNV lineage 1 associated fatal cases of human encephalitis in 2011 and acute flaccid paralysis in 2013 were reported in Alappuzha district, Kerala, India. But no information is available on WNV circulation in domestic ducks, which are abundant, cohabit with humans and occupy wetlands and water bodies in the region. To determine the extent of WNV infection, we investigated 209 sera, 250 oral and 350 cloacal swab samples from local Chara and Chemballi domestic ducks (Anas platyrhynchos var domesticus) in the districts of Alappuzha, Kottayam, Kollam and Pathanamthitta collected during January and March 2015. The serum samples were tested for WNV antibodies first by a competition ELISA and then by a micro virus neutralization test (micro-VNT), while oral and cloacal swabs were subjected to WNV real-time RT-PCR. Ninety five ducks showed evidence of flavivirus antibodies by ELISA. End point neutralizing antibody titre against WNV and Japanese encephalitis virus (JEV) revealed WNV specific antibodies in 24 (11.5%) ducks in 3 districts, JEV specific antibodies in 21 (10%) ducks in 2 districts and flavivirus specific antibodies in 19 (9%) ducks. However, no WNV genomic RNA could be detected. The results of this study demonstrate evidence of widespread WNV and JEV infection in domestic ducks in Kuttanad region, Kerala with a higher seroprevalence to WNV than JEV. Additionally, it highlights the utility of domestic ducks as a surveillance tool to detect WNV/JEV circulation in a region. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Identification and characterization of a virus-specific continuous B-cell epitope on the PrM/M protein of Japanese Encephalitis Virus: potential application in the detection of antibodies to distinguish Japanese Encephalitis Virus infection from West Nile Virus and Dengue Virus infections

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    Liu Wen-Xin

    2010-09-01

    Full Text Available Abstract Background Differential diagnose of Japanese encephalitis virus (JEV infection from other flavivirus especially West Nile virus (WNV and Dengue virus (DV infection was greatly hindered for the serological cross-reactive. Virus specific epitopes could benefit for developing JEV specific antibodies detection methods. To identify the JEV specific epitopes, we fully mapped and characterized the continuous B-cell epitope of the PrM/M protein of JEV. Results To map the epitopes on the PrM/M protein, we designed a set of 20 partially overlapping fragments spanning the whole PrM, fused them with GST, and expressed them in an expression vector. Linear epitope M14 (105VNKKEAWLDSTKATRY120 was detected by enzyme-linked immunosorbent assay (ELISA. By removing amino acid residues individually from the carboxy and amino terminal of peptide M14, we confirmed that the minimal unit of the linear epitope of PrM/M was M14-13 (108KEAWLDSTKAT118. This epitope was highly conserved across different JEV strains. Moreover, this epitope did not cross-react with WNV-positive and DENV-positive sera. Conclusion Epitope M14-13 was a JEV specific lineal B-cell epitpe. The results may provide a useful basis for the development of epitope-based virus specific diagnostic clinical techniques.

  6. Tick-borne encephalitis virus, ticks and humans: short-term and long-term dynamics.

    Science.gov (United States)

    Randolph, Sarah E

    2008-10-01

    Much public health concern and scientific interest has been kindled by significant increases in incidence of tick-borne encephalitis over the past 1-2 decades. It is the most important vector-borne disease of humans in Europe, for which excellent long-term data allow robust quantitative analyses. Despite the increasing tendency to attribute all increases in vector-borne diseases to climate change, there is no convincing evidence that the appearance of new foci in Sweden, Switzerland, France and Germany during this century, or the upsurge in cases within well recognized endemic regions, is due to the recorded minor extensions of infectious ticks into higher altitudes and latitudes and into winter periods, in response to warmer conditions. Rather, there is now good evidence of greater human exposure to infected ticks through altered socioeconomic circumstances (in addition to higher densities of tick-feeding deer--not reviewed here), so far best quantified for Central and Eastern Europe. Increased awareness of tick-borne encephalitis and understanding of the changing risk factors, including the role of human behaviour, will ensure better personal protection against infection, including vaccination and avoidance of high-risk activities.

  7. Pigsties near dwellings as a potential risk factor for the prevalence of Japanese encephalitis virus in adult in Shanxi, China.

    Science.gov (United States)

    Ren, Xiaojie; Fu, Shihong; Dai, Peifang; Wang, Huanyu; Li, Yuanyuan; Li, Xiaolong; Lei, Wenwen; Gao, Xiaoyan; He, Ying; Lv, Zhi; Cheng, Jingxia; Wang, Guiqin; Liang, Guodong

    2017-06-08

    The increasing trend of adult cases of Japanese encephalitis (JE) in China, particularly in northern China, has become an important public health issue. We conducted an epidemiological investigation in the south of Shanxi Province to examine the relationships between mosquitoes, Japanese encephalitis virus (JEV), and adult JE cases. Mosquito specimens were collected from the courtyards of farmers' households and pig farms in Shanxi Province. Mosquitoes were pooled, homogenized, and centrifuged. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect mosquito-borne arbovirus genes in homogenates. Specimens positive for these genes were inoculated into the baby hamster kidney cell line (BHK-21) to isolate virus. Minimum infection rate was calculated and phylogenetic analyses were performed. A total of 7 943 mosquitoes belonging to six species in four genera were collected; Culex tritaeniorhynchus accounted for 73.08% (5 805/7 943), C. pipiens pallens for 24.75% (1 966/7 943), and the remaining 3% (104/ 7943) consisted of Anopheles sinensis, Aedes vexans, Ae. dorsalis, and Armigeres subalbatus. Sixteen pools were positive for JEV based on RT-PCR using JEV pre-membrane gene nested primers. Phylogenetic analyses showed that all JEVs belonged to genotype I; two pools were positive using Getah Virus (GETV) gene primers. In addition, one JEV strain (SXYC1523) was isolated from C. pipiens pallens specimens. These results indicate that the minimum infection rate of JEV in mosquito specimens collected from the courtyards of farmers' households with pigsties was 7.39/1 000; the rate for pig farms was 2.68/1 000; and the rate for farmers' courtyards without pigsties was zero. The high-prevalence regions of adult JE investigated in this study are still the natural epidemic focus of JEV. Having pigsties near dwellings is a potential risk factor contributing to the prevalence of adult JE. To prevent the occurrence of local adult JE cases, a recommendation was

  8. Tissue tropism and molecular characterization of a Japanese encephalitis virus strain isolated from pigs in southwest China.

    Science.gov (United States)

    Yuan, Lei; Wu, Rui; Liu, Hanyang; Wen, Xintian; Huang, Xiaobo; Wen, Yiping; Ma, Xiaoping; Yan, Qigui; Huang, Yong; Zhao, Qin; Cao, Sanjie

    2016-04-02

    Since September 2012, an epidemic has been spreading among swine in a pig farm located in Sichuan province, southwest China, which has resulted in abortion, stillbirth, and fetal mummification. The brains of stillborn pigs were collected and a previously unknown Japanese encephalitis virus (JEV), namely SCYA201201, was isolated. According to the results of agarose gel diffusion precipitation, indirect immunofluorescence analysis, neutralization testing, reverse transcription PCR (RT-PCR) amplification, and physical and chemical testing, the virus was conformed to have the characteristics of JEV. The virus titer in BHK-21 cells was 10(8.47)PFU/ml and the median lethal dose (LD50) to 3-week-old and 7-day-old mice was 1.99 log10 and 1.02 log10 PFU/LD50, respectively. The results of tissue tropism for mice showed that the viral load in the brain was significantly higher than other organs, indicating that the isolate was strongly neurotropic. Additionally, the complete genome sequence of the isolate was determined and compared with other JEV strains. Phylogenetic analysis showed that the isolate belongs to genotype I and may be an imported virus. The isolate had 88.4% nucleotide identity with the Chinese vaccine strain SA14-14-2. However, there were 69 amino acid substitutions compared with the strain SA14-14-2. Some substitutions indicated that SCYA201201 was highly neurovirulent and infective, in accordance with the results of animal testing. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Prevalence of antibodies to Japanese encephalitis virus among inhabitants in Java Island, Indonesia, with a small pig population.

    Science.gov (United States)

    Konishi, Eiji; Sakai, Yohei; Kitai, Yoko; Yamanaka, Atsushi

    2009-05-01

    Japanese encephalitis virus (JEV) is maintained through a transmission cycle between amplifier swine and vector mosquitoes in a peridomestic environment. Thus, studies on natural JEV activities in an environment with a small size of pig population have been limited. Here, we surveyed antibodies against JEV in inhabitants of Jakarta and Surabaya located in Java Island (Indonesia), which has a small swine population. Overall, 2.2% of 1,211 sera collected in Jakarta and 1.8% of 1,751 sera collected in Surabaya had neutralizing antibody titers of >or= 1:160 (90% plaque reduction). All the samples with titers of >or= 1:160 against JEV were also examined for neutralizing antibodies against each of four dengue viruses to confirm that JEV antibody prevalences obtained in the present survey were not attributable to serologic cross-reactivities among flaviviruses distributed in Java. These results indicated that people in Java Island are exposed to natural JEV infections despite a small swine population.

  10. A Review of Methods for Detecting Tick-Borne Encephalitis Virus Infection in Tick, Animal, and Human Specimens.

    Science.gov (United States)

    Ergunay, Koray; Tkachev, Sergey; Kozlova, Irina; Růžek, Daniel

    2016-01-01

    Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted arbovirus causing human disease in Europe and Asia. Over the past decades, the incidence of TBEV infection has significantly increased, with over 13,000 annual hospital referrals in endemic countries and cases emerging in previously unaffected regions. Specific detection of TBEV is required to diagnose suspected human cases or during surveillance of tick vectors and/or susceptible animal species. Widely used techniques for diagnosis comprise serological methods to detect viral antigens or antibodies and nucleic acid tests to detect viral RNA in target specimens. Moreover, virus isolation using susceptible cell lines or vertebrates, electron microscopy, or immunohistochemistry can also be employed on specific occasions. The purpose of this review is to compile and outline various approaches and techniques for detecting TBEV infection in ticks, wild animals, and humans. Specific sections for specimen collection and storage, nucleic acid testing, and serological assays cover various aspects of dynamics, performance characteristics, and utility in the diagnostic workup of suspected cases. Impact of immunoglobulin M testing and quantification, immunoglobulin G avidity, and real-time and quantitative polymerase chain reaction methods were overviewed with assay comparisons. Recent advances in serological assays to mitigate the impact of cross-reactions were further discussed along with the detailed interpretation of laboratory test results in human infections.

  11. Characterization of the GXXXG motif in the first transmembrane segment of Japanese encephalitis virus precursor membrane (prM protein

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    Wu Suh-Chin

    2010-05-01

    Full Text Available Abstract The interaction between prM and E proteins in flavivirus-infected cells is a major driving force for the assembly of flavivirus particles. We used site-directed mutagenesis to study the potential role of the transmembrane domains of the prM proteins of Japanese encephalitis virus (JEV in prM-E heterodimerization as well as subviral particle formation. Alanine insertion scanning mutagenesis within the GXXXG motif in the first transmembrane segment of JEV prM protein affected the prM-E heterodimerization; its specificity was confirmed by replacing the two glycines of the GXXXG motif with alanine, leucine and valine. The GXXXG motif was found to be conserved in the JEV serocomplex viruses but not other flavivirus groups. These mutants with alanine inserted in the two prM transmembrane segments all impaired subviral particle formation in cell cultures. The prM transmembrane domains of JEV may play importation roles in prM-E heterodimerization and viral particle assembly.

  12. Virus-specific regulatory T cells ameliorate encephalitis by repressing effector T cell functions from priming to effector stages.

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    Jingxian Zhao

    2014-08-01

    Full Text Available Several studies have demonstrated the presence of pathogen-specific Foxp3+ CD4 regulatory T cells (Treg in infected animals, but little is known about where and how these cells affect the effector T cell responses and whether they are more suppressive than bulk Treg populations. We recently showed the presence of both epitope M133-specific Tregs (M133 Treg and conventional CD4 T cells (M133 Tconv in the brains of mice with coronavirus-induced encephalitis. Here, we provide new insights into the interactions between pathogenic Tconv and Tregs responding to the same epitope. M133 Tregs inhibited the proliferation but not initial activation of M133 Tconv in draining lymph nodes (DLN. Further, M133 Tregs inhibited migration of M133 Tconv from the DLN. In addition, M133 Tregs diminished microglia activation and decreased the number and function of Tconv in the infected brain. Thus, virus-specific Tregs inhibited pathogenic CD4 T cell responses during priming and effector stages, particularly those recognizing cognate antigen, and decreased mortality and morbidity without affecting virus clearance. These cells are more suppressive than bulk Tregs and provide a targeted approach to ameliorating immunopathological disease in infectious settings.

  13. Development of electrochemical immunosensors based on different serum antibody immobilization methods for detection of Japanese encephalitis virus

    Science.gov (United States)

    Tran, Quang Huy; Hanh Nguyen, Thi Hong; Mai, Anh Tuan; Thuy Nguyen, Thi; Khue Vu, Quang; Nga Phan, Thi

    2012-03-01

    This paper describes the development of electrochemical immunosensors based on human serum antibodies with different immobilization methods for detection of Japanese encephalitis virus (JEV). Human serum containing anti-JEV antibodies was used to immobilize onto the surface of silanized interdigitated electrodes by four methods: direct adsorption (APTES-serum), covalent binding with a cross linker of glutaraldehyde (APTES-GA-serum), covalent binding with a cross linker of glutaraldehyde combined with anti-human IgG (APTES-GA-anti-HIgG-serum) and covalent binding with a cross linker of glutaraldehyde combined with a bioaffinity of protein A (APTES-GA-PrA-serum). Atomic force microscopy was used to verify surface characteristics of the interdigitated electrodes before and after treatment with serum antibodies. The output signal of the immunosensors was measured by the change of conductivity resulting from the specific binding of JEV antigens and serum antibodies immobilized on the electrodes, with the help of horseradish peroxidase (HRP)-labeled secondary antibody against JEV. The results showed that the APTES-GA-PrA-serum method provided the highest signal of the electrochemical immunosensor for detection of JEV antigens, with the linear range from 25 ng ml-1 to 1 μg ml-1, and the limit of detection was about 10 ng ml-1. This study shows a potential development of novel electrochemical immunosensors applied for virus detection in clinical samples in case of possible outbreaks.

  14. Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and anti-tumor effects

    OpenAIRE

    Osada, Takuya; Berglund, Peter; Morse, Michael A.; Hubby, Bolyn; Lewis, Whitney; Niedzwiecki, Donna; Hobeika, Amy; Burnett, Bruce; Devi, Gayathri R.; Clay, Timothy M.; Smith, Jonathan; Lyerly, H. Kim

    2012-01-01

    We recently demonstrated that Venezuelan equine encephalitis (VEE) virus-based replicon particles (VRP) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP expressing Interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and anti-tumor efficacy. Mice were immunized with VRP encoding the human tumor-associat...

  15. Cross-reactivity of human monoclonal antibodies generated with peripheral blood lymphocytes from dengue patients with Japanese encephalitis virus

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    Pipattanaboon C

    2013-08-01

    Full Text Available Chonlatip Pipattanaboon,1,3,8,* Tadahiro Sasaki,2,8,* Mitsuhiro Nishimura,2,8 Chayanee Setthapramote,1,8 Pannamthip Pitaksajjakul,1,4,8 Pornsawan Leaungwutiwong,1,3,8 Kriengsak Limkittikul,5,8 Orapim Puiprom,6 Mikiko Sasayama,6 Panjaporn Chaichana,6 Tamaki Okabayashi,6 Takeshi Kurosu,2,8 Ken-ichiro Ono,7,8 Pongrama Ramasoota,1,4,8 Kazuyoshi Ikuta2,8 1Center of Excellence for Antibody Research, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 2Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; 3Department of Microbiology and Immunology, 4Department of Social and Environmental Medicine, 5Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, 6Mahidol-Osaka Center for Infectious Diseases, Bangkok, Thailand; 7Medical and Biological Laboratories Corporation Ltd, Nagano, Japan; 8JST/JICA, Science and Technology Research Partnership for Sustainable Development, Tokyo, Japan *These authors made an equal contribution to this study Background: Hybridomas that produce human monoclonal antibodies (HuMAbs against Dengue virus (DV had been prepared previously using peripheral blood lymphocytes from patients with DV during the acute and convalescent phases of a secondary infection. Anti-DV envelope glycoprotein (E 99 clones, anti-DV premembrane protein (prM 8 clones, and anti-DV nonstructural protein 1 (NS1 4 clones were derived from four acute-phase patients, and anti-DV E 2 clones, anti-DV prM 2 clones, and anti-DV NS1 8 clones were derived from five convalescent-phase patients. Methods and results: In the present study, we examined whether these clones cross-reacted with Japanese encephalitis virus (JEV, which belongs to the same virus family. Forty-six of the above-described 99 (46/99 anti-E, 0/8 anti-prM, and 2/4 anti-NS1 HuMAbs from acute-phase, and 0/2 anti-E, 0/2 anti-prM, and 5/8 anti-NS1 HuMAbs from convalescent-phase showed neutralizing activity against

  16. Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity

    Science.gov (United States)

    Guo, Yiqi; Audry, Magali; Ciancanelli, Michael; Alsina, Laia; Azevedo, Joana; Herman, Melina; Anguiano, Esperanza; Sancho-Shimizu, Vanessa; Lorenzo, Lazaro; Pauwels, Elodie; Philippe, Paul Bastard; Pérez de Diego, Rebeca; Cardon, Annabelle; Vogt, Guillaume; Picard, Capucine; Andrianirina, Zafitsara Zo; Rozenberg, Flore; Lebon, Pierre; Plancoulaine, Sabine; Tardieu, Marc; Valérie Doireau; Jouanguy, Emmanuelle; Chaussabel, Damien; Geissmann, Frederic; Abel, Laurent

    2011-01-01

    Autosomal dominant TLR3 deficiency has been identified as a genetic etiology of childhood herpes simplex virus 1 (HSV-1) encephalitis (HSE). This defect is partial, as it results in impaired, but not abolished induction of IFN-β and -λ in fibroblasts in response to TLR3 stimulation. The apparently normal resistance of these patients to other infections, viral illnesses in particular, may thus result from residual TLR3 responses. We report here an autosomal recessive form of complete TLR3 deficiency in a young man who developed HSE in childhood but remained normally resistant to other infections. This patient is compound heterozygous for two loss-of-function TLR3 alleles, resulting in an absence of response to TLR3 activation by polyinosinic-polycytidylic acid (poly(I:C)) and related agonists in his fibroblasts. Moreover, upon infection of the patient’s fibroblasts with HSV-1, the impairment of IFN-β and -λ production resulted in high levels of viral replication and cell death. In contrast, the patient’s peripheral blood mononuclear cells responded normally to poly(I:C) and to all viruses tested, including HSV-1. Consistently, various TLR3-deficient leukocytes from the patient, including CD14+ and/or CD16+ monocytes, plasmacytoid dendritic cells, and in vitro derived monocyte-derived macrophages, responded normally to both poly(I:C) and HSV-1, with the induction of antiviral IFN production. These findings identify a new genetic etiology for childhood HSE, indicating that TLR3-mediated immunity is essential for protective immunity to HSV-1 in the central nervous system (CNS) during primary infection in childhood, in at least some patients. They also indicate that human TLR3 is largely redundant for responses to double-stranded RNA and HSV-1 in various leukocytes, probably accounting for the redundancy of TLR3 for host defense against viruses, including HSV-1, outside the CNS. PMID:21911422

  17. Southernmost Asia Is the Source of Japanese Encephalitis Virus (Genotype 1) Diversity from which the Viruses Disperse and Evolve throughout Asia

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    Wang, Huanyu; Fu, Shihong; Guo, Zhenyang; Liang, Guodong

    2013-01-01

    Background Although a previous study predicted that Japanese encephalitis virus (JEV) originated in the Malaysia/Indonesia region, the virus is known to circulate mainly on the Asian continent. However, there are no reported systematic studies that adequately define how JEV then dispersed throughout Asia. Methodology/Principal Findings In order to understand the mode of JEV dispersal throughout the entire Asian continent and the factors that determine the dispersal characteristics of JEV, a phylogenetic analysis using Bayesian Markov chain Monte Carlo simulations was conducted on all available JEV E gene sequences in GenBank, plus strains recently isolated in China. Here we demonstrate for the first time that JEV lineages can be divided into four endemic cycles, comprising southern Asia, eastern coastal Asia, western Asia, and central Asia. The isolation places of the viruses in each endemic cycle were geographically independent regardless of years, vectors, and hosts of isolation. Following further analysis, we propose that the southernmost region (Thailand, Vietnam, and Yunnan Province, China) was the source of JEV transmission to the Asian continent following its emergence. Three independent transmission routes from the south to north appear to define subsequent dispersal of JEV. Analysis of JEV population dynamics further supports these concepts. Conclusions/Significance These results and their interpretation provide new insights into our understanding of JEV evolution and dispersal and highlight its potential for introduction into non-endemic areas. PMID:24069502

  18. Tick-borne encephalitis.

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    Lindquist, Lars; Vapalahti, Olli

    2008-05-31

    We review the epidemiological and clinical characteristics of tick-borne encephalitis, and summarise biological and virological aspects that are important for understanding the life-cycle and transmission of the virus. Tick-borne encephalitis virus is a flavivirus that is transmitted by Ixodes spp ticks in a vast area from western Europe to the eastern coast of Japan. Tick-borne encephalitis causes acute meningoencephalitis with or without myelitis. Morbidity is age dependent, and is highest in adults of whom half develop encephalitis. A third of patients have longlasting sequelae, frequently with cognitive dysfunction and substantial impairment in quality of life. The disease arises in patchy endemic foci in Europe, with climatic and ecological conditions suitable for circulation of the virus. Climate change and leisure habits expose more people to tick-bites and have contributed to the increase in number of cases despite availability of effective vaccines. The serological diagnosis is usually straightforward. No specific treatment for the disease exists, and immunisation is the main preventive measure.

  19. The occurrence of Ixodes ricinus ticks and important tick-borne pathogens in areas with high tick-borne encephalitis prevalence in different altitudinal levels of the Czech Republic Part I. Ixodes ricinus ticks and tick-borne encephalitis virus.

    Science.gov (United States)

    Daniel, M; Danielová, V; Kříž, B; Růžek, D; Fialová, A; Malý, M; Materna, J; Pejčoch, M; Erhart, J

    The aim of the three-year study (2011-2013) was to monitor population density of Ixodes ricinus ticks and its infection rate with the tick-borne encephalitis virus in areas with a high incidence of tick-borne encephalitis as reported in the previous decade 2001-2010. Such a comprehensive and long-term study based on existing epidemiolo-gical findings has not previously been conducted in Europe. In the areas of the Ústí nad Labem Region, Olomouc Region, South Bohemian Region, and Highlands Region, 600 m2 plots were selected in the local optimal I. ricinus habitats where tick flagging was performed every year in the spring-summer and autumn seasons of the questing activity. In total, 18,721 I. ricinus ticks (1448 females, 1425 males, and 15,848 nymphs) were collected and investigated. The results have shown that the differences in the infection rate of I. ricinus observed between regions are driven by variation in the density of the local I. ricinus populations which is influenced by the characteris-tics of the whole local biocenosis. The overall prevalence estimate of TBE virus in Ixodes ricinus ticks at the altitudes below 600 m a.s.l. was 0.096 % (95% CI 0.055-0.156) for nymphs, and 0.477 % (95% CI 0.272-0.773) for adults. The dynamics of the seasonal variation in I. ricinus populations, depending primarily on the climatic factors, are behind the interyear differences in the infection rate of ticks and, consequently, in the epidemiological situation of tick-borne encephalitis. The nymph to adult ratio was 5.5 on average but showed great interregional variability (from 10.3 in the Ústí nad Labem Region to 1.8 in the Highlands Region). It might be used in the future as one of the indicators of the composition of the local I. ricinus population and of the level of the circulation of tick-borne pathogens in zoonotic sphere and also for use in the health risk assessment in a given area. Despite the permanent expansion of ticks and tick-borne pathogens in higher

  20. Vector-Host Interactions of Culiseta melanura in a Focus of Eastern Equine Encephalitis Virus Activity in Southeastern Virginia.

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    Goudarz Molaei

    Full Text Available Eastern equine encephalitis virus (EEEV causes a highly pathogenic mosquito-borne zoonosis that is responsible for sporadic outbreaks of severe illness in humans and equines in the eastern USA. Culiseta (Cs. melanura is the primary vector of EEEV in most geographic regions but its feeding patterns on specific avian and mammalian hosts are largely unknown in the mid-Atlantic region. The objectives of our study were to: 1 identify avian hosts of Cs. melanura and evaluate their potential role in enzootic amplification of EEEV, 2 assess spatial and temporal patterns of virus activity during a season of intense virus transmission, and 3 investigate the potential role of Cs. melanura in epidemic/epizootic transmission of EEEV to humans and equines. Accordingly, we collected mosquitoes at 55 sites in Suffolk, Virginia in 2013, and identified the source of blood meals in engorged mosquitoes by nucleotide sequencing PCR products of the mitochondrial cytochrome b gene. We also examined field-collected mosquitoes for evidence of infection with EEEV using Vector Test, cell culture, and PCR. Analysis of 188 engorged Cs. melanura sampled from April through October 2013 indicated that 95.2%, 4.3%, and 0.5% obtained blood meals from avian, mammalian, and reptilian hosts, respectively. American Robin was the most frequently identified host for Cs. melanura (42.6% of blood meals followed by Northern Cardinal (16.0%, European Starling (11.2%, Carolina Wren (4.3%, and Common Grackle (4.3%. EEEV was detected in 106 mosquito pools of Cs. melanura, and the number of virus positive pools peaked in late July with 22 positive pools and a Maximum Likelihood Estimation (MLE infection rate of 4.46 per 1,000 mosquitoes. Our findings highlight the importance of Cs. melanura as a regional EEEV vector based on frequent feeding on virus-competent bird species. A small proportion of blood meals acquired from mammalian hosts suggests the possibility that this species may

  1. N-methylisatin-beta-thiosemicarbazone derivative (SCH 16) is an inhibitor of Japanese encephalitis virus infection in vitro and in vivo

    Science.gov (United States)

    Sebastian, Liba; Desai, Anita; Shampur, Madhusudana N; Perumal, Yogeeswari; Sriram, D; Vasanthapuram, Ravi

    2008-01-01

    Background During the early and mid part of 20th century, several reports described the therapeutic effects of N-methylisatin-β-Thiosemicarbazone (MIBT) against pox viruses, Maloney leukemia viruses and recently against HIV. However, their ability to inhibit flavivirus replication has not been investigated. Hence the present study was designed to evaluate the antiviral activity of 14 MIBT derivatives against Flaviviruses that are prevalent in India such as Japanese Encephalitis Virus (JEV), Dengue-2 (Den-2) and West Nile viruses (WNV). Results Amongst the fourteen Mannich bases of MIBT derivatives tested one compound – SCH 16 was able to completely inhibit in vitro Japanese encephalitis virus (JEV) and West Nile virus (WNV) replication. However no antiviral activity of SCH 16 was noted against Den-2 virus replication. This compound was able to inhibit 50% of the plaques (IC50) produced by JEV and WNV at a concentration of 16 μgm/ml (0.000025 μM) and 4 μgm/ml (0.000006 μM) respectively. Furthermore, SCH 16 at a concentration of 500 mg/kg body weight administered by oral route twice daily was able to completely (100%) prevent mortality in mice challenged with 50LD50 JEV by the peripheral route. Our experiments to understand the mechanism of action suggest that SCH 16 inhibited JEV replication at the level of early protein translation. Conclusion Only one of the 14 isatin derivatives -SCH 16 exhibited antiviral action on JEV and WNV virus infection in vitro. SCH 16 was also found to completely inhibit JEV replication in vivo in a mouse model challenged peripherally with 50LD50 of the virus. These results warrant further research and development on SCH 16 as a possible therapeutic agent. PMID:18498627

  2. N-methylisatin-beta-thiosemicarbazone derivative (SCH 16 is an inhibitor of Japanese encephalitis virus infection in vitro and in vivo

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    Sriram D

    2008-05-01

    Full Text Available Abstract Background During the early and mid part of 20th century, several reports described the therapeutic effects of N-methylisatin-β-Thiosemicarbazone (MIBT against pox viruses, Maloney leukemia viruses and recently against HIV. However, their ability to inhibit flavivirus replication has not been investigated. Hence the present study was designed to evaluate the antiviral activity of 14 MIBT derivatives against Flaviviruses that are prevalent in India such as Japanese Encephalitis Virus (JEV, Dengue-2 (Den-2 and West Nile viruses (WNV. Results Amongst the fourteen Mannich bases of MIBT derivatives tested one compound – SCH 16 was able to completely inhibit in vitro Japanese encephalitis virus (JEV and West Nile virus (WNV replication. However no antiviral activity of SCH 16 was noted against Den-2 virus replication. This compound was able to inhibit 50% of the plaques (IC50 produced by JEV and WNV at a concentration of 16 μgm/ml (0.000025 μM and 4 μgm/ml (0.000006 μM respectively. Furthermore, SCH 16 at a concentration of 500 mg/kg body weight administered by oral route twice daily was able to completely (100% prevent mortality in mice challenged with 50LD50 JEV by the peripheral route. Our experiments to understand the mechanism of action suggest that SCH 16 inhibited JEV replication at the level of early protein translation. Conclusion Only one of the 14 isatin derivatives -SCH 16 exhibited antiviral action on JEV and WNV virus infection in vitro. SCH 16 was also found to completely inhibit JEV replication in vivo in a mouse model challenged peripherally with 50LD50 of the virus. These results warrant further research and development on SCH 16 as a possible therapeutic agent.

  3. Herpes-simplex virus encephalitis is characterized by an early MMP-9 increase and collagen type IV degradation.

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    Sellner, Johann; Simon, Franziska; Meyding-Lamade, Uta; Leib, Stephen L

    2006-12-13

    Cerebrovascular complications including cerebral edema, raised intracranial pressure and hemorrhage contribute to the high mortality and morbidity of herpes-simplex virus encephalitis (HSE). We examined changes of collagen type IV, the major constituent of the neurovascular matrix, together with expression and localization of matrix-degrading enzymes during the development of acute HSE. In an experimental model of focal HSE, we found that early, symptomatic HSE (3 days after infection) and acute, fully developed HSE (7 days after infection) are associated with significantly raised levels of matrix-metalloproteinase-9 (MMP-9) (both PHSE and further expanded towards the perivascular space and adjacent tissue in acute HSE. Around the cerebral vasculature, we observed that MMP-9 activity was insufficiently counterbalanced by its endogenous tissue inhibitor of MMP (TIMP) TIMP-1, resulting in loss of collagen type IV. Our findings suggest that MMP-9 is involved in the evolution of HSE by causing damage to the cerebral vasculature. The degradation of the neurovascular matrix in HSE facilitates the development of cerebrovascular complications and may represent a target for novel adjuvant treatment strategies.

  4. Sustained Elevation of Kynurenic Acid in the Cerebrospinal Fluid of Patients with Herpes Simplex Virus Type 1 Encephalitis

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    Ann Atlas

    2013-01-01

    Full Text Available Herpes simplex virus (HSV type 1 encephalitis (HSE is a viral infectious disease with commonly occurring neurodegeneration and neurological/cognitive long-term sequelae. Kynurenic acid (KYNA is a neuroactive tryptophan metabolite, which is elevated in the cerebrospinal fluid (CSF during viral infection as a result of immune activation. The aim of the study was to investigate the role of endogenous brain KYNA for the long-term outcome of the disease. CSF KYNA concentration was analyzed in 25 HSE patients along the course of the disease and compared with that of 25 age-matched healthy volunteers. Within 3 weeks of admission CSF KYNA of HSE patients was markedly elevated (median 33.6 nM compared to healthy volunteers (median 1.45 nM. Following a decline observed after 1–2 months, levels of CSF KYNA were elevated more than 1 year after admission (median 3.4 nM range: 1–9 years. A negative correlation was found between initial CSF KYNA concentrations and severity of the long-term sequelae. This study show a marked elevation in CSF KYNA from patients with HSE, most pronounced during the acute phase of the disease and slowly declining along the recovery. We propose that brain KYNA might potentially protect against neurodegeneration while causing a long-lasting loss in cognitive function associated with the disease.

  5. Characterizing areas of potential human exposure to eastern equine encephalitis virus using serological and clinical data from horses.

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    Rocheleau, J-P; Arsenault, J; Ogden, N H; Lindsay, L R; Drebot, M; Michel, P

    2017-03-01

    Eastern equine encephalitis (EEE) is a rare but severe emerging vector-borne disease affecting human and animal populations in the northeastern United States where it is endemic. Key knowledge gaps remain about the epidemiology of EEE virus (EEEV) in areas where its emergence has more recently been reported. In Eastern Canada, viral activity has been recorded in mosquitoes and horses throughout the 2000s but cases of EEEV in humans have not been reported so far. This study was designed to provide an assessment of possible EEEV human exposure by modelling environmental risk factors for EEEV in horses, identifying high-risk environments and mapping risk in the province of Quebec, Canada. According to logistic models, being located near wooded swamps was a risk factor for seropositivity or disease in horses [odds ratio (OR) 4·15, 95% confidence interval (CI) 1·16-14·8) whereas being located on agricultural lands was identified as protective (OR 0·75, 95% CI 0·62-0·92). A better understanding of the environmental risk of exposure to EEEV in Canada provides veterinary and public health officials with enhanced means to more effectively monitor the emergence of this public health risk and design targeted surveillance and preventive measures.

  6. Blood and milk polymorphonuclear leukocyte and monocyte/macrophage functions in naturally caprine arthritis encephalitis virus infection in dairy goats.

    Science.gov (United States)

    Santos, Bruna Parapinski; Souza, Fernando Nogueira; Blagitz, Maiara Garcia; Batista, Camila Freitas; Bertagnon, Heloísa Godoi; Diniz, Soraia Araújo; Silva, Marcos Xavier; Haddad, João Paulo Amaral; Della Libera, Alice Maria Melville Paiva

    2017-06-01

    The exact influence of caprine arthritis encephalitis virus (CAEV) infection on blood and milk polymorphonuclear leukocytes (PMNLs) and monocyte/macrophages of goats remains unclear. Thus, the present study sought to explore the blood and milk PMNL and monocyte/macrophage functions in naturally CAEV-infected goats. The present study used 18 healthy Saanen goats that were segregated according to sera test outcomes into serologically CAEV negative (n=8; 14 halves) and positive (n=10; 14 halves) groups. All milk samples from mammary halves with milk bacteriologically positive outcomes, somatic cell count ≥2×106cellsmL-1, and abnormal secretions in the strip cup test were excluded. We evaluated the percentage of blood and milk PMNLs and monocyte/macrophages, the viability of PMNLs and monocyte/macrophages, the levels of intracellular reactive oxygen species (ROS) and the nonopsonized phagocytosis of Staphylococcus aureus and Escherichia coli by flow cytometry. In the present study, a higher percentage of milk macrophages (CD14+) and milk polymorphonuclear leukocytes undergoing late apoptosis or necrosis (Annexin-V+/Propidium iodide+) was observed in CAEV-infected goats; we did not find any further alterations in blood and milk PMNL and monocyte/macrophage functions. Thus, regarding our results, the goats naturally infected with CAEV did not reveal pronounced dysfunctions in blood and milk polymorphonuclear leukocytes and monocytes/macrophages. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Characterization of immune responses induced by inactivated, live attenuated and DNA vaccines against Japanese encephalitis virus in mice.

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    Li, Jieqiong; Chen, Hui; Wu, Na; Fan, Dongying; Liang, Guodong; Gao, Na; An, Jing

    2013-08-28

    Vaccination is the most effective countermeasure for protecting individuals from Japanese encephalitis virus (JEV) infection. There are two types of JEV vaccines currently used in China: the Vero cell-derived inactivated vaccine and the live attenuated vaccine. In this study, we characterized the immune response and protective efficacy induced in mice by the inactivated vaccine, live attenuated vaccine and the DNA vaccine candidate pCAG-JME, which expresses JEV prM-E proteins. We found that the live attenuated vaccine conferred 100% protection and resulted in the generation of high levels of specific anti-JEV antibodies and cytokines. The pCAG-JME vaccine induced protective immunity as well as the live attenuated vaccine. Unexpectedly, immunization with the inactivated vaccine only induced a limited immune response and partial protection, which may be due to the decreased activity of dendritic cells and the expansion of CD4+CD25+Foxp3+ regulatory T cells observed in these mice. Altogether, our results suggest that the live attenuated vaccine is more effective in providing protection against JEV infection than the inactivated vaccine and that pCAG-JME will be a potential JEV vaccine candidate. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Zika Virus-Associated Neurological Disease in the Adult: Guillain-Barré Syndrome, Encephalitis, and Myelitis.

    Science.gov (United States)

    Muñoz, Laura S; Barreras, Paula; Pardo, Carlos A

    2016-09-01

    Zika virus (ZIKV) has caused a major infection outbreak in the Americas since 2015. In parallel with the ZIKV epidemic, an increase in cases of neurological disorders which include Guillain-Barré syndrome (GBS), encephalitis, and myelitis have been linked to the infection. We reviewed the evidence suggesting a relationship between ZIKV and neurological disorders in adults. A search of the literature supporting such link included databases such as PubMed and the World Health Organization (WHO) surveillance system. Through June 1, 2016, 761 publications were available on PubMed using the search word "Zika." Among those publications as well as surveillance reports released by the WHO and other health organizations, 20 articles linked ZIKV with neurological complications other than microcephaly. They corresponded to population and surveillance studies (n = 7), case reports (n = 9), case series (n = 3), and case-control studies (n = 1). Articles were also included if they provided information related to possible mechanisms of ZIKV neuropathogenesis. Evidence based on epidemiological and virological information supports the hypothesis that ZIKV infection is associated with GBS. Although cases of encephalopathy and myelitis have also been linked to ZIKV infection, the evidence is scarce and there is a need for virological, epidemiological, and controlled studies to better characterize such relationship. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. Oral immunization of mice with Japanese encephalitis virus envelope protein synthesized in Escherichia coli induces anti-viral antibodies.

    Science.gov (United States)

    Rauthan, Manish; Kaur, Rupinderjeet; Appaiahgari, Mohan Babu; Vrati, Sudhanshu

    2004-11-01

    In order to evaluate the possibility of developing an oral vaccine against Japanese encephalitis virus (JEV), mice were fed with recombinant JEV envelope (E) protein synthesized in Escherichia coli. The protein was administered orally to mice with or without an immunostimulatory cytosine-phosphate-guanosine (CpG) motif containing synthetic oligodeoxynucleotide (ODN) as an adjuvant. The immunized mice made high-titered anti-E and anti-JEV antibodies. Mice immunized with JEV E protein along with the ODN adjuvant produced higher antibody titers and these were predominantly IgG2a type. These antibodies, however, failed to neutralize JEV activity in vitro, and the immunization did not protect the mice against lethal JEV challenge. Splenocytes from the immunized mice secreted large amounts of interferon (IFN)-gamma and showed proliferation in the presence of JEV E protein. Our results indicate that JEV E protein delivered orally to mice together with ODN generated both humoral and cellular immune responses to JEV, and these were of the Th1 type.

  10. Babesia canis and tick-borne encephalitis virus (TBEV) co-infection in a sled dog.

    Science.gov (United States)

    Bajer, Anna; Rodo, Anna; Bednarska, Malgorzata; Mierzejewska, Ewa; Welc-Falęciak, Renata

    2013-01-01

    Sporting dogs, including sled dogs, are particularly prone to tick-borne infection either due to training/racing in forest areas or through visits to endemic areas. The aim was to present tick-borne infections in a 6-dog racing team after a race in Estonia. On the 4th day after return to Poland, the first dog presented with babesiosis symptoms and was diagnosed and treated accordingly. Next morning, the dog showed neurological symptoms and was diagnosed with tick-borne encephalitis (TBE). Diagnosis was confirmed by a high level of IgG antibodies (922 IU/ml), detected in serum 3 months later. The second dog presented with babesiosis symptoms on the 7th day after return. Babesia DNA was extracted from blood, amplified and sequenced to answer the question of whether the dogs became infected during the race in Estonia or in Poland. Sequencing of a fragment of Babesia 18S rDNA revealed that these two isolates were identical to one another and closely related to the B. canis sequence originally isolated from the dog and Dermacentor reticulatus ticks in Poland. Thus, this is the first confirmed case of B.canis and TBEV co-infection and first confirmed case of TBE in a dog in Poland.

  11. Fine mapping of a linear epitope on EDIII of Japanese encephalitis virus using a novel neutralizing monoclonal antibody.

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    Deng, Wen-Lei; Guan, Chi-Yu; Liu, Ke; Zhang, Xiao-Min; Feng, Xiu-Li; Zhou, Bin; Su, Xiao-Dong; Chen, Pu-Yan

    2014-01-22

    The domain III (EDIII) of the envelope protein of Japanese encephalitis virus (JEV) is proposed to play an essential role in JEV replication and infection; it is involved in binding to host receptors and contains specific epitopes that elicit neutralizing antibodies. However, most previous studies have not provided detailed molecular information about the functional epitopes on JEV EDIII protein. In this study, we described a monoclonal antibody (mAb 2B4) we produced and characterized by IFA, PRNT, ELISA and Western blot analyses. The results showed that mAb 2B4 was specific to JEV EDIII protein and possessed high neutralization activity against JEV in vitro. Furthermore, we found that the motif, (394)HHWH(397), was the minimal unit of the linear epitope recognized by mAb 2B4 through screening a phage-displayed random 12-mer peptide library. Using sequence alignment analysis it was found that this motif was highly conserved among JEV strains and was present in West Nile Virus (WNV). Indeed, ELISA data showed that this epitope could be recognized by both JEV-positive swine serum and WNV-positive swine serum. Notably, this linear epitope was highly hydrophilic and was located within the terminal end of a β-pleated sheet of EDIII. An analysis of the spatial conformation supported the possibility of inducing specific antibodies to this epitope. Taken together, we identified (394)HHWH(397) as an EDIII-specific linear epitope recognized by mAb 2B4, which would be beneficial for studying the pathogenic mechanism of JEV; and mAb 2B4 was also a potential diagnostic and therapeutic reagent. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Expression of particulate-form of Japanese encephalitis virus envelope protein in a stably transfected Drosophila cell line

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    Zhang Li

    2007-02-01

    Full Text Available Abstract Background Japanese encephalitis virus (JEV, a member of the family Flaviviridae, is an important mosquito-borne human pathogen. Its envelope glycoprotein (E is the major determinant of the pathogenicity and host immune responses. In the present study, we explored the feasibility of producing recombinant JEV E protein in the virus-free Drosophila expression system. Results The coding sequence for the signal sequence of premembrane and E protein was cloned into the Drosophila expression vector pAc5.1/V5-His. A Drosophila cell line S2 was cotransfected with this construct as well as a plasmid providing hygromycin B resistance. A cell line expressing the JEV E protein was selected by immunofluoresence, confocal microscopy, and western blot analysis using three different monoclonal antibodies directed against JEV E protein. This cell line was stable in the yield of JEV E protein during two months in vitro maintenance in the presence of hygromycin B. The results showed that the recombinant E protein had an expected molecular weight of about 50 kilodalton, was immunoreactive with all three monoclonal antibodies, and found in both the cytoplasm and culture supernatant. Sucrose gradient ultracentrifugation analysis revealed that the secreted E protein product was in a particulate form. It migrated to the sucrose fraction with a density of 1.13 g/ml. Balb/c mice immunised with the sucrose fraction containing the E protein particles developed specific antibodies. These data show that functioning JEV E protein was expressed in the stable S2 cell line. Conclusion The Drosophila expression system is a more convenient, cheaper and safer approach to the production of vaccine candidates and diagnostic reagents for JEV.

  13. Prevalence of Neutralizing Antibodies to Japanese Encephalitis Virus among High-Risk Age Groups in South Korea, 2010

    Science.gov (United States)

    Ju, Young Ran; Han, Myung Guk; Lee, Won-Ja; Jeong, Young Eui

    2016-01-01

    After an extensive vaccination policy, Japanese encephalitis (JE) was nearly eliminated since the mid-1980s in South Korea. Vaccination in children shifted the affected age of JE patients from children to adults. However, an abrupt increase in JE cases occurred in 2010, and this trend has continued. The present study aimed to investigate the prevalence of neutralizing antibodies to the JE virus (JEV) among high-risk age groups (≥40 years) in South Korea. A plaque reduction neutralization test was conducted to evaluate the prevalence of neutralizing antibodies to JEV in 945 subjects within four age groups (30–39, 40–49, 50–59, and 60–69 years) in 10 provinces. Of the 945 enrolled subjects, 927 (98.1%) exhibited antibodies against JEV. No significant differences were found in the prevalence of neutralizing antibodies according to sex, age, or occupation. However, there were significant differences in the plaque reduction rate according to age and occupation; oldest age group had a higher reduction rate, and subjects who were employed in agriculture or forestry also had a higher value than the other occupations. We also found that three provinces (Gangwon, Jeonnam, and Gyeongnam) had a relatively lower plaque reduction rate than the other locations. In addition, enzyme-linked immunosorbent assays were conducted to determine recent viral infections and 12 (2.2%) subjects were found to have been recently infected by the virus. In conclusion, the present study clearly indicated that the prevalence of neutralizing antibodies has been maintained at very high levels among adult age groups owing to vaccination or natural infections, or both. In the future, serosurveillance should be conducted periodically using more representative samples to better understand the population-level immunity to JE in South Korea. PMID:26807709

  14. Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease.

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    Wu, Xiao-Xin; Yao, Hang-Ping; Wu, Nan-Ping; Gao, Hai-Nv; Wu, Hai-Bo; Jin, Chang-Zhong; Lu, Xiang-Yun; Xie, Tian-Shen; Li, Lan-Juan

    2015-01-01

    Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirusx2206;VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD. © 2015 The Author(s) Published by S. Karger AG, Basel.

  15. Guillain-Barré Syndrome, Acute Disseminated Encephalomyelitis and Encephalitis Associated with Zika Virus Infection in Brazil: Detection of Viral RNA and Isolation of Virus during Late Infection.

    Science.gov (United States)

    Brito Ferreira, Maria Lucia; Antunes de Brito, Carlos Alexandre; Moreira, Álvaro José Porto; de Morais Machado, Maria Íris; Henriques-Souza, Adélia; Cordeiro, Marli Tenório; de Azevedo Marques, Ernesto Torres; Pena, Lindomar José

    2017-11-01

    Zika virus (ZIKV) emerged in Brazil in 2015, which was followed by an increase of Guillain-Barre Syndrome (GBS) cases. We report the epidemiological, clinical, and laboratory findings of the first six neurological cases associated with ZIKV in Brazil seen in a reference neurology hospital in Pernambuco, Brazil. In all cases, ZIKV was detected in serum and/or cerebrospinal fluid (CSF) samples. In this case series, four cases were defined as GBS, one as acute disseminated encephalomyelitis (ADEM) and the other as encephalitis. ZIKV was detected in all cases by RT-PCR and virus isolation was successful in two patients. The time between ZIKV acute symptoms and the development of neurological manifestations varied from 3 to 13 days and ZIKV was detected between 15 and 34 days after the initial symptoms. Our results highlight the need to include ZIKV as a differential diagnosis for neurological syndromes in countries with circulation of this arbovirus. Because the viremia in these patients appears to persist longer, direct diagnostic techniques such as RT-PCR and viral isolation should be considered even if it is after the acute phase of viral infection.

  16. Arbovirus investigations in Argentina, 1977-1980. III. Identification and characterization of viruses isolated, including new subtypes of western and Venezuelan equine encephalitis viruses and four new bunyaviruses (Las Maloyas, Resistencia, Barranqueras, and Antequera).

    Science.gov (United States)

    Calisher, C H; Monath, T P; Mitchell, C J; Sabattini, M S; Cropp, C B; Kerschner, J; Hunt, A R; Lazuick, J S

    1985-09-01

    Forty viruses isolated from mosquitoes between 1977 and 1980 in Argentina have been identified and characterized. Nineteen strains of VEE virus, identical by neutralization (N) tests, were shown by hemagglutination-inhibition tests with anti-E2 glycoprotein sera to represent a new subtype VI of the VEE complex. RNA oligonucleotide fingerprints of this virus were distinct from subtype I viruses. The virus was not lethal for English short-haired guinea pigs, indicating that it is probably not equine-virulent. Three strains of a member of the WEE virus complex were shown to differ by N tests in 1 direction from prototype WEE virus. The new WEE subtype was also found to be distinct by RNA oligonucleotide mapping. Its vector relationships indicate that it is an enzootic virus, and it has not been associated with equine disease. A new member of the Anopheles A serogroup was identified, shown to be most closely related to Lukuni and Col An 57389 viruses, and given the name Las Maloyas virus. A strain of Para virus (Bunyaviridae, Bunyavirus) was identified. Six isolates, representing 3 new viruses morphologically resembling bunyaviruses are described; the names Antequera, Barranqueras, and Resistencia are proposed for these agents, which were all isolated from Culex (Melanoconion) delpontei in Chaco Province. No serologic relationships between these viruses and other bunyaviruses were found. Since they are antigenically interrelated, they form a new (Antequera) serogroup. Eight Gamboa serogroup viruses and 2 strains of St. Louis encephalitis virus were also identified.

  17. [Japanese encephalitis in Southern Europe].

    Science.gov (United States)

    Cleton, Natalie; Koopmans, Marion; Braks, Marieta; Van Maanen, Kees; Reusken, Chantal

    2014-07-01

    In 2012, a fragment of the Japanese encephalitis virus (JEV) genome was isolated from a pool of Culex pipiens mosquitoes caught in 2010 and 2011 in Northern Italy. JEV has a broad geographical distribution in South and Southeast Asia and Oceania, and is the most important cause of viral encephalitis in Asia in humans and also causes encephalitis in horses and fertility problems in pigs. However, recently isolated JEV genome fragments in mosquitoes in Italy could be an indication of repeated introduction of JEV, enzootic circulation of JEV or a related virus in Southern Europe. Until more information is available, Japanese encephalitis remains a travel-related infectious disease for travellers to JEV endemic and epidemic areas outside of Europe.

  18. Genetic Determinants of Japanese Encephalitis Virus Vaccine Strain SA14-14-2 That Govern Attenuation of Virulence in Mice.

    Science.gov (United States)

    Gromowski, Gregory D; Firestone, Cai-Yen; Whitehead, Stephen S

    2015-06-01

    The safety and efficacy of the live-attenuated Japanese encephalitis virus (JEV) SA14-14-2 vaccine are attributed to mutations that accumulated in the viral genome during its derivation. However, little is known about the contribution that is made by most of these mutations to virulence attenuation and vaccine immunogenicity. Here, we generated recombinant JEV (rJEV) strains containing JEV SA14-14-2 vaccine-specific mutations that are located in the untranslated regions (UTRs) and seven protein genes or are introduced from PCR-amplified regions of the JEV SA14-14-2 genome. The resulting mutant viruses were evaluated in tissue culture and in mice. The authentic JEV SA14-14-2 (E) protein, with amino acid substitutions L107F, E138K, I176V, T177A, E244G, Q264H, K279M, A315V, S366A, and K439R relative to the wild-type rJEV clone, was essential and sufficient for complete attenuation of neurovirulence. Individually, the nucleotide substitution T39A in the 5' UTR (5'-UTR-T39A), the capsid (C) protein amino acid substitution L66S (C-L66S), and the complete NS1/2A genome region containing 10 mutations each significantly reduced virus neuroinvasion but not neurovirulence. The levels of peripheral virulence attenuation imposed by the 5'-UTR-T39A and C-L66S mutations, individually, were somewhat mitigated in combination with other vaccine strain-specific mutations, which might be compensatory, and together did not affect immunogenicity. However, a marked reduction in immunogenicity was observed with the addition of the NS1/2A and NS5 vaccine virus genome regions. These results suggest that a second-generation recombinant vaccine can be rationally engineered to maximize levels of immunogenicity without compromising safety. The live-attenuated JEV SA14-14-2 vaccine has been vital for controlling the incidence of disease caused by JEV, particularly in rural areas of Asia where it is endemic. The vaccine was developed >25 years ago by passaging wild-type JEV strain SA14 in tissue

  19. Detection Of Caprine Arthritis Encephalitis Virus Gag-Gene By Rt ...

    African Journals Online (AJOL)

    Predominantly, cells of the monocyte-macrophage lineage were specifically infected by the virus as proviral DNA was detected in infected cultures by amplification of a 414 base-pair (bp) fragment of the viral gag-gene by Reverse Transcription- Polymerase Chain Reaction (RT-PCR) technique. The present study revealed ...

  20. Virion polypeptide heterogeneity among virulent and avirulent strains of eastern equine encephalitis (EEE) virus.

    Science.gov (United States)

    Walder, R; Rosato, R R; Eddy, G A

    1981-01-01

    Comparative analysis of structural virion polypeptides of 24 selected EEE virus strains, representing North and South American types, was performed by one-dimensional discontinuous sodium dodecyl sulfate (SDS)-polyacrylamide-gel electrophoresis (PAGE). The structural proteins of different EEE virus isolates, resolved by this method, exhibited mol.wts. values in the range of 57-60 X 10(3) for (E-1), 51-54 X 10(3) for (E-2) and 35-38 X 10(3) daltons for the core (NP) nucleocapsid. The exception was the South American human lethal virus, TRVL-89287 strain, which was shown to possess only a single envelope glycoprotein. The high molecular weight envelope (E-1) glycoprotein species was absent or co-migrated adjacent to the smaller envelope (E-2) glycoprotein. Results indicated similarities in the core (NP) proteins, however greater variability in the envelope (E-/ and/or E-2) glycoproteins. Based on these variations seven distinct profiles could be observed among the EEE virus strain studied. The classification based on the patterns of structural polypeptides obtained by SDS-PAGE of these strains does not correlate well with any other previously reported in vitro characteristics (antigenic subtypes, HTP elution profiles) nor with the in vivo virulence markers.

  1. Electron Tomography Analysis of Tick-Borne Encephalitis Virus Infection in Human Neurons

    Czech Academy of Sciences Publication Activity Database

    Bílý, Tomáš; Palus, Martin; Eyer, L.; Elsterová, Jana; Vancová, Marie; Růžek, Daniel

    2015-01-01

    Roč. 5, JUN 15 2015 (2015), s. 10745 ISSN 2045-2322 R&D Projects: GA ČR GAP502/11/2116; GA TA ČR(CZ) TE01020118 Institutional support: RVO:60077344 Keywords : dengue virus * replication sites * arboviruses Subject RIV: EE - Microbiology, Virology Impact factor: 5.228, year: 2015

  2. Prevalence of tick-borne encephalitis virus in Ixodes ricinus ticks in northern Europe with particular reference to Southern Sweden

    Science.gov (United States)

    2014-01-01

    Background In northern Europe, the tick-borne encephalitis virus (TBEV) of the European subtype is usually transmitted to humans by the common tick Ixodes ricinus. The aims of the present study are (i) to obtain up-to-date information on the TBEV prevalence in host-seeking I. ricinus in southern and central Sweden; (ii) to compile and review all relevant published records on the prevalence of TBEV in ticks in northern Europe; and (iii) to analyse and try to explain how the TBE virus can be maintained in natural foci despite an apparently low TBEV infection prevalence in the vector population. Methods To estimate the mean minimum infection rate (MIR) of TBEV in I. ricinus in northern Europe (i.e. Denmark, Norway, Sweden and Finland) we reviewed all published TBEV prevalence data for host-seeking I. ricinus collected during 1958–2011. Moreover, we collected 2,074 nymphs and 906 adults of I. ricinus from 29 localities in Sweden during 2008. These ticks were screened for TBEV by RT-PCR. Results The MIR for TBEV in nymphal and adult I. ricinus was 0.28% for northern Europe and 0.23% for southern Sweden. The infection prevalence of TBEV was significantly lower in nymphs (0.10%) than in adult ticks (0.55%). At a well-known TBEV-endemic locality, Torö island south-east of Stockholm, the TBEV prevalence (MIR) was 0.51% in nymphs and 4.48% in adults of I. ricinus. Conclusions If the ratio of nymphs to adult ticks in the TBEV-analysed sample differs from that in the I. ricinus population in the field, the MIR obtained will not necessarily reflect the TBEV prevalence in the field. The relatively low TBEV prevalence in the potential vector population recorded in most studies may partly be due to: (i) inclusion of uninfected ticks from the ‘uninfected areas’ surrounding the TBEV endemic foci; (ii) inclusion of an unrepresentative, too large proportion of immature ticks, compared to adult ticks, in the analysed tick pools; and (iii) shortcomings in the laboratory

  3. Comparison of Two Commercial Tick-Borne Encephalitis Virus IgG Enzyme-Linked Immunosorbent Assays.

    Science.gov (United States)

    Weissbach, Fabian H; Hirsch, Hans H

    2015-07-01

    Despite the availability of protective vaccines, tick-borne encephalitis virus (TBEV) infections have been increasingly reported to the European Centre for Disease Prevention and Control in the past 2 decades. Since the diagnosis of TBEV exposure relies on serological testing, we compared two commercial enzyme-linked immunosorbent assays (ELISAs), i.e., Immunozym FSME IgG assay (ELISA-1) and Euroimmun FSME Vienna IgG assay (ELISA-2). Both assays use whole TBEV antigens, but they differ in viral strains (Neudoerfl for ELISA-1 and K23 for ELISA-2) and cutoff values. In testing of samples from 398 healthy blood donors, ELISA-1 showed higher reactivity levels than ELISA-2 (P < 0.001), suggesting different assay properties. This finding was supported by Bland-Altman analysis of the optical density at 450 nm (OD450) (mean bias, +0.32 [95% limits of agreement, -0.31 to +0.95]) and persisted after transformation into Vienna units. Concordant results were observed for 276 sera (69%) (44 positive and 232 negative results). Discordant results were observed for 122 sera (31%); 15 were fully discordant, all being ELISA-1 positive and ELISA-2 negative, and 107 were partially discordant (101 being ELISA-1 indeterminate and ELISA-2 negative and 6 having positive or indeterminate reactivity in both ELISAs). Neutralization testing at a 1:10 dilution yielded positive results for 33 of 44 concordant positive sera, 1 of 15 fully discordant sera, and 1 of 33 partially discordant sera. Indirect immunofluorescence testing revealed high antibody titers of ≥100 for yellow fever virus in 18 cases and for dengue virus in one case, suggesting that cross-reactivity contributed to the ELISA-1 results. We conclude that (i) cross-reactivity among flaviviruses remains a limitation of TBEV serological testing, (ii) ELISA-2 revealed reasonable sensitivity and specificity for anti-TBEV IgG population screening of human sera, and (iii) neutralization testing is most specific and should be reserved

  4. Prevalence of tick-borne encephalitis virus in Ixodes ricinus ticks in northern Europe with particular reference to Southern Sweden.

    Science.gov (United States)

    Pettersson, John H-O; Golovljova, Irina; Vene, Sirkka; Jaenson, Thomas G T

    2014-03-11

    In northern Europe, the tick-borne encephalitis virus (TBEV) of the European subtype is usually transmitted to humans by the common tick Ixodes ricinus. The aims of the present study are (i) to obtain up-to-date information on the TBEV prevalence in host-seeking I. ricinus in southern and central Sweden; (ii) to compile and review all relevant published records on the prevalence of TBEV in ticks in northern Europe; and (iii) to analyse and try to explain how the TBE virus can be maintained in natural foci despite an apparently low TBEV infection prevalence in the vector population. To estimate the mean minimum infection rate (MIR) of TBEV in I. ricinus in northern Europe (i.e. Denmark, Norway, Sweden and Finland) we reviewed all published TBEV prevalence data for host-seeking I. ricinus collected during 1958-2011. Moreover, we collected 2,074 nymphs and 906 adults of I. ricinus from 29 localities in Sweden during 2008. These ticks were screened for TBEV by RT-PCR. The MIR for TBEV in nymphal and adult I. ricinus was 0.28% for northern Europe and 0.23% for southern Sweden. The infection prevalence of TBEV was significantly lower in nymphs (0.10%) than in adult ticks (0.55%). At a well-known TBEV-endemic locality, Torö island south-east of Stockholm, the TBEV prevalence (MIR) was 0.51% in nymphs and 4.48% in adults of I. ricinus. If the ratio of nymphs to adult ticks in the TBEV-analysed sample differs from that in the I. ricinus population in the field, the MIR obtained will not necessarily reflect the TBEV prevalence in the field. The relatively low TBEV prevalence in the potential vector population recorded in most studies may partly be due to: (i) inclusion of uninfected ticks from the 'uninfected areas' surrounding the TBEV endemic foci; (ii) inclusion of an unrepresentative, too large proportion of immature ticks, compared to adult ticks, in the analysed tick pools; and (iii) shortcomings in the laboratory techniques used to detect the virus that may be

  5. Targeted blockade in lethal West Nile virus encephalitis indicates a crucial role for very late antigen (VLA-4-dependent recruitment of nitric oxide-producing macrophages

    Directory of Open Access Journals (Sweden)

    Getts Daniel R

    2012-10-01

    Full Text Available Abstract Infiltration of Ly6Chi monocytes from the blood is a hallmark of viral encephalitis. In mice with lethal encephalitis caused by West Nile virus (WNV, an emerging neurotropic flavivirus, inhibition of Ly6Chi monocyte trafficking into the brain by anti-very late antigen (VLA-4 integrin antibody blockade at the time of first weight loss and leukocyte influx resulted in long-term survival of up to 60% of infected mice, with subsequent sterilizing immunity. This treatment had no effect on viral titers but appeared to be due to inhibition of Ly6Chi macrophage immigration. Although macrophages isolated from the infected brain induced WNV-specific CD4+ T-cell proliferation, T cells did not directly contribute to pathology, but are likely to be important in viral control, as antibody-mediated T-cell depletion could not reproduce the therapeutic benefit of anti-VLA-4. Instead, 70% of infiltrating inflammatory monocyte-derived macrophages were found to be making nitric oxide (NO. Furthermore, aminoguanidine-mediated inhibition of induced NO synthase activity in infiltrating macrophages significantly prolonged survival, indicating involvement of NO in the immunopathology. These data show for the first time the therapeutic effects of temporally targeting pathogenic NO-producing macrophages during neurotropic viral encephalitis.

  6. Role of Cytokines and Neurotrophins in the Central Nervous System in Venezuelan Equine Encephalitis Virus Pathogenesis

    Science.gov (United States)

    2001-01-01

    for Guillain Barr Syndrome , an acute demyelinating inflammatory polyneuropathy. EAN is also suppressed by treatment with TGF-ß (29). The absence of...Schoneboom. 35 Guillain Barr Syndrome (GBS). GBS patients display elevated levels of IL-6 in their cerebrospinal fluid, but the significance of this...Deficiency Syndrome ALS Amylotrophic Lateral Scleropathy BDNF Brain derived neurotrophic factor BDV Borna Disease Virus CNTF Ciliary neurotrophic

  7. Live, Attenuated Venezuelan Equine Encephalitis Virus Vaccine (TC83) Causes Persistent Brain Infection in Mice with Non-functional αβ T-Cells

    Science.gov (United States)

    Taylor, Katherine; Kolokoltsova, Olga; Ronca, Shannon E.; Estes, Mark; Paessler, Slobodan

    2017-01-01

    Intranasal infection with vaccine strain of Venezuelan equine encephalitis virus (TC83) caused persistent viral infection in the brains of mice without functional αβ T-cells (αβ-TCR -/-). Remarkably, viral kinetics, host response gene transcripts and symptomatic disease are similar between αβ-TCR -/- and wild-type C57BL/6 (WT) mice during acute phase of infection [0–13 days post-infection (dpi)]. While WT mice clear infectious virus in the brain by 13 dpi, αβ-TCR -/- maintain infectious virus in the brain to 92 dpi. Persistent brain infection in αβ-TCR -/- correlated with inflammatory infiltrates and elevated cytokine protein levels in the brain at later time points. Persistent brain infection of αβ-TCR -/- mice provides a novel model to study prolonged alphaviral infection as well as the effects and biomarkers of long-term viral inflammation in the brain. PMID:28184218

  8. Tick borne encephalitis without cerebrospinal fluid pleocytosis

    OpenAIRE

    Stupica, Daša; Strle, Franc; Avšič-Županc, Tatjana; Logar, Mateja; Pečavar, Blaž; Bajrović, Fajko F

    2014-01-01

    Background Tick borne encephalitis is the most frequent vector-transmitted infectious disease of the central nervous system in Europe and Asia. The disease caused by European subtype of tick borne encephalitis virus has typically a biphasic clinical course with the second phase presenting as meningitis, meningoencephalitis, or meningoencephalomyelitis. Cerebrospinal fluid pleocytosis is considered a condition sine qua non for the diagnosis of neurologic involvement in tick borne encephalitis,...

  9. Infected dendritic cells are sufficient to mediate the adjuvant activity generated by Venezuelan equine encephalitis virus replicon particles.

    Science.gov (United States)

    Tonkin, Daniel R; Whitmore, Alan; Johnston, Robert E; Barro, Mario

    2012-06-22

    Replicon particles derived from Venezuelan equine encephalitis virus (VEE) are infectious non-propagating particles which act as a safe and potent systemic, mucosal, and cellular adjuvant when delivered with antigen. VEE and VEE replicon particles (VRP) can target multiple cell types including dendritic cells (DCs). The role of these cell types in VRP adjuvant activity has not been previously evaluated, and for these studies we focused on the contribution of DCs to the response to VRP. By analysis of VRP targeting in the draining lymph node, we found that VRP induced rapid recruitment of TNF-secreting monocyte-derived inflammatory dendritic cells. VRP preferentially infected these inflammatory DCs as well as classical DCs and macrophages, with less efficient infection of other cell types. DC depletion suggested that the interaction of VRP with classical DCs was required for recruitment of inflammatory DCs, induction of high levels of many cytokines, and for stable transport of VRP to the draining lymph node. Additionally, in vitro-infected DCs enhanced antigen-specific responses by CD4 and CD8 T cells. By transfer of VRP-infected DCs into mice we showed that these DCs generated an inflammatory state in the draining lymph node similar to that achieved by VRP injection. Most importantly, VRP-infected DCs were sufficient to establish robust adjuvant activity in mice comparable to that produced by VRP injection. These findings indicate that VRP infect, recruit and activate both classical and inflammatory DCs, and those DCs become mediators of the VRP adjuvant activity. Published by Elsevier Ltd.

  10. Japanese Encephalitis Virus Infection Rate and Detection of Genotype I From Culex tritaeniorhynchus Collected From Jiangsu, China.

    Science.gov (United States)

    Chu, Hongliang; Wu, Zhiming; Chen, Hongna; Li, Chunxiao; Guo, Xiaoxia; Liu, Ran; Wang, Gang; Zhou, Minghao; Zhao, Tongyan

    2017-07-01

    Information regarding the infection rate and genotype shifts for Japanese encephalitis virus (JEV) are important for JE vaccine application. In Jiangsu province, China, which is one of the provinces with a high prevalence of JE, JEV infection in swine and mosquitoes in certain cities has only been investigated in 2008-2009. Lianyungang City has one of the highest numbers of JE cases in Jiangsu province, and it has a high risk of JEV invasion via migrant birds. JEV infection in vectors in Lianyungang City, which has urban and rural parts, has not been investigated. In 2015-2016, we collected mosquitoes in cowsheds with ultraviolet light traps and detected JEV by reverse transcription-polymerase chain reaction (RT-PCR) method in Culex tritaeniorhynchus in Xintan village, Xuzhuang village, and Xiaogaozhuang village in Lianyungang City, China. The proportion of positive pools, which is calculated by the number of infected pools to the total number of pools tested in these villages, were 16.67%, 20.00%, and 4.17%, respectively, and the minimum infection rates, which is calculated as the ratio of the number of positive pools to the total number of mosquitoes tested, were 3.33‰, 4.00‰, and 0.83‰, respectively. Four JEV strains from positive samples were coded as LYG-1, LYG-2, LYG-3, and LYG-4, and the complete E genes were sequenced. Furthermore, the complete genome of LYG-3 was sequenced. The phylogenetic analysis indicated that all the four JEV strains belonged to genotype I-b. This is the first report of genotype I JEV strain in Jiangsu province. The high JEV infection rate in Culex tritaeniorhynchus indicated a high risk of JE reemergence in Lianyungang. The detected JEV strains may have similar antigenicity to that of SA14-14-2 according to molecular characters. These findings suggest that the vaccine can still be effective in Lianyungang.

  11. EXPERIMENTAL STUDIES ON ENCEPHALITIS

    Science.gov (United States)

    Webster, Leslie T.; Clow, Anna D.; Bauer, Johannes H.

    1935-01-01

    Anopheles quadrimaculatus mosquitoes, fed on mice in which encephalitis virus (St. Louis type) is present in the blood stream, take up and retain the virus for the duration of their lives. The titre of the virus in mosquitoes 4 hours after engorging on mice with a maximum blood stream infection represents about 10,000 lethal mouse intracerebral doses per mosquito. This titre drops during the following 2 weeks to about 100 lethal doses per mosquito, but from the 3rd week to the death of the mosquito, usually increases to approximately the original level and remains there. The titre of virus in mosquitoes which have engorged on mouse blood containing smaller quantities of virus exhibits the same drop and subsequent rise to the original level. The virus-containing mosquitoes did not infect mice or monkeys by biting. PMID:19870373

  12. Rasmussen's Encephalitis

    Science.gov (United States)

    ... severe seizures, loss of motor skills and speech, paralysis on one side of the body (hemiparesis), inflammation of the brain (encephalitis), and mental deterioration. Most individuals with Rasmussen’s ...

  13. Nonconvulsive Status Epilepticus Complicating Epstein-Barr Virus Encephalitis in a Child

    Directory of Open Access Journals (Sweden)

    Filippo Greco

    2014-01-01

    Full Text Available Children with acute encephalopathy show prolonged electrographic seizure activity consistent with nonconvulsive status epilepticus (NCSE. Pediatric NCSE is a heterogeneous clinical entity with poor outcome and different etiologies, including central nervous system infection, stroke, toxic-metabolic syndrome, and epileptic syndrome. We report a 4-year-old girl with seizure and behavioral changes in whom the analysis of cerebrospinal fluid by polymerase chain reaction was positive for Epstein-Barr virus. We emphasize the importance of electroencephalography (EEG, and particularly, of continuous EEG monitoring for early recognition and appropriate treatment of this condition.

  14. Characterization of a new 5' splice site within the caprine arthritis encephalitis virus genome: evidence for a novel auxiliary protein

    Directory of Open Access Journals (Sweden)

    Perrin Cécile

    2008-02-01

    Full Text Available Abstract Background Lentiviral genomes encode multiple structural and regulatory proteins. Expression of the full complement of viral proteins is accomplished in part by alternative splicing of the genomic RNA. Caprine arthritis encephalitis virus (CAEV and maedi-visna virus (MVV are two highly related small-ruminant lentiviruses (SRLVs that infect goats and sheep. Their genome seems to be less complex than those of primate lentiviruses since SRLVs encode only three auxiliary proteins, namely, Tat, Rev, and Vif, in addition to the products of gag, pol, and env genes common to all retroviruses. Here, we investigated the central part of the SRLV genome to identify new splice elements and their relevance in viral mRNA and protein expression. Results We demonstrated the existence of a new 5' splice (SD site located within the central part of CAEV genome, 17 nucleotides downstream from the SD site used for the rev mRNA synthesis, and perfectly conserved among SRLV strains. This new SD site was found to be functional in both transfected and infected cells, leading to the production of a transcript containing an open reading frame generated by the splice junction with the 3' splice site used for the rev mRNA synthesis. This open reading frame encodes two major protein isoforms of 18- and 17-kDa, named Rtm, in which the N-terminal domain shared by the Env precursor and Rev proteins is fused to the entire cytoplasmic tail of the transmembrane glycoprotein. Immunoprecipitations using monospecific antibodies provided evidence for the expression of the Rtm isoforms in infected cells. The Rtm protein interacts specifically with the cytoplasmic domain of the transmembrane glycoprotein in vitro, and its expression impairs the fusion activity of the Env protein. Conclusion The characterization of a novel CAEV protein, named Rtm, which is produced by an additional multiply-spliced mRNA, indicated that the splicing pattern of CAEV genome is more complex than

  15. Circulation of Eastern equine encephalitis, Western equine encephalitis, Ilhéus, Maguari and Tacaiuma viruses in equines of the Brazilian Pantanal, South America Circulação dos virus das encefalites equina do Leste e Oeste, Ilhéus, Maguari e Tacaiuma em equinos da região do Pantanal brasileiro, América do Sul

    Directory of Open Access Journals (Sweden)

    Lygia Busch Iversson

    1993-08-01

    Full Text Available Neutralizing antibodies to EEE (6.7%, WEE (1.2%, ILH (26.6%, MAG (28.2% and TCM (15.7% viruses were found in sera of 432 equines of the Brazilian Pantanal, area where undiagnosed horse deaths are frequently observed. A 4-fold rise in CF titer to EEE virus was detected in acute and convalescent sera of an encephalitis horse sacrified in 1992. Antibodies to EEE, ILH, MAG and TCM viruses were detected in horses less than 2 years old indicating recent circulation of these viruses in the Pantanal. The evidence of recent equine encephalitis associated with rising CF titer to EEE warrants a more intensive study with attempts to isolate virus from horses with clinical manifestations of encephalitis.Em um inquérito sorológico realizado em 432 equinos da região do Pantanal, território brasileiro, foram detectados anticorpos neutralizantes para os vírus EEE (6,7%, WEE (1,2%, ILH (26,6%, MAG (28,2% e TCM (15,7%. Detectou-se também em um cavalo com um quadro clínico de encefalite um aumento de 4 vezes no título de anticorpos fixadores de complemento para EEE em soros coletados nas fases aguda e convalescente da doença. Cavalos com menos de 2 anos de idade apresentaram anticorpos neutralizantes para EEE, ILH, MAG e TCM, indicando circulação recente desses vírus no Pantanal. Os achados justificam intensificar esses estudos na região com tentativas de isolamento de vírus de animais apresentando manifestações clínicas de encefalite.

  16. Detection and differentiation of genotype I and III Japanese encephalitis virus in mosquitoes by multiplex reverse transcriptase-polymerase chain reaction.

    Science.gov (United States)

    Chen, Y Y; Lin, J W; Fan, Y C; Chiou, S S

    2014-02-01

    Japanese encephalitis (JE) is a disease that threatens both human and animal populations in Asian countries, and the causative agent of JE, Japanese encephalitis virus (JEV), has recently changed from genotype III (GIII) to genotype I (GI). However, a test for the rapid differentiation of GI and GIII JEV is still unavailable, especially one that can be used for mosquito-based surveillance. We have designed GI- and GIII-specific primer sets for the rapid detection and differentiation of GI and GIII JEV by multiplex reverse transcriptase-polymerase chain reaction (multiplex RT-PCR). The GI-specific and GIII-specific primer sets were able to specifically amplify the target gene from GI and GIII JEV, respectively. The limitations of detection were 0.00225 and 0.225 pfu for the GI-specific and GIII-specific primers, respectively. Using a mixture of GI-specific and GIII-specific primers, the multiplex RT-PCR was able to specifically detect and differentiate GI and GIII JEV. The multiplex RT-PCR was able to successfully differentiate GI and GIII virus in JEV-infected mosquitoes. Thus, a sensitive and specific multiplex RT-PCR system for the rapid detection and differentiation of GI and GIII JEV has been developed, and this test is likely to be valuable when carrying out mosquito-based JEV surveillance. © 2012 Blackwell Verlag GmbH.

  17. Prevalence of tick borne encephalitis virus in tick nymphs in relation to climatic factors on the southern coast of Norway

    Directory of Open Access Journals (Sweden)

    Andreassen Ashild

    2012-08-01

    Full Text Available Abstract Background Tick-borne encephalitis (TBE is among the most important vector borne diseases of humans in Europe and is currently identified as a major health problem in many countries. TBE endemic zones have expanded over the past two decades, as well as the number of reported cases within endemic areas. Multiple factors are ascribed for the increased incidence of TBE, including climatic change. The number of TBE cases has also increased in Norway over the past decade, and the human cases cluster along the southern coast of Norway. In Norway the distribution and prevalence of TBE virus (TBEV in tick populations is largely unknown. The objectives of this study were to estimate the TBEV prevalence in Ixodes ricinus from seven locations and to assess the relationship between the TBEV prevalence and site-specific climatic variables. Methods A total of 5630 questing nymphs were collected and analyzed in pools of ten. All pools were screened with an in-house real-time RT-PCR, and the positive pools were pyrosequenced. Two methods, minimum infection rate (MIR and a frequentist method (EPP for pooled prevalence estimations were calculated and compared. Climatic data were descriptively compared to the corresponding EPP of each location in order to explain variations in TBEV prevalence. Results The seven foci of TBEV had an estimated overall prevalence (EPP in pools of nymphs combined, of 0.53% with 95% CI (0.35–0.75, with point prevalence ranging between 0.11%–1.22%. The sites with the highest point prevalences were within the municipalities which had the highest numbers of registered TBE cases. The results indicate that the location with highest point prevalence had the highest relative mean humidity and lowest mean saturation deficit and vice versa for the lowest EPP. Conclusion Our study confirms the existence of TBEV endemic foci in Norway. These results are of importance to increase the awareness of TBEV infections in Norway and could be

  18. Distinct dictation of Japanese encephalitis virus-induced neuroinflammation and lethality via triggering TLR3 and TLR4 signal pathways.

    Science.gov (United States)

    Han, Young Woo; Choi, Jin Young; Uyangaa, Erdenebelig; Kim, Seong Bum; Kim, Jin Hyoung; Kim, Bum Seok; Kim, Koanhoi; Eo, Seong Kug

    2014-09-01

    Japanese encephalitis (JE) is major emerging neurologic disease caused by JE virus. To date, the impact of TLR molecules on JE progression has not been addressed. Here, we determined whether each TLR modulates JE, using several TLR-deficient mouse strains (TLR2, TLR3, TLR4, TLR7, TLR9). Surprisingly, among the tested TLR-deficient mice there were contrasting results in TLR3(-/-) and TLR4(-/-) mice, i.e. TLR3(-/-) mice were highly susceptible to JE, whereas TLR4(-/-) mice showed enhanced resistance to JE. TLR3 ablation induced severe CNS inflammation characterized by early infiltration of inflammatory CD11b(+)Ly-6Chigh monocytes along with profoundly increased viral burden, proinflammatory cytokine/chemokine expression as well as BBB permeability. In contrast, TLR4(-/-) mice showed mild CNS inflammation manifested by reduced viral burden, leukocyte infiltration and proinflammatory cytokine expression. Interestingly, TLR4 ablation provided potent in vivo systemic type I IFN innate response, as well as ex vivo type I IFN production associated with strong induction of antiviral PRRs (RIG-I, MDA5), transcription factors (IRF-3, IRF-7), and IFN-dependent (PKR, Oas1, Mx) and independent ISGs (ISG49, ISG54, ISG56) by alternative activation of IRF3 and NF-κB in myeloid-derived DCs and macrophages, as compared to TLR3(-/-) myeloid-derived cells which were more permissive to viral replication through impaired type I IFN innate response. TLR4 ablation also appeared to mount an enhanced type I IFN innate and humoral, CD4(+) and CD8(+) T cell responses, which were mediated by altered immune cell populations (increased number of plasmacytoid DCs and NK cells, reduced CD11b(+)Ly-6C(high) monocytes) and CD4(+)Foxp3(+) Treg number in lymphoid tissue. Thus, potent type I IFN innate and adaptive immune responses in the absence of TLR4 were closely coupled with reduced JE lethality. Collectively, these results suggest that a balanced triggering of TLR signal array by viral components

  19. Distinct dictation of Japanese encephalitis virus-induced neuroinflammation and lethality via triggering TLR3 and TLR4 signal pathways.

    Directory of Open Access Journals (Sweden)

    Young Woo Han

    2014-09-01

    Full Text Available Japanese encephalitis (JE is major emerging neurologic disease caused by JE virus. To date, the impact of TLR molecules on JE progression has not been addressed. Here, we determined whether each TLR modulates JE, using several TLR-deficient mouse strains (TLR2, TLR3, TLR4, TLR7, TLR9. Surprisingly, among the tested TLR-deficient mice there were contrasting results in TLR3(-/- and TLR4(-/- mice, i.e. TLR3(-/- mice were highly susceptible to JE, whereas TLR4(-/- mice showed enhanced resistance to JE. TLR3 ablation induced severe CNS inflammation characterized by early infiltration of inflammatory CD11b(+Ly-6Chigh monocytes along with profoundly increased viral burden, proinflammatory cytokine/chemokine expression as well as BBB permeability. In contrast, TLR4(-/- mice showed mild CNS inflammation manifested by reduced viral burden, leukocyte infiltration and proinflammatory cytokine expression. Interestingly, TLR4 ablation provided potent in vivo systemic type I IFN innate response, as well as ex vivo type I IFN production associated with strong induction of antiviral PRRs (RIG-I, MDA5, transcription factors (IRF-3, IRF-7, and IFN-dependent (PKR, Oas1, Mx and independent ISGs (ISG49, ISG54, ISG56 by alternative activation of IRF3 and NF-κB in myeloid-derived DCs and macrophages, as compared to TLR3(-/- myeloid-derived cells which were more permissive to viral replication through impaired type I IFN innate response. TLR4 ablation also appeared to mount an enhanced type I IFN innate and humoral, CD4(+ and CD8(+ T cell responses, which were mediated by altered immune cell populations (increased number of plasmacytoid DCs and NK cells, reduced CD11b(+Ly-6C(high monocytes and CD4(+Foxp3(+ Treg number in lymphoid tissue. Thus, potent type I IFN innate and adaptive immune responses in the absence of TLR4 were closely coupled with reduced JE lethality. Collectively, these results suggest that a balanced triggering of TLR signal array by viral components

  20. Simultaneous detection and differentiation of dengue virus serotypes 1-4, Japanese encephalitis virus, and West Nile virus by a combined reverse-transcription loop-mediated isothermal amplification assay

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    Yin Jianhua

    2011-07-01

    Full Text Available Abstract Background Rapid identification and differentiation of mosquito-transmitted flaviviruses in acute-phase sera of patients and field-caught vector mosquitoes are important for the prediction and prevention of large-scale epidemics. Results We developed a flexible reverse-transcription loop-mediated isothermal amplification (RT-LAMP unit for the detection and differentiation of dengue virus serotypes 1-4 (DENV1-4, Japanese encephalitis virus (JEV, and West Nile virus (WNV. The unit efficiently amplified the viral genomes specifically at wide ranges of viral template concentrations, and exhibited similar amplification curves as monitored by a real-time PCR engine. The detection limits of the RT-LAMP unit were 100-fold higher than that of RT-PCR in 5 of the six flaviviruses. The results on specificity indicated that the six viruses in the assay had no cross-reactions with each other. By examining 66 viral strains of DENV1-4 and JEV, the unit identified the viruses with 100% accuracy and did not cross-react with influenza viruses and hantaviruses. By screening a panel of specimens containing sera of 168 patients and 279 pools of field-caught blood sucked mosquitoes, results showed that this unit is high feasible in clinical settings and epidemiologic field, and it obtained results 100% correlated with real-time RT-PCR. Conclusions The RT-LAMP unit developed in this study is able to quickly detect and accurately differentiate the six kinds of flaviviruses, which makes it extremely feasible for screening these viruses in acute-phase sera of the patients and in vector mosquitoes without the need of high-precision instruments.

  1. Eilat virus host range restriction is present at multiple levels of the virus life cycle.

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    Nasar, Farooq; Gorchakov, Rodion V; Tesh, Robert B; Weaver, Scott C

    2015-01-15

    Most alphaviruses are mosquito-borne and exhibit a broad host range, infecting many different vertebrates, including birds, rodents, equids, humans, and nonhuman primates. This ability of most alphaviruses to infect arthropods and vertebrates is essential for their maintenance in nature. Recently, a new alphavirus, Eilat virus (EILV), was described, and in contrast to all other mosquito-borne viruses, it is unable to replicate in vertebrate cell lines. Investigations into the nature of its host range restriction showed the inability of genomic EILV RNA to replicate in vertebrate cells. Here, we investigated whether the EILV host range restriction is present at the entry level and further explored the viral factors responsible for the lack of genomic RNA replication. Utilizing Sindbis virus (SINV) and EILV chimeras, we show that the EILV vertebrate host range restriction is also manifested at the entry level. Furthermore, the EILV RNA replication restriction is independent of the 3' untranslated genome region (UTR). Complementation experiments with SINV suggested that RNA replication is restricted by the inability of the EILV nonstructural proteins to form functional replicative complexes. These data demonstrate that the EILV host range restriction is multigenic, involving at least one gene from both nonstructural protein (nsP) and structural protein (sP) open reading frames (ORFs). As EILV groups phylogenetically within the mosquito-borne virus clade of pathogenic alphaviruses, our findings have important evolutionary implications for arboviruses. Our work explores the nature of host range restriction of the first "mosquito-only alphavirus," EILV. EILV is related to pathogenic mosquito-borne viruses (Eastern equine encephalitis virus [EEEV], Western equine encephalitis virus [WEEV], Venezuelan equine encephalitis virus [VEEV], and Chikungunya virus [CHIKV]) that cause severe disease in humans. Our data demonstrate that EILV is restricted both at entry and genomic

  2. The NS3 and NS4A genes as the targets of RNA interference inhibit replication of Japanese encephalitis virus in vitro and in vivo.

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    Yuan, Lei; Wu, Rui; Liu, Hanyang; Wen, Xintian; Huang, Xiaobo; Wen, Yiping; Ma, Xiaoping; Yan, Qigui; Huang, Yong; Zhao, Qin; Cao, Sanjie

    2016-12-15

    Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that can cause acute encephalitis with a high fatality rate. RNA interference (RNAi) is a powerful tool to silence gene expression and a potential therapy for virus infection. In this study, the antiviral ability of eight shRNA expression plasmids targeting different sites of the NS3 and NS4A genes of JEV was determined in BHK21 cells and mice. The pGP-NS3-3 and pGP-NS4A-4 suppressed 93.9% and 82.0% of JEV mRNA in cells, respectively. The virus titer in cells was reduced approximately 950-fold by pretreating with pGP-NS3-4, and 640-fold by pretreating with pGP-NS4A-4. The results of western blot and immunofluorescence analysis showed JEV E protein and viral load in cells were remarkably inhibited by shRNA expression plasmids. The viral load in brains of mice pretreated with pGP-NS3-4 or pGP-NS4A-4 were reduced approximately 2400-fold and 800-fold, respectively, and the survival rate of mice challenged with JEV were 70% and 50%, respectively. However, the antiviral ability of shRNA expression plasmids was decreased over time. This study indicates that RNAi targeting of the NS3 and NS4A genes of JEV can sufficiently inhibit the replication of JEV in vitro and in vivo, and NS3 and NS4A genes might be potential targets of molecular therapy for JEV infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Identification and Analysis of Differentially-Expressed microRNAs in Japanese Encephalitis Virus-Infected PK-15 Cells with Deep Sequencing

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    Yuhan Cai

    2015-01-01

    Full Text Available Japanese encephalitis virus (JEV, a mosquito-borne Flavivirus, causes acute viral encephalitis with high morbidity and mortality in humans and animals. MicroRNAs (miRNAs are small noncoding RNAs that are important modulators of the intricate host-pathogen interaction networks. However, our knowledge of the changes that occur in miRNAs in host cells after JEV infection is still limited. To understand the molecular pathogenesis of JEV at the level of posttranscriptional regulation, we used Illumina deep sequencing to sequence two small RNA libraries prepared from PK-15 cells before and after JEV infection. We identified 522 and 427 miRNAs in the infected and uninfected cells, respectively. Overall, 132 miRNAs were expressed significantly differently after challenge with JEV: 78 were upregulated and 54 downregulated. The sequencing results for selected miRNAs were confirmed with RT-qPCR. GO analysis of the host target genes revealed that these dysregulated miRNAs are involved in complex cellular pathways, including the metabolic pathway, inflammatory response and immune response. To our knowledge, this is the first report of the comparative expression of miRNAs in PK-15 cells after JEV infection. Our findings will underpin further studies of miRNAs’ roles in JEV replication and identify potential candidates for antiviral therapies against JEV.

  4. Activated CD56(+) lymphocytes (NK+NKT) mediate immunomodulatory and anti-viral effects during Japanese encephalitis virus infection of dendritic cells in-vitro.

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    Sooryanarain, Harini; Ayachit, Vijay; Gore, Milind

    2012-10-25

    Japanese encephalitis virus (JEV) remains one of the major causative agents of pediatric encephalitis. Interaction of dendritic cells (DCs) with innate lymphocytes (NK and NKT) represents a crucial event during anti-viral innate immune response. In the current study, we have tried to understand the interaction between JEV, human monocyte derived DCs (MDDCs), and CD56(+) cells (NK+NKT) in-vitro. We have used two JEV strains (i) JE057434 (neurovirulent, wild-type) and (ii) SA14-14-2 (non-neurovirulent, live-attenuated vaccine) to investigate the effect of viral virulence on the functional status of primary human MDDCs. Our preliminary results indicate that replicating JEV induces MDDCs maturation via PI3K and p38 pathways. We also show that the presence of IL2-activated CD56(+) cells impart both immunomodulatory and anti-viral effects on DCs infected with JEV. Mechanistic studies illustrate that, IL2-activated CD56(+) lymphocytes mediated immunomodulation occurs through direct cell-to-cell contact and TNFα, while the anti-viral effect is dependent on direct cell-to-cell contact. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Rapid and simple detection of Japanese encephalitis virus by reverse transcription loop-mediated isothermal amplification combined with a lateral flow dipstick.

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    Deng, Jieru; Pei, Jingjing; Gou, Hongchao; Ye, Zuodong; Liu, Cuicui; Chen, Jinding

    2015-03-01

    Japanese encephalitis virus (JEV) is a major cause of viral encephalitis in geographical areas, such as Asia and Western Pacific, where it is a threat to human and animal health. To control this disease, it is necessary to develop a rapid, simple, accurate method for diagnosis. In this study, a method based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) coupled with a lateral flow dipstick (LFD) has been developed to detect JEV (JEV RT-LAMP-LFD). The entire assay can be completed within 70 min, and in this study, no false positive results were observed when other pathogens were tested, indicating that the assay is a highly specific method for the detection of JEV. Additionally, the sensitivity of the RT-LAMP-LFD assay for SA14-14-2 strain was 50 pg of RNA, which was similar to that of RT-PCR and RT-LAMP combined with gel electrophoresis, and was 10-fold more sensitive than RT-LAMP combined with calcein. The limit of detection for this assay was 5 pg of RNA. In addition, no false positive results were obtained with 14 serum samples. Our results indicate that this RT-LAMP-LFD assay will be of great value for JEV infection testing due to its rapid and highly specific and sensitive properties. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Herpes simplex encephalitis with thalamic, brainstem and cerebellar involvement.

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    Garg, Meenal; Kulkarni, Shilpa; Udwadia Hegde, Anaita

    2017-01-01

    Herpes simplex virus encephalitis is a common and treatable cause of acute encephalitis in all age groups. Certain radiological features such as temporal parenchymal involvement facilitate the diagnosis. The use of herpes simplex virus polymerase chain reaction has expanded the clinical and imaging spectrum. We report the case of a young patient who presented with a movement disorder and predominant involvement of thalami, brainstem and cerebellum on magnetic resonance imaging, and was diagnosed with herpes simplex virus encephalitis. Differentiation from Japanese encephalitis may be difficult in these patients, especially in endemic areas, and may necessitate the use of relevant investigations in all patients.

  7. Natural variation in the heparan sulfate binding domain of the eastern equine encephalitis virus E2 glycoprotein alters interactions with cell surfaces and virulence in mice.

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    Gardner, Christina L; Choi-Nurvitadhi, Jo; Sun, Chengqun; Bayer, Avraham; Hritz, Jozef; Ryman, Kate D; Klimstra, William B

    2013-08-01

    Recently, we compared amino acid sequences of the E2 glycoprotein of natural North American eastern equine encephalitis virus (NA-EEEV) isolates and demonstrated that naturally circulating viruses interact with heparan sulfate (HS) and that this interaction contributes to the extreme neurovirulence of EEEV (C. L. Gardner, G. D. Ebel, K. D. Ryman, and W. B. Klimstra, Proc. Natl. Acad. Sci. U. S. A., 108:16026-16031, 2011). In the current study, we have examined the contribution to HS binding of each of three lysine residues in the E2 71-to-77 region that comprise the primary HS binding site of wild-type (WT) NA-EEEV viruses. We also report that the original sequence comparison identified five virus isolates, each with one of three amino acid differences in the E2 71-to-77 region, including mutations in residues critical for HS binding by the WT virus. The natural variant viruses, which possessed either a mutation from lysine to glutamine at E2 71, a mutation from lysine to threonine at E2 71, or a mutation from threonine to lysine at E2 72, exhibited altered interactions with heparan sulfate and cell surfaces and altered virulence in a mouse model of EEEV disease. An electrostatic map of the EEEV E1/E2 heterotrimer based upon the recent Chikungunya virus crystal structure (J. E. Voss, M. C. Vaney, S. Duquerroy, C. Vonrhein, C. Girard-Blanc, E. Crublet, A. Thompson, G. Bricogne, and F. A. Rey, Nature, 468:709-712, 2010) showed the HS binding site to be at the apical surface of E2, with variants affecting the electrochemical nature of the binding site. Together, these results suggest that natural variation in the EEEV HS binding domain may arise during EEEV sylvatic cycles and that this variation may influence receptor interaction and the severity of EEEV disease.

  8. Detection of specific IgG antibodies in blood donors and tick-borne encephalitis virus in ticks within a non-endemic area in southeast Norway.

    Science.gov (United States)

    Larsen, Astri Lervik; Kanestrøm, Anita; Bjørland, Marthe; Andreassen, Ashild; Soleng, Arnulf; Vene, Sirkka; Dudman, Susanne G

    2014-03-01

    Tick-borne encephalitis (TBE) is an emerging tick-borne disease in Europe. In Norway, the first TBE case occurred in 1997, and since then 1-14 cases have been detected annually along the southern coast. No TBE cases have yet been notified from the eastern coastal area. This study was conducted to assess the need for diagnostic tests and vaccine recommendation for this part of Norway. Four hundred and sixty-one blood donors living in the county of Østfold were enrolled. After informed consent was obtained, the participants submitted a blood sample and filled out a questionnaire regarding tick bites, outdoor activities, and Flavivirus vaccines and diseases. Ixodes ricinus ticks were collected from the immediate vicinity and were examined in pools of 10 for TBE virus. Eight human samples were TBE virus IgG-positive by ELISA and 5 of these samples were confirmed positive by neutralization test. Excluding the 2 samples from participants who had reported previous TBE vaccination, this shows a seroprevalence among blood donors of 0.65%. The existence of TBEV in the region was verified in nymphs of Ixodes ricinus by a prevalence of 0.14%. The seroprevalence of TBE virus IgG and the TBE virus detected in ticks, indicate that TBE cases could occasionally occur in the area. The results should be made available to health care personnel to raise awareness for preventative measures.

  9. Travel-acquired Japanese encephalitis and vaccination considerations.

    Science.gov (United States)

    Pavli, Androula; Maltezou, Helena C

    2015-09-27

    Japanese encephalitis (JE) is a serious arboviral disease caused by a virus of the genus Flavivirus. Japanese encephalitis is the most common vaccine-preventable virus causing encephalitis in Asia, affecting more than 50,000 persons and leading to 15,000 fatalities per year in endemic countries. For most travelers to Asia, the risk of Japanese encephalitis infection is extremely low and depends on destination, duration of travel, season, and activities. This article reviews travel-acquired Japanese encephalitis with a focus on epidemiology and prevention in the light of the newly available options for active immunization against Japanese encephalitis which have become available, and of the increasing popularity of travels to Japanese encephalitis endemic countries.

  10. Immunogenicity of a Japanese encephalitis chimeric virus vaccine as a booster dose after primary vaccination with SA14-14-2 vaccine in Thai children.

    Science.gov (United States)

    Janewongwirot, Pakpoom; Puthanakit, Thanyawee; Anugulruengkitt, Suvaporn; Jantarabenjakul, Watsamon; Phasomsap, Chayapa; Chumket, Sompong; Yoksan, Sutee; Pancharoen, Chitsanu

    2016-10-17

    Japanese Encephalitis chimeric virus vaccine (JE-CV) and SA14-14-2 vaccine are live-attenuated JE vaccines produced from the same virus strain. Data on interchangeability is limited. To evaluate the immunogenicity and safety of JE-CV booster after primary vaccination with SA14-14-2 vaccine. This study was an open-label clinical trial in Thai children who had received a primary SA14-14-2 vaccination at 12-24monthsbefore enrollment (ClinicalTrials.gov NCT02602652). JE-CV was administered. A 50% plaque reduction neutralization test (PRNT 50 ) against three virus strains; JE-CV, SA-14-14-2andwild-type JE virus was measured before and 28-days post vaccination. The laboratory was performed at PRNT 50 titers ⩾10 (1/dil) were considered seroprotective against JE. Geometric mean titer (GMT) of PRNT 50 was calculated. Adverse events were observed for 28days. From March 2014 to June 2015, 50 children (64% male) were enrolled. Mean age and duration after primary vaccination was 26.9 (SD 4.6) and 12.8 (SD 2.7) months, respectively. The proportion of participants who had PRNT 50 pre and post-booster vaccination were 92% and 96% against JE-CV virus, 56% and 98% against SA-14-14-2 strain and 70% and 98% against wild-type JE virus, respectively. Solicited injection site reactions including erythema, pain and swelling occurred in 18%, 10% and 4% of subjects, respectively. Four children (8%) had fever (⩾37.7Celsius). Eight children (16%) had adverse events, which were not related to the vaccine. AJE-CV booster dose is highly immunogenic and safe among children who previously received SA14-14-2 vaccine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Multicenter Evaluation of BioFire FilmArray Meningitis/Encephalitis Panel for Detection of Bacteria, Viruses, and Yeast in Cerebrospinal Fluid Specimens.

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    Leber, Amy L; Everhart, Kathy; Balada-Llasat, Joan-Miquel; Cullison, Jillian; Daly, Judy; Holt, Sarah; Lephart, Paul; Salimnia, Hossein; Schreckenberger, Paul C; DesJarlais, Sharon; Reed, Sharon L; Chapin, Kimberle C; LeBlanc, Lindsay; Johnson, J Kristie; Soliven, Nicole L; Carroll, Karen C; Miller, Jo-Anne; Dien Bard, Jennifer; Mestas, Javier; Bankowski, Matthew; Enomoto, Tori; Hemmert, Andrew C; Bourzac, Kevin M

    2016-09-01

    Rapid diagnosis and treatment of infectious meningitis and encephalitis are critical to minimize morbidity and mortality. Comprehensive testing of cerebrospinal fluid (CSF) often includes Gram stain, culture, antigen detection, and molecular methods, paired with chemical and cellular analyses. These methods may lack sensitivity or specificity, can take several days, and require significant volume for complete analysis. The FilmArray Meningitis/Encephalitis (ME) Panel is a multiplexed in vitro diagnostic test for the simultaneous, rapid (∼1-h) detection of 14 pathogens directly from CSF specimens: Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus agalactiae, cytomegalovirus, enterovirus, herpes simplex virus 1 and 2, human herpesvirus 6, human parechovirus, varicella-zoster virus, and Cryptococcus neoformans/Cryptococcus gattii We describe a multicenter evaluation of 1,560 prospectively collected CSF specimens with performance compared to culture (bacterial analytes) and PCR (all other analytes). The FilmArray ME Panel demonstrated a sensitivity or positive percentage of agreement of 100% for 9 of 14 analytes. Enterovirus and human herpesvirus type 6 had agreements of 95.7% and 85.7%, and L. monocytogenes and N. meningitidis were not observed in the study. For S. agalactiae, there was a single false-positive and false-negative result each, for a sensitivity and specificity of 0 and 99.9%, respectively. The specificity or negative percentage of agreement was 99.2% or greater for all other analytes. The FilmArray ME Panel is a sensitive and specific test to aid in diagnosis of ME. With use of this comprehensive and rapid test, improved patient outcomes and antimicrobial stewardship are anticipated. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  12. Encefalitis aguda: Manifestaciones neuropsiquiátricas como expresión de infección por virus de influenza Acute encephalitis: Neuropsychiatric manifestations as expression of influenza virus infection

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    Noris Moreno-Flagge

    2009-01-01

    Full Text Available El objetivo fue revisar la encefalitis en niños y adolescentes, su etiología, manifestaciones clínicas, fisiopatología, métodos diagnósticos y tratamiento, enfatizando las manifestaciones neuropsiquiátricas de la encefalitis durante una epidemia de influenza. La encefalitis se considera una inflamación del sistema nervioso central (SNC que compromete el cerebro. Se manifiesta usualmente por cefaleas, fiebre y trastorno del estado de conciencia. Puede además manifestarse por convulsiones, cambios en la personalidad y manifestaciones obsesivas (síntomas neuropsiquiátricos. Las manifestaciones dependerán del tipo de virus y las células afectadas. La encefalitis puede ser causada por una gran variedad de agentes infecciosos incluyendo virus, bacterias, hongos y parásitos. Causas virales de encefalitis incluyen herpesvirus, arbovirus, rabia y enterovirus. Casos establecidos de bacterias incluyen Borrelia burgdorferi y rickettsia y el Mycoplasma neumoniae, al cual se atribuyen varios casos de encefalitis. Otros agentes como el hongo Coccidioides immitis e Histoplasma capsulatum pueden también generarla. Más de 100 agentes se han asociado a encefalitis. El diagnóstico de encefalitis constituye un reto para el clínico, y su etiología infecciosa usualmente se identifica entre el 40% al 70% de casos. El diagnóstico se hace con absoluta certeza sólo con una biopsia cerebral. La epidemiología depende de ciertos factores como la edad, la localización geográfica, la época del año, las condiciones climáticas y la inmunocompetencia del huésped. El tratamiento temprano puede disminuir el riesgo de muerte y las secuelas. Describimos cuatro pacientes con encefalitis y manifestaciones neuropsiquiátricas durante una epidemia de influenza, con el fin de alertar sobre esta asociación.The aim is to review the encephalitis in infants and adolescents as well as its etiology, clinical manifestation, epidemiology, physiopathology, diagnostic

  13. Inhibition of ERK and proliferation in NK cell lines by soluble HLA-E released from Japanese encephalitis virus infected cells.

    Science.gov (United States)

    Shwetank; Date, Onkar Sanjay; Carbone, Ennio; Manjunath, Ramanathapuram

    2014-11-01

    Productive infection of human endothelial cells with Japanese encephalitis virus (JEV), a single stranded RNA virus induces shedding of sHLA-E. We show here that sHLA-E that is released upon infection with this flavivirus can inhibit IL-2 and PMA mediated ERK 1/2 phosphorylation in two NK cell lines, Nishi and NKL. Virus infected or IFN-γ treated cell culture supernatants containing sHLA-E were found to partially inhibit IL-2 mediated induction of CD25 molecules on NKL cells. It was also found that sHLA-E could inhibit IL-2 induced [(3)H]-thymidine incorporation suggesting that, similar to cell surface expressed HLA-E, sHLA-E could also inhibit NK cell responses. Hence JEV-induced shedding of sHLA-E needs further investigation to better understand immune responses in JEV infections since it may have a role in viral evasion of NK cell responses. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. A single mutation in the Japanese encephalitis virus E protein (S123R) increases its growth rate in mouse neuroblastoma cells and its pathogenicity in mice.

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    Tajima, Shigeru; Nerome, Reiko; Nukui, Yoko; Kato, Fumihiro; Takasaki, Tomohiko; Kurane, Ichiro

    2010-01-20

    We previously reported that the Japanese encephalitis virus (JEV) strain Mie/41/2002 has weak pathogenicity compared with the laboratory strain Beijing-1. To identify the determinants of its growth nature and pathogenicity, we produced intertypic viruses, rJEV(EB1-M41), rJEV(nEB1-M41) and rJEV(cEB1-M41), which contained the entire, the N-terminal, and the C-terminal half, respectively, of the Beijing-1 E region in the Mie/41/2002 background. The growth of rJEV(EB1-M41) in mouse neuroblastoma N18 cells and virulence in mice were similar to those of Beijing-1. rJEV(nEB1-M41) propagated in N18 cells to the same extent as did Beijing-1. Furthermore, we produced mutant viruses with single amino acid substitutions in the N-terminal half of the Mie/41/2002 E region. A Ser-123-Arg mutation in the Mie/41/2002 E protein exhibited significantly increased growth rate in N18 cells and virulence in mice. These results indicate that the position 123 in the E protein is responsible for determining the growth properties and pathogenicity of JEV.

  15. In vitro and in vivo characterization of chimeric duck Tembusu virus based on Japanese encephalitis live vaccine strain SA14-14-2.

    Science.gov (United States)

    Wang, Hong-Jiang; Liu, Long; Li, Xiao-Feng; Ye, Qing; Deng, Yong-Qiang; Qin, E-De; Qin, Cheng-Feng

    2016-07-01

    Duck Tembusu virus (DTMUV), a newly identified flavivirus, has rapidly spread to China, Malaysia and Thailand. The potential threats to public health have been well-highlighted; however its virulence and pathogenesis remain largely unknown. Here, by using reverse genetics, a recombinant chimeric DTMUV based on Japanese encephalitis live vaccine strain SA14-14-2 was obtained by substituting the corresponding prM and E genes (named ChinDTMUV). In vitro characterization demonstrated that ChinDTMUV replicated efficiently in mammalian cells with small-plaque phenotype in comparison with its parental viruses. Mouse tests showed ChinDTMUV exhibited avirulent phenotype in terms of neuroinvasiveness, while it retained neurovirulence from its parental virus DTMUV. Furthermore, immunization with ChinDTMUV was evidenced to elicit robust IgG and neutralizing antibody responses in mice. Overall, we successfully developed a viable chimeric DTMUV, and these results provide a useful platform for further investigation of the pathogenesis of DTMUV and development of a live attenuated DTMUV vaccine candidate.

  16. The Molecular Epidemiology and Evolution of Murray Valley Encephalitis Virus: Recent Emergence of Distinct Sub-lineages of the Dominant Genotype 1.

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    David T Williams

    2015-11-01

    Full Text Available Recent increased activity of the mosquito-borne Murray Valley encephalitis virus (MVEV in Australia has renewed concerns regarding its potential to spread and cause disease.To better understand the genetic relationships between earlier and more recent circulating strains, patterns of virus movement, as well as the molecular basis of MVEV evolution, complete pre-membrane (prM and Envelope (Env genes were sequenced from sixty-six MVEV strains from different regions of the Australasian region, isolated over a sixty year period (1951-2011. Phylogenetic analyses indicated that, of the four recognized genotypes, only G1 and G2 are contemporary. G1 viruses were dominant over the sampling period and found across the known geographic range of MVEV. Two distinct sub-lineages of G1 were observed (1A and 1B. Although G1B strains have been isolated from across mainland Australia, Australian G1A strains have not been detected outside northwest Australia. Similarly, G2 is comprised of only Western Australian isolates from mosquitoes, suggesting G1B and G2 viruses have geographic or ecological restrictions. No evidence of recombination was found and a single amino acid substitution in the Env protein (S332G was found to be under positive selection, while several others were found to be under directional evolution. Evolutionary analyses indicated that extant genotypes of MVEV began to diverge from a common ancestor approximately 200 years ago. G2 was the first genotype to diverge, followed by G3 and G4, and finally G1, from which subtypes G1A and G1B diverged between 1964 and 1994.The results of this study provides new insights into the genetic diversity and evolution of MVEV. The demonstration of co-circulation of all contemporary genetic lineages of MVEV in northwestern Australia, supports the contention that this region is the enzootic focus for this virus.

  17. Anti Japanese encephalitis virus IgM positivity among patients with acute encephalitic syndrome admitted to different hospitals from all over Nepal.

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    Bhattarai, Anupama; Pant, Narayan Dutt; Nepal, Krishus; Adhikari, Sailaja; Sharma, Mukunda; Parajuli, Pramila

    2017-01-01

    The Japanese encephalitis virus (JEV) infection is one of the major public health problems in Nepal because of its increasing disease morbidity and mortality. The main purpose of this study was to determine the anti-JEV IgM positivity among acute encephalitis syndromic cases from all over Nepal. The present study was conducted at National Public Health Laboratory, Kathmandu, Nepal from April 2015 to October 2015. A total of 671 (418 CSF and 253 serum) samples were collected from 625 patients with acute encephalitic syndrome, admitted to different hospitals from all over Nepal. IgM antibody capture enzyme linked immunosorbent assay (ELISA) was used for the detection of anti-JEV IgM positive cases. The rate of anti-JEV IgM positivity was found to be 21.12%. The majority of positive cases (50%) were from the age group below 15 years, with the highest numbers of cases occurring in September (55.30%). Among all the anti-JEV IgM positive cases, higher numbers of cases were males. Geographically, the highest numbers of anti-JEV IgM positive cases were recorded from Terai region. Similarly, largest numbers of anti-JEV IgM positive cases were reported from Kailai district followed by those from Kanchanpur. However, anti-JEV IgM positive cases were also reported from hill districts. Continuation of active surveillance and vector control measures, proper management of diagnostic facilities and expanded program of immunization in JE endemic areas should be strongly emphasized to reduce the endemicity of the disease.

  18. Development and application of a reverse transcriptase droplet digital PCR (RT-ddPCR) for sensitive and rapid detection of Japanese encephalitis virus.

    Science.gov (United States)

    Wu, Xulong; Lin, Hua; Chen, Shijie; Xiao, Lu; Yang, Miao; An, Wei; Wang, Yin; Yao, Xueping; Yang, Zexiao

    2017-10-01

    Japanese encephalitis (JE) is one of the most common zoonoses caused by Japanese encephalitis virus (JEV). Droplet digital PCR (ddPCR) is a novel sensitive, accurate method that enables absolute quantitation without the need for calibration curves. The aim of this study was to develop a RT-ddPCR method to detect JEV, and to compare its sensitivity with real-time TaqMan RT-PCR by analysis of clinical samples. The methods of JEV real-time RT-PCR and RT-ddPCR were established and optimal reaction conditions were confirmed. Each method was evaluated for linearity, limit of detection and specificity. A total of 103 porcine samples were analysed by both methods and the detection rate was calculated. Both methods showed a high degree of linearity and positive correlation for standards (R(2)≥0.999). The assays indicated that the detection limit for RT-ddPCR was approximately 2 copies/20μL well, a 100-fold greater sensitivity than TaqMan real-time RT-PCR. The detection results for clinical samples showed that the positive detection rate of RT-ddPCR (27.2%) was higher than that of TaqMan real-time RT-PCR (16.5%). The cross-reaction was performed with other porcine pathogens, and negative amplification of the cross-reaction assay demonstrated the high specificity of this method. The novel JEV RT-ddPCR assay could be used as an efficient molecular biology tool to diagnose JEV, which would facilitate the surveillance of reproductive failure disease in swineries and would be beneficial for public health security. Copyright © 2017. Published by Elsevier B.V.

  19. Prevalence and genotyping of tick-borne encephalitis virus in questing Ixodes ricinus ticks in a new endemic area in western Switzerland.

    Science.gov (United States)

    Lommano, E; Burri, C; Maeder, G; Guerne, M; Bastic, V; Patalas, E; Gern, L

    2012-01-01

    Tick-borne encephalitis virus (TBEV) is the causative agent of tick-borne encephalitis (TBE) and causes neurological disease in humans in Eurasia. TBEV is transmitted by ticks of the genus Ixodes. Currently 10,000-12,000 clinical cases are reported annually in approximately 30 TBE endemic countries. Since 1990 the epidemiology of TBE is characterized by a global increase of clinical cases and an expansion of risk areas. Similar trends are also observed in Switzerland but few studies confirmed the emergence of new TBE foci by detecting viral RNA in field-collected ticks. In this study, free-living Ixodes ricinus (L.) ticks from one nonendemic and three new TBE endemic regions located in the Western part of Switzerland were screened during four consecutive years (2007-2010) for the presence of TBEV. A total of 9,868 I. ricinus ticks (6,665 nymphs and 3,203 adults) were examined in pools for TBEV by real-time reverse transcription polymerase chain reaction. Our results confirmed the presence of viral RNA in 0.1% (6/6120) of questing ticks collected in one new endemic region. Among TBE endemic sites, the minimal infection rate per 100 ticks tested ranged from 0.21 (1/477) to 0.95 (1/105). Four positive samples were sequenced and phylogenetic analysis of the NS5 gene showed that all TBEV nucleotide sequences belonged to the European subtype and were split into two distinct lineages originating probably independently from two distinct foci located North-East and East of the study region.

  20. Induction of Multiple miR-200/182 Members in the Brains of Mice Are Associated with Acute Herpes Simplex Virus 1 Encephalitis.

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    Anna Majer

    Full Text Available Important roles of microRNAs (miRNAs in regulating the host response during viral infection have begun to be defined. However, little is known about the functional roles of miRNAs within an in vivo acute viral encephalitis model. We therefore identified global changes in miRNA expression during acute herpes simplex virus type 1 (HSV-1 encephalitis (HSVE in mice. We found that many of the highly upregulated miRNAs (miR-155, miR-146a and miR-15b detected in HSV-1 infected brain tissue are known regulators of inflammation and innate immunity. We also observed upregulation of 7 members belonging to the related group of miRNAs, the miR-200 family and miR-182 cluster (miR-200/182. Using in situ hybridization, we found that these miRNAs co-localized to regions of the brain with severe HSVE-related pathology and were upregulated in various cell types including neurons. Induction was apparent but not limited to cells in which HSV-1 was detected by immunohistochemistry, suggesting possible roles of these miRNAs in the host response to viral-induced tissue damage. Bioinformatic prediction combined with gene expression profiling revealed that the induced miR-200/182 members could regulate the biosynthesis of heparan sulfate proteoglycans. Using luciferase assays, we found that miR-96, miR-141, miR-183 and miR-200c all potentially targeted the syndecan-2 gene (Sdc2, which codes for a cell surface heparan sulfate proteoglycan involved in HSV-1 cellular attachment and entry.

  1. Safety of the Inactivated Japanese Encephalitis Virus Vaccine IXIARO in Children: An Open-label, Randomized, Active-controlled, Phase 3 Study.

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    Dubischar, Katrin L; Kadlecek, Vera; Sablan, Benjamin; Borja-Tabora, Charissa Fay; Gatchalian, Salvacion; Eder-Lingelbach, Susanne; Mueller, Zsuzsanna; Westritschnig, Kerstin

    2017-09-01

    Japanese encephalitis remains a serious health concern in Asian countries and has sporadically affected pediatric travelers. In the present study, we monitored the safety profile of the Japanese encephalitis virus vaccine IXIARO (Valneva Austria GmbH, Vienna, Austria) in a pediatric population. We randomized 1869 children between 2 months and 17 years of age in an age-stratified manner to vaccination with IXIARO or one of the control vaccines, Prevnar (formerly Wyeth Pharmaceuticals Inc., now Pfizer Inc., Kent, United Kingdom) and HAVRIX 720 (GlaxoSmithKline Biologicals, Rixensart, Belgium). Adverse events (AEs) (unsolicited and solicited local and systemic AEs), serious AEs and medically attended AEs were assessed up to day 56 and month 7 after the first dose. Incidences of AEs, serious AEs or medically attended AEs did not differ significantly between the groups in any age stratum. AEs were most frequent in children <1 year of age and decreased with age. AEs of special interest, predefined as AEs associated with potential hypersensitivity/allergy or neurologic disorders up to day 56, were reported in 4.6% (IXIARO) versus 6.3% (Prevnar) in the ≥2 months to <1 year age group and 3.4% (IXIARO) versus 3.3% (HAVRIX) in the ≥1 to <18 years age group. Fever, the most frequent systemic reaction in 23.7% of infants to 3.8% of adolescents, decreased with age and did not differ between groups. The safety profile of IXIARO was comparable to the control vaccines in terms of overall AE rates, serious AEs and medically attended AEs.

  2. Dynamics of Vector-Host Interactions in Avian Communities in Four Eastern Equine Encephalitis Virus Foci in the Northeastern U.S.

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    Goudarz Molaei

    2016-01-01

    Full Text Available Eastern equine encephalitis (EEE virus (Togaviridae, Alphavirus is a highly pathogenic mosquito-borne zoonosis that is responsible for occasional outbreaks of severe disease in humans and equines, resulting in high mortality and neurological impairment in most survivors. In the past, human disease outbreaks in the northeastern U.S. have occurred intermittently with no apparent pattern; however, during the last decade we have witnessed recurring annual emergence where EEE virus activity had been historically rare, and expansion into northern New England where the virus had been previously unknown. In the northeastern U.S., EEE virus is maintained in an enzootic cycle involving the ornithophagic mosquito, Culiseta melanura, and wild passerine (perching birds in freshwater hardwood swamps. However, the identity of key avian species that serve as principal virus reservoir and amplification hosts has not been established. The efficiency with which pathogen transmission occurs within an avian community is largely determined by the relative reservoir competence of each species and by ecological factors that influence contact rates between these avian hosts and mosquito vectors.Contacts between vector mosquitoes and potential avian hosts may be directly quantified by analyzing the blood meal contents of field-collected specimens. We used PCR-based molecular methods and direct sequencing of the mitochondrial cytochrome b gene for profiling of blood meals in Cs. melanura, in an effort to quantify its feeding behavior on specific vertebrate hosts, and to infer epidemiologic implications in four historic EEE virus foci in the northeastern U.S. Avian point count surveys were conducted to determine spatiotemporal host community composition. Of 1,127 blood meals successfully identified to species level, >99% of blood meals were from 65 avian hosts in 27 families and 11 orders, and only seven were from mammalian hosts representing three species. We developed an

  3. Nonstructural Protein 1 of Tick-Borne Encephalitis Virus Induces Oxidative Stress and Activates Antioxidant Defense by the Nrf2/ARE Pathway.

    Science.gov (United States)

    Kuzmenko, Yulia V; Smirnova, Olga A; Ivanov, Alexander V; Starodubova, Elizaveta S; Karpov, Vadim L

    2016-01-01

    Infection with tick-borne encephalitis virus (TBEV) causes pathological changes in the central nervous system. However, the possible redox alterations in the infected cells that can contribute to the virus pathogenicity remain unknown. In the current study we explored the ability of TBEV nonstructural protein 1 (NS1) to induce oxidative stress and activate antioxidant defense via the nuclear factor (erythroid-derived-2)-like 2/antioxidant response element (Nrf2/ARE) pathway. HEK 293T cells were transfected with plasmid encoding NS1 protein, and the production of reactive oxygen species (ROS) was measured using oxidation-sensitive dyes, the activation of the ARE promoter was estimated using a reporter plasmid, and the expression of phase II detoxifying enzymes was quantified by measuring their mRNA levels using RT-qPCR. A high level of ROS production was detected in cells transfected with NS1-expressing plasmid. In addition, this protein activated the promoter with an ARE and upregulated the transcription of ARE-dependent genes that encode phase II enzymes. TBEV NS1 protein both triggers ROS production and activates a defense Nrf2/ARE pathway. These data suggest that a role of redox-mediated processes in TBEV-induced damage of the central nervous system should also be explored. These data can contribute to a better understanding of TBEV pathogenicity, further improvement of TBE treatment, and the development of vaccine candidates against this infection. © 2016 S. Karger AG, Basel.

  4. Gold nanoparticle-based RT-PCR and real-time quantitative RT-PCR assays for detection of Japanese encephalitis virus

    Energy Technology Data Exchange (ETDEWEB)

    Huang, S-H; Tsai, M-H; Lin, C-W [Department of Biotechnology, College of Health Science, Asia University, Wufeng, Taichung, Taiwan (China); Yang, T-C; Chuang, P-H [Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan (China); Tsai, I-S; Lu, H-C [Nanotechnology Research Center, Feng Chia University, Taichung, Taiwan (China); Wan Lei; Lin, Y-J [Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Lai, C-H [Department of Microbiology and Immunology, China Medical University, Taichung, Taiwan (China)], E-mail: cwlin@mail.cmu.edu.tw

    2008-10-08

    Virus isolation and antibody detection are routinely used for diagnosis of Japanese encephalitis virus (JEV) infection, but the low level of transient viremia in some JE patients makes JEV isolation from clinical and surveillance samples very difficult. We describe the use of gold nanoparticle-based RT-PCR and real-time quantitative RT-PCR assays for detection of JEV from its RNA genome. We tested the effect of gold nanoparticles on four different PCR systems, including conventional PCR, reverse-transcription PCR (RT-PCR), and SYBR green real-time PCR and RT-PCR assays for diagnosis in the acute phase of JEV infection. Gold nanoparticles increased the amplification yield of the PCR product and shortened the PCR time compared to the conventional reaction. In addition, nanogold-based real-time RT-PCR showed a linear relationship between Ct and template amount using ten-fold dilutions of JEV. The nanogold-based RT-PCR and real-time quantitative RT-PCR assays were able to detect low levels (1-10 000 copies) of the JEV RNA genomes extracted from culture medium or whole blood, providing early diagnostic tools for the detection of low-level viremia in the acute-phase infection. The assays described here were simple, sensitive, and rapid approaches for detection and quantitation of JEV in tissue cultured samples as well as clinical samples.

  5. Gold nanoparticle-based RT-PCR and real-time quantitative RT-PCR assays for detection of Japanese encephalitis virus

    Science.gov (United States)

    Huang, Su-Hua; Yang, Tsuey-Ching; Tsai, Ming-Hong; Tsai, I.-Shou; Lu, Huang-Chih; Chuang, Pei-Hsin; Wan, Lei; Lin, Ying-Ju; Lai, Chih-Ho; Lin, Cheng-Wen

    2008-10-01

    Virus isolation and antibody detection are routinely used for diagnosis of Japanese encephalitis virus (JEV) infection, but the low level of transient viremia in some JE patients makes JEV isolation from clinical and surveillance samples very difficult. We describe the use of gold nanoparticle-based RT-PCR and real-time quantitative RT-PCR assays for detection of JEV from its RNA genome. We tested the effect of gold nanoparticles on four different PCR systems, including conventional PCR, reverse-transcription PCR (RT-PCR), and SYBR green real-time PCR and RT-PCR assays for diagnosis in the acute phase of JEV infection. Gold nanoparticles increased the amplification yield of the PCR product and shortened the PCR time compared to the conventional reaction. In addition, nanogold-based real-time RT-PCR showed a linear relationship between Ct and template amount using ten-fold dilutions of JEV. The nanogold-based RT-PCR and real-time quantitative RT-PCR assays were able to detect low levels (1-10 000 copies) of the JEV RNA genomes extracted from culture medium or whole blood, providing early diagnostic tools for the detection of low-level viremia in the acute-phase infection. The assays described here were simple, sensitive, and rapid approaches for detection and quantitation of JEV in tissue cultured samples as well as clinical samples.

  6. Host cell selection of Murray Valley encephalitis virus variants altered at an RGD sequence in the envelope protein and in mouse virulence.

    Science.gov (United States)

    Lobigs, M; Usha, R; Nestorowicz, A; Marshall, I D; Weir, R C; Dalgarno, L

    1990-06-01

    We have passaged the prototype strain of Murray Valley encephalitis virus in SW13 (human) cells, sequenced the E and M genes, and examined the virulence of the passaged virus for 21-day-old mice following intracranial and intraperitoneal inoculation. Six independent passage series were carried out: four in the presence of mouse hyperimmune ascitic fluid and two without antibody. Changes were observed in the E protein deduced amino acid sequence for each of the six 10th passage stocks sequenced. Eleven changes were observed in total for the six stocks sequenced; these were at residues 117, 118, 390, 423, and 460. Nine of the changes were nonconservative. Five of the six passaged variants were altered at Asp 390 which is part of an Arg-Gly-Asp (RGD) sequence. This change resulted from adaptation to SW13 cells rather than from antibody selection. The RGD sequence (and residue 423) falls within a region which is highly conserved between flaviviruses and is strongly hydrophilic. All five variants which were altered at Asp 390 were attenuated in 21-day-old mice following i.p. inoculation. We propose that the domain of E encompassing the RGD sequence is an important determinant of flavivirus pathogenicity.

  7. Hemiplegia: An initial manifestation of Japanese encephalitis

    OpenAIRE

    Nalini A; Arunodaya G; Taly A; Swamy H; Vasudev M

    2003-01-01

    A 7-year-old boy from an area endemic to Japanese encephalitis (JE) manifested with acute febrile illness, left hemiplegia and preserved consciousness during the prodromal phase of illness. The child developed features of encephalitis 48 hours after the onset of hemiplegia. IgM MAC ELISA for JE virus revealed high titers in the serum and cerebrospinal fluid suggestive of JE. MRI of the brain showed asymmetrical bilateral thalamic hyperintense lesions on T2 weighted image, considered diagnosti...

  8. Anti-NMDA Receptor Encephalitis and Vaccination

    Directory of Open Access Journals (Sweden)

    Hsiuying Wang

    2017-01-01

    Full Text Available Anti-N-methyl-d-aspartate (Anti-NMDA receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint.

  9. The changing epidemiology of Japanese encephalitis and New data: the implications for New recommendations for Japanese encephalitis vaccine.

    Science.gov (United States)

    Connor, Bradley; Bunn, William B

    2017-01-01

    The epidemiology of Japanese Encephalitis and risk to the traveler has changed and continues to evolve. The spread of Japanese Encephalitis virus into new environments, changes in agricultural practice and animal vectors, climate change, peri-urban growth, changes in international travel to Asia, personal risk factors, mosquito vector free transmission, interactions with other flaviviruses and better information on infections without encephalitis and other factors make Japanese Encephalitis an underappreciated risk. There has also been a change in the incidence of Japanese Encephalitis cases that questions the current travel duration and geographic based recommendations. A safe, effective vaccine (Ixiaro) that may be administered in a short course regimen is now available in the United States without the risks of the previous vaccine. However, the vaccine is significantly underutilized. These changes in the epidemiology and new data on the risks of the Japanese Encephalitis virus require a review of the practice guidelines and expert recommendations that do not reflect the current state of knowledge.

  10. West Nile virus encephalitis in organ transplant recipients: another high-risk group for meningoencephalitis and death.

    Science.gov (United States)

    DeSalvo, Debby; Roy-Chaudhury, Prabir; Peddi, Ram; Merchen, Todd; Konijetti, Krishna; Gupta, Manish; Boardman, Robyn; Rogers, Christin; Buell, Joseph; Hanaway, Michael; Broderick, Joseph; Smith, Roger; Woodle, E Steve

    2004-02-15

    West Nile virus infection has been spreading westward across the continental United States since 1999. Although it often presents as a mild, self-limiting viral illness, it can result in a devastating meningoencephalitis in some patient populations, particularly the elderly. We report in this article on two immunosuppressed transplant patients who developed a severe meningoencephalitis caused by mosquito-borne West Nile virus infection. Suggestions for the prevention, diagnosis, and treatment of West Nile virus infection in this patient population are described.

  11. Dengue encephalitis-A rare manifestation of dengue fever

    OpenAIRE

    Madi, Deepak; Achappa, Basavaprabhu; Ramapuram, John T; Chowta, Nityananda; Laxman, Mridula; Mahalingam, Soundarya

    2014-01-01

    The clinical spectrum of dengue fever ranges from asymptomatic infection to dengue shock syndrome. Dengue is classically considered a non-neurotropic virus. Neurological complications are not commonly seen in dengue. The neurological manifestations seen in dengue are encephalitis, meningitis, encephalopathy, stroke and Guillain-Barré syndrome. Dengue encephalitis is a rare disease. We report an interesting case of dengue encephalitis from Southern India. A 49-year-old gentleman presented with...

  12. Japanese Encephalitis: Frequently Asked Questions

    Science.gov (United States)

    ... the vaccine, what should I do? What is Japanese encephalitis? Japanese encephalitis (JE) is a potentially severe ... cause inflammation of the brain (encephalitis). Where does Japanese encephalitis occur? JE occurs in Asia and parts ...

  13. Are patients with erythema migrans who have leukopenia and/or thrombocytopenia coinfected with Anaplasma phagocytophilum or tick-borne encephalitis virus?

    Directory of Open Access Journals (Sweden)

    Franc Strle

    Full Text Available Lyme borreliosis (LB, tick-borne encephalitis (TBE and human granulocytic anaplasmosis (HGA are endemic in central part of Slovenia. We tested the hypothesis that patients with erythema migrans (EM from this region, who have leukopenia and/or thrombocytopenia (typical findings in HGA and in the initial phase of TBE but not in patients with LB are coinfected with Anaplasma phagocytophilum and/or with TBE virus, i.e. that cytopenia is a result of concomitant HGA or the initial phase of TBE. Comparison of clinical and laboratory findings for 67 patients with EM who disclosed leukopenia/thrombocytopenia with the corresponding results in sex- and age-matched patients with EM and normal blood cell counts revealed no differences. In addition, patients with typical EM and leukopenia and/or thrombocytopenia tested negative for the presence of IgM and IgG antibodies to TBE virus by ELISA as well as for the presence of specific IgG antibodies to A. phagocytophilum antigens by IFA in acute and convalescent serum samples. Thus, none of 67 patients (95% CI: 0 to 5.3% with typical EM (the presence of this skin lesion attests for early Lyme borreliosis and is the evidence for a recent tick bite was found to be coinfected with A. phagocytophilum or had a recent primary infection with TBE virus. The findings in the present study indicate that in Slovenia, and probably in other European countries endemic for LB, TBE and HGA, patients with early LB are rarely coinfected with the other tick-transmitted agents.

  14. miR-146a negatively regulates the induction of proinflammatory cytokines in response to Japanese encephalitis virus infection in microglial cells.

    Science.gov (United States)

    Deng, Minnan; Du, Ganqin; Zhao, Jiegang; Du, Xiaowei

    2017-06-01

    Increasing evidence confirms the involvement of virus infection and miRNA, such as miR-146a, in neuroinflammation-associated epilepsy. In the present study, we investigated the upregulation of miR-146a with RT-qPCR and in situ hybridization methods in a mice infection model of Japanese encephalitis virus (JEV) and in vitro. Subsequently we investigated the involvement of miR-146a in modulating JEV-induced neuroinflammation. It was demonstrated that JEV infection promoted miR-146a production in BALB/c mice brain and in cultured mouse microglial C8-B4 cells, along with pro-inflammatory cytokines, such as IL-1β, IL-6, TNF-α, IFN-β and IFN-α. We also found that miR-146a exerted negative regulatory effects upon IL-1β, IL-6, TNF-α, IFN-β and IFN-α in C8-B4 cells. Accordingly, miR-146a downregulation with a miR-146a inhibitor promoted the upregulation of IL-1β, IL-6, TNF-α, IFN-β and IFN-α, whereas miR-146a upregulation with miR-146a mimics reduced the upregulation of these cytokines. Moreover, miR-146a exerted no regulation upon JEV growth in C8-B4 cells. In conclusion, JEV infection upregulated miR-146a and pro-inflammatory cytokine production, in mice brain and in cultured C8-B4 cells. Furthermore, miR-146a negatively regulated the production of JEV-induced pro-inflammatory cytokines, in virus growth independent fashion, identifying miR-146a as a negative feedback regulator in JEV-induced neuroinflammation, and possibly in epilepsy.

  15. Recent advances in the development of vaccines for Ebola virus disease.

    Science.gov (United States)

    Ohimain, Elijah Ige

    2016-01-04

    Ebola virus is one of the most dangerous microorganisms in the world causing hemorrhagic fevers in humans and non-human primates. Ebola virus (EBOV) is a zoonotic infection, which emerges and re-emerges in human populations. The 2014 outbreak was caused by the Zaire strain, which has a kill rate of up to 90%, though 40% was recorded in the current outbreak. The 2014 outbreak is larger than all 20 outbreaks that have occurred since 1976, when the virus was first discovered. It is the first time that the virus was sustained in urban centers and spread beyond Africa into Europe and USA. Thus far, over 22,000 cases have been reported with about 50% mortality in one year. There are currently no approved therapeutics and preventive vaccines against Ebola virus disease (EVD). Responding to the devastating effe1cts of the 2014 outbreak and the potential risk of global spread, has spurred research for the development of therapeutics and vaccines. This review is therefore aimed at presenting the progress of vaccine development. Results showed that conventional inactivated vaccines produced from EBOV by heat, formalin or gamma irradiation appear to be ineffective. However, novel vaccines production techniques have emerged leading to the production of candidate vaccines that have been demonstrated to be effective in preclinical trials using small animal and non-human primates (NHP) models. Some of the promising vaccines have undergone phase 1 clinical trials, which demonstrated their safety and immunogenicity. Many of the candidate vaccines are vector based such as Vesicular Stomatitis Virus (VSV), Rabies Virus (RABV), Adenovirus (Ad), Modified Vaccinia Ankara (MVA), Cytomegalovirus (CMV), human parainfluenza virus type 3 (HPIV3) and Venezuelan Equine Encephalitis Virus (VEEV). Other platforms include virus like particle (VLP), DNA and subunit vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Combined prime-boost vaccination against tick-borne encephalitis (TBE using a recombinant vaccinia virus and a bacterial plasmid both expressing TBE virus non-structural NS1 protein

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    Zakharova LG

    2005-08-01

    Full Text Available Abstract Background Heterologous prime-boost immunization protocols using different gene expression systems have proven to be successful tools in protecting against various diseases in experimental animal models. The main reason for using this approach is to exploit the ability of expression cassettes to prime or boost the immune system in different ways during vaccination procedures. The purpose of the project was to study the ability of recombinant vaccinia virus (VV and bacterial plasmid, both carrying the NS1 gene from tick-borne encephalitis (TBE virus under the control of different promoters, to protect mice against lethal challenge using a heterologous prime-boost vaccination protocol. Results The heterologous prime-boost vaccination protocol, using a VV recombinant and bacterial plasmid, both containing the NS1 TBE virus protein gene under the control of different promoters, achieved a high level of protection in mice against lethal challenge with a highly pathogenic TBE virus strain. No signs of pronounced TBE infection were detected in the surviving animals. Conclusion Heterologous prime-boost vaccination protocols using recombinant VV and bacterial plasmids could be used for the development of flavivirus vaccines.

  17. Ixodes scapularis and Ixodes ricinus tick cell lines respond to infection with tick-borne encephalitis virus: transcriptomic and proteomic analysis.

    Science.gov (United States)

    Weisheit, Sabine; Villar, Margarita; Tykalová, Hana; Popara, Marina; Loecherbach, Julia; Watson, Mick; Růžek, Daniel; Grubhoffer, Libor; de la Fuente, José; Fazakerley, John K; Bell-Sakyi, Lesley

    2015-11-18

    Ixodid ticks are important vectors of a wide variety of viral, bacterial and protozoan pathogens of medical and veterinary importance. Although several studies have elucidated tick responses to bacteria, little is known about the tick response to viruses. To gain insight into the response of tick cells to flavivirus infection, the transcriptomes and proteomes of two Ixodes spp cell lines infected with the flavivirus tick-borne encephalitis virus (TBEV) were analysed. RNA and proteins were isolated from the Ixodes scapularis-derived cell line IDE8 and the Ixodes ricinus-derived cell line IRE/CTVM19, mock-infected or infected with TBEV, on day 2 post-infection (p.i.) when virus production was increasing, and on day 6 p.i. when virus production was decreasing. RNA-Seq and mass spectrometric technologies were used to identify changes in abundance of, respectively, transcripts and proteins. Functional analyses were conducted on selected transcripts using RNA interference (RNAi) for gene knockdown in tick cells infected with the closely-related but less pathogenic flavivirus Langat virus (LGTV). Differential expression analysis using DESeq resulted in totals of 43 and 83 statistically significantly differentially-expressed transcripts in IDE8 and IRE/CTVM19 cells, respectively. Mass spectrometry detected 76 and 129 statistically significantly differentially-represented proteins in IDE8 and IRE/CTVM19 cells, respectively. Differentially-expressed transcripts and differentially-represented proteins included some that may be involved in innate immune and cell stress responses. Knockdown of the heat-shock proteins HSP90, HSP70 and gp96, the complement-associated protein Factor H and the protease trypsin resulted in increased LGTV replication and production in at least one tick cell line, indicating a possible antiviral role for these proteins. Knockdown of RNAi-associated proteins Argonaute and Dicer, which were included as positive controls, also resulted in increased LGTV

  18. The ecology and epidemiology of Ross River and Murray Valley encephalitis viruses in Western Australia: examples of One Health in Action.

    Science.gov (United States)

    Mackenzie, John S; Lindsay, Michael D A; Smith, David W; Imrie, Allison

    2017-06-01

    Arboviruses are maintained and transmitted through an alternating biological cycle in arthropods and vertebrates, with largely incidental disease in humans and animals. As such, they provide excellent examples of One Health, as their health impact is inextricably linked to their vertebrate hosts, their arthropod vectors and the environment. Prevention and control requires a comprehensive understanding of these interactions, and how they may be effectively and safely modified. This review concentrates on human disease due to Ross River and Murray Valley encephalitis viruses, the two major arboviral pathogens in Australia. It describes how their pattern of infection and disease is influenced by natural climatic and weather patterns, and by anthropogenic activities. The latter includes human-mediated environmental manipulations, such as water impoundment infrastructures, human movements and migration, and community and social changes, such as urban spread into mosquito larval habitats. Effective interventions need to be directed at the environmental precursors of risk. This can best be achieved using One Health approaches to improve collaboration and coordination between different disciplines and cross-sectoral jurisdictions in order to develop more holistic mitigation and control procedures, and to address poorly understood ecological issues through multidisciplinary research. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

  19. THE CYTOKINES SYNTHESIS IN VITRO IN THE TICK-BORNE ENCEPHALITIS VIRUS INFECTED CELLS AND IN THE PRESENCE OF INACTIVATED VACCINE

    Directory of Open Access Journals (Sweden)

    M. V. Mesentseva

    2014-01-01

    Full Text Available Abstract. Tick-borne encephalitis (TBE is severe neuroinfectious disease with involvement of immune mechanisms in pathogenesis. Comparative analysis of synthesis of key cytokines had been performed for the TBE virus (TBEV infected cells and in the presence of inactivated vaccine against TBE in vitro. Persistent TBEV infection of immortal tissue culture of human larynx cancer cells caused transcription activation of interferons IFNα, IFNγ, IFNλ1, interleukins IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12, tumour necrosis factor TNFα as well as one of apoptosis factors Fas. Comparison of transcription and production of cytokines revealed that the TBEV infection resulted in posttranscription Th1 shift of cytokine response. In the presence of inactivated vaccine against TBE based on the same strain Sofjin of the TBEV activation of transcription of cytokines IFNα, IFNλ1, IL-4, IL-10 was also observed as after the TBEV infection that together with an additional stimulation of GM-CSF production might serve as an evidence of Th2 response. Involvement of IFNIII type (IFNλ1 both during persistent infection and after addition of inactivated vaccines was found in the first time. Differences in dynamics of cytokines IL-2, IL-8, IL-10, IL-12, TNFα response during the TBEV infection and in the presence of inactivated vaccine are described.

  20. Diagnosis of Herpes Simplex Encephalitis by ELISA Using Antipeptide Antibodies Against Type-Common Epitopes of Glycoprotein B of Herpes Simplex Viruses.

    Science.gov (United States)

    Bhullar, Shradha S; Chandak, Nitin H; Baheti, Neeraj N; Purohit, Hemant J; Taori, Girdhar M; Daginawala, Hatim F; Kashyap, Rajpal S

    2016-01-01

    Herpes simplex encephalitis (HSE) represents one of the most severe infectious diseases of the central nervous system (CNS). As effective antiviral drugs are available, an early, rapid, and reliable diagnosis has become important. The objective of this article was to develop a sensitive ELISA protocol for herpes simplex viruses (HSV) antigen detection and quantitation by assessing the usefulness of antipeptide antibodies against potential peptides of HSV glycoprotein B (gB). A total of 180 cerebrospinal fluid (CSF) samples of HSE and non-HSE patients were analyzed using a panel of antipeptide antibodies against synthetic peptides of HSV glycoprotein gB. The cases of confirmed and suspected HSE showed 80% and 51% positivity for antipeptide against synthetic peptide QLHDLRF and 77% and 53% positivity for antipeptide against synthetic peptide MKALYPLTT, respectively for the detection of HSV antigen in CSF. The concentration of HSV antigen was found to be higher in confirmed HSE as compared to suspected HSE group and the viral load correlated well with antigen concentration obtained using the two antipeptides in CSF of confirmed HSE group. This is the first article describing the use of antibodies obtained against synthetic peptides derived from HSV in diagnostics of HSE using patients' CSF samples.

  1. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH interaction with 3' ends of Japanese encephalitis virus RNA and colocalization with the viral NS5 protein

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    Chou Shih-Jie

    2009-04-01

    Full Text Available Abstract Replication of the Japanese encephalitis virus (JEV genome depends on host factors for successfully completing their life cycles; to do this, host factors have been recruited and/or relocated to the site of viral replication. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH, a cellular metabolic protein, was found to colocalize with viral RNA-dependent RNA polymerase (NS5 in JEV-infected cells. Subcellular fractionation further indicated that GAPDH remained relatively constant in the cytosol, while increasing at 12 to 24 hours postinfection (hpi and decreasing at 36 hpi in the nuclear fraction of infected cells. In contrast, the redistribution patterns of GAPDH were not observed in the uninfected cells. Co-immunoprecipitation of GAPDH and JEV NS5 protein revealed no direct protein-protein interaction; instead, GAPDH binds to the 3' termini of plus- and minus-strand RNAs of JEV by electrophoretic mobility shift assays. Accordingly, GAPDH binds to the minus strand more efficiently than to the plus strand of JEV RNAs. This study highlights the findings that infection of JEV changes subcellular localization of GAPDH suggesting that this metabolic enzyme may play a role in JEV replication.

  2. Roles of TLR3 and RIG-I in Mediating the Inflammatory Response in Mouse Microglia following Japanese Encephalitis Virus Infection

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    Rong Jiang

    2014-01-01

    Full Text Available Japanese encephalitis virus (JEV infection can cause central nervous system disease with irreversible neurological damage in humans and animals. Evidence suggests that overactivation of microglia leads to greatly increased neuronal damage during JEV infection. However, the mechanism by which JEV induces the activation of microglia remains unclear. Toll-like receptor 3 (TLR3 and retinoic acid-inducible gene I (RIG-I can recognize double-stranded RNA, and their downstream signaling results in production of proinflammatory mediators. In this study, we investigated the roles of TLR3 and RIG-I in the inflammatory response caused by JEV infection in the mouse microglial cell line. JEV infection induced the expression of TLR3 and RIG-I and the activation of extracellular signal-regulated kinase (ERK and p38 mitogen-activated protein kinase (p38MAPK. Knockdown of TLR3 and RIG-I attenuated activation of ERK, p38MAPK, activator protein 1 (AP-1, and nuclear factor κB (NF-κB. Secretion of TNF-α, IL-6, and CCL-2, which was induced by JEV, was reduced by TLR3 and RIG-I knockdown and inhibitors of phosphorylated ERK and p38MAPK. Furthermore, viral proliferation was increased following knockdown of TLR3 and RIG-I. Our findings suggest that the signaling pathways of TLR3 and RIG-I play important roles in the JEV-induced inflammatory response of microglia.

  3. Eastern Equine Encephalitis

    Science.gov (United States)

    ... bite of an infected mosquito. Eastern equine encephalitis (EEE) is a rare illness in humans, and only ... EEEV have no apparent illness. Severe cases of EEE (involving encephalitis, an inflammation of the brain) begin ...

  4. Innate immune mechanisms in Japanese encephalitis virus infection: effect on transcription of pattern recognition receptors in mouse neuronal cells and brain tissue.

    Science.gov (United States)

    Fadnis, Prachi Rahul; Ravi, Vasanthapuram; Desai, Anita; Turtle, Lance; Solomon, Tom

    2013-12-01

    Very little information is available on the role of innate immune mechanisms in Japanese encephalitis virus (JEV) infection. This study was designed to investigate the role of all Pattern Recognition Receptors (PRRs) in JEV infection in a mouse neuronal cell line in comparison to events that occur in vivo, using JEV infected suckling and adult mice. Analysis of mRNA expression was carried out using RT-PCR for detection of PRR genes and their downstream pathway genes, while a PCR array technique was used to examine the complete transcription analysis. Amongst the various innate immune receptors, TLR3 gene exhibited differential expression in JEV-infected Neuro2a, in suckling mice and adult mouse brain cells but not in uninfected control cells. The downstream events of TLR3 were confirmed by increased mRNA expression of IRF3 and interferon-β in JEV-infected Neuro2a cells and suckling mice brain tissue. To confirm the functional significance of this observation, TLR3 gene silencing experiments were carried using specific siRNA in Neuro2a cells. The results revealed a significant enhancement of JEV replication in TLR3 gene silenced JEV-infected Neuro2a cells, thereby suggesting that TLR3 serves a protective role against JEV. The expression levels of other PRRs varied. JEV-infected adult mice showed significant upregulation of TLR2 and MDA5 as compared to JEV-infected suckling mice and Neuro2a cells. In addition, upregulation of Myd88 and IRF7 was also noted in adult mice. These observations, coupled with the fact that adult mice infected with JEV exhibited longer survival rates, suggests that the host antiviral TLR2 response seen in adult mice was eventually countered by the virus by using MDA5 receptor. Our findings suggest that different PRRs appear to be involved in JEV infection in Neuro2a cells and brains of suckling and adult mice.

  5. Serological evidence for Saint Louis encephalitis virus in free-ranging New World monkeys and horses within the upper Paraná River basin region, Southern Brazil

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    Walfrido Kühl Svoboda

    2014-06-01

    Full Text Available Introduction Saint Louis encephalitis virus (SLEV primarily occurs in the Americas and produces disease predominantly in humans. This study investigated the serological presence of SLEV in nonhuman primates and horses from southern Brazil. Methods From June 2004 to December 2005, sera from 133 monkeys (Alouatta caraya, n=43; Sapajus nigritus, n=64; Sapajus cay, n=26 trap-captured at the Paraná River basin region and 23 blood samples from farm horses were obtained and used for the serological detection of a panel of 19 arboviruses. All samples were analyzed in a hemagglutination inhibition (HI assay; positive monkey samples were confirmed in a mouse neutralization test (MNT. Additionally, all blood samples were inoculated into C6/36 cell culture for viral isolation. Results Positive seroreactivity was only observed for SLEV. A prevalence of SLEV antibodies in sera was detected in Alouatta caraya (11.6%; 5/43, Sapajus nigritus (12.5%; 8/64, and S. cay (30.8%; 8/26 monkeys with the HI assay. Of the monkeys, 2.3% (1/42 of A. caraya, 6.3% 94/64 of S. nigritus, and 15.4% (4/26 of S. cay were positive for SLEV in the MNT. Additionally, SLEV antibodies were detected by HI in 39.1% (9/23 of the horses evaluated in this study. Arboviruses were not isolated from any blood sample. Conclusions These results confirmed the presence of SLEV in nonhuman primates and horses from southern Brazil. These findings most likely represent the first detection of this virus in nonhuman primates beyond the Amazon region. The detection of SLEV in animals within a geographical region distant from the Amazon basin suggests that there may be widespread and undiagnosed dissemination of this disease in Brazil.

  6. Identification of bloodmeals in Anopheles quadrimaculatus and Anopheles punctipennis from eastern equine encephalitis virus foci in northeastern U.S.A.

    Science.gov (United States)

    Molaei, G; Farajollahi, A; Armstrong, P M; Oliver, J; Howard, J J; Andreadis, T G

    2009-12-01

    The host-feeding patterns of Anopheles quadrimaculatus Say and Anopheles punctipennis (Say) were examined in order to evaluate their potential contributions to the transmission of eastern equine encephalitis virus (EEEv) and other arboviruses in the northeastern U.S.A. Engorged mosquitoes of the two species were collected from EEEv foci in central New York (NY) and throughout New Jersey (NJ), and their bloodmeals were identified using a polymerase chain reaction (PCR)-based assay and sequencing portions of the mitochondrial cytochrome b gene. Analysis of 131 An. quadrimaculatus and 107 An. punctipennis from NY revealed that 97.7% and 97.2%, respectively, had acquired blood solely from mammalian hosts. Similarly, examination of 288 An. quadrimaculatus and 127 An. punctipennis from NJ showed 100% and 96.0%, respectively, contained mammalian-derived bloodmeals. Mosquitoes containing mixed bloodmeals from both avian and mammalian hosts were detected in 1.6% of An. quadrimaculatus from NY, and 2.8% and 4.0% of An. punctipennis from NY and NJ, respectively. White-tailed deer (Odocoileus virginianus) constituted the most common vertebrate host for these anopheline mosquitoes, accounting for 85.8-97.7% of all bloodmeals identified. The predominance of white-tailed deer as a source of bloodmeals supports enzootic amplification of deer-associated arboviruses in this region, including Jamestown Canyon, Cache Valley and Potosi viruses. One horse- and two human-derived bloodmeals were also detected in An. quadrimaculatus collected in NJ. Limited avian-derived bloodmeals were detected from mourning dove (Zenaida macroura), sharp-shinned hawk (Accipiter striatus) and house finch (Carpodacus mexicanus), mostly in mixed bloodmeals. Occasional feeding on avian hosts suggests that these mosquitoes may participate as epizootic-epidemic bridge vectors of EEEv from viraemic birds to mammalian hosts of concern, including horses and humans. An isolate of EEEv was recovered from the head

  7. Envelope Protein Mutations L107F and E138K Are Important for Neurovirulence Attenuation for Japanese Encephalitis Virus SA14-14-2 Strain.

    Science.gov (United States)

    Yang, Jian; Yang, Huiqiang; Li, Zhushi; Wang, Wei; Lin, Hua; Liu, Lina; Ni, Qianzhi; Liu, Xinyu; Zeng, Xianwu; Wu, Yonglin; Li, Yuhua

    2017-01-21

    The attenuated Japanese encephalitis virus (JEV) strain SA14-14-2 has been successfully utilized to prevent JEV infection; however, the attenuation determinants have not been fully elucidated. The envelope (E) protein of the attenuated JEV SA14-14-2 strain differs from that of the virulent parental SA14 strain at eight amino acid positions (E107, E138, E176, E177, E264, E279, E315, and E439). Here, we investigated the SA14-14-2-attenuation determinants by mutating E107, E138, E176, E177, and E279 in SA14-14-2 to their status in the parental virulent strain and tested the replication capacity, neurovirulence, neuroinvasiveness, and mortality associated with the mutated viruses in mice, as compared with those of JEV SA14-14-2 and SA14. Our findings indicated that revertant mutations at the E138 or E107 position significantly increased SA14-14-2 virulence, whereas other revertant mutations exhibited significant increases in neurovirulence only when combined with E138, E107, and other mutations. Revertant mutations at all eight positions in the E protein resulted in the highest degree of SA14-14-2 virulence, although this was still lower than that observed in SA14. These results demonstrated the critical role of the viral E protein in controlling JEV virulence and identified the amino acids at the E107 and E138 positions as the key determinants of SA14-14-2 neurovirulence.

  8. Evaluation of chimeric DNA vaccines consisting of premembrane and envelope genes of Japanese encephalitis and dengue viruses as a strategy for reducing induction of dengue virus infection-enhancing antibody response.

    Science.gov (United States)

    Sjatha, Fithriyah; Kuwahara, Miwa; Sudiro, T Mirawati; Kameoka, Masanori; Konishi, Eiji

    2014-02-01

    Neutralizing antibodies induced by dengue virus (DENV) infection show viral infection-enhancing activities at sub-neutralizing doses. On the other hand, preimmunity against Japanese encephalitis virus (JEV), a congener of DENV, does not increase the severity of DENV infection. Several studies have demonstrated that neutralizing epitopes in the genus Flavivirus are mainly located in domain III (DIII) of the envelope (E) protein. In this study, chimeric premembrane and envelope (prM-E) gene-based expression plasmids of JEV and DENV1 with DIII substitution of each virus were constructed for use as DNA vaccines and their immunogenicity evaluated. Sera from C3H/He and ICR mice immunized with a chimeric gene containing DENV1 DIII on a JEV prM-E gene backbone showed high neutralizing antibody titers with less DENV infection-enhancing activity. Our results confirm the applicability of this approach as a new dengue vaccine development strategy. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

  9. Crystal structure of full-length Zika virus NS5 protein reveals a conformation similar to Japanese encephalitis virus NS5

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Anup K.; Cyr, Matthew; Longenecker, Kenton; Tripathi, Rakesh; Sun, Chaohong; Kempf, Dale J. (AbbVie)

    2017-02-21

    The rapid spread of the recentZika virus(ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 ofZika virus(ZIKV-NS5) is critical for ZIKV replication through the 5'-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space groupP21212 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein fromJapanese encephalitis virusand suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.

  10. The C Terminus of the Core β-Ladder Domain in Japanese Encephalitis Virus Nonstructural Protein 1 Is Flexible for Accommodation of Heterologous Epitope Fusion.

    Science.gov (United States)

    Yen, Li-Chen; Liao, Jia-Teh; Lee, Hwei-Jen; Chou, Wei-Yuan; Chen, Chun-Wei; Lin, Yi-Ling; Liao, Ching-Len

    2015-11-11

    NS1 is the only nonstructural protein that enters the lumen of the endoplasmic reticulum (ER), where NS1 is glycosylated, forms a dimer, and is subsequently secreted during flavivirus replication as dimers or hexamers, which appear to be highly immunogenic to the infected host, as protective immunity can be elicited against homologous flavivirus infections. Here, by using a trans-complementation assay, we identified the C-terminal end of NS1 derived from Japanese encephalitis virus (JEV), which was more flexible than other regions in terms of housing foreign epitopes without a significant impact on virus replication. This mapped flexible region is located in the conserved tip of the core β-ladder domain of the multimeric NS1 structure and is also known to contain certain linear epitopes, readily triggering specific antibody responses from the host. Despite becoming attenuated, recombinant JEV with insertion of a neutralizing epitope derived from enterovirus 71 (EV71) into the C-terminal end of NS1 not only could be normally released from infected cells, but also induced dual protective immunity for the host to counteract lethal challenge with either JEV or EV71 in neonatal mice. These results indicated that the secreted multimeric NS1 of flaviviruses may serve as a natural protein carrier to render epitopes of interest more immunogenic in the C terminus of the core β-ladder domain. The positive-sense RNA genomes of mosquito-borne flaviviruses appear to be flexible in terms of accommodating extra insertions of short heterologous antigens into their virus genes. Here, we illustrate that the newly identified C terminus of the core β-ladder domain in NS1 could be readily inserted into entities such as EV71 epitopes, and the resulting NS1-epitope fusion proteins appeared to maintain normal virus replication, secretion ability, and multimeric formation from infected cells. Nonetheless, such an insertion attenuated the recombinant JEV in mice, despite having retained

  11. Diagnostic Algorithm for Encephalitis

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    J Gordon Millichap

    2013-12-01

    Full Text Available Diagnostic algorithm for initial evaluation of encephalitis in children is proposed with a consensus statement from the International Encephalitis Consortium, a committee begun in 2010 to serve as a practical aid to clinicians evaluating patients with suspected encephalitis.

  12. Viral Encephalitis of Unknown Cause: Current Perspective and Recent Advances

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    Peter G. E. Kennedy

    2017-06-01

    Full Text Available Viral encephalitis causes acute inflammation of the brain parenchyma and is a significant cause of human morbidity and mortality. Although Herpes Simplex encephalitis is the most frequent known cause of fatal sporadic encephalitis in humans, an increasingly wide range of viruses and other microbial pathogens are implicated. Up to 60% of cases of presumed viral encephalitis remain unexplained due to the failure of conventional laboratory techniques to detect an infectious agent. High-throughput DNA sequencing technologies have the potential to detect any microbial nucleic acid present in a biological specimen without any prior knowledge of the target sequence. While there remain challenges intrinsic to these technologies, they have great promise in virus discovery in unexplained encephalitis.

  13. A molecularly cloned, live-attenuated japanese encephalitis vaccine SA14-14-2 virus: a conserved single amino acid in the ij Hairpin of the Viral E glycoprotein determines neurovirulence in mice.

    Science.gov (United States)

    Yun, Sang-Im; Song, Byung-Hak; Kim, Jin-Kyoung; Yun, Gil-Nam; Lee, Eun-Young; Li, Long; Kuhn, Richard J; Rossmann, Michael G; Morrey, John D; Lee, Young-Min

    2014-07-01

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes fatal neurological disease in humans, is one of the most important emerging pathogens of public health significance. JEV represents the JE serogroup, which also includes West Nile, Murray Valley encephalitis, and St. Louis encephalitis viruses. Within this serogroup, JEV is a vaccine-preventable pathogen, but the molecular basis of its neurovirulence remains unknown. Here, we constructed an infectious cDNA of the most widely used live-attenuated JE vaccine, SA14-14-2, and rescued from the cDNA a molecularly cloned virus, SA14-14-2MCV, which displayed in vitro growth properties and in vivo attenuation phenotypes identical to those of its parent, SA14-14-2. To elucidate the molecular mechanism of neurovirulence, we selected three independent, highly neurovirulent variants (LD50, 1.5×105 PFU) by serial intracerebral passage in mice. Complete genome sequence comparison revealed a total of eight point mutations, with a common single G1708→A substitution replacing a Gly with Glu at position 244 of the viral E glycoprotein. Using our infectious SA14-14-2 cDNA technology, we showed that this single Gly-to-Glu change at E-244 is sufficient to confer lethal neurovirulence in mice, including rapid development of viral spread and tissue inflammation in the central nervous system. Comprehensive site-directed mutagenesis of E-244, coupled with homology-based structure modeling, demonstrated a novel essential regulatory role in JEV neurovirulence for E-244, within the ij hairpin of the E dimerization domain. In both mouse and human neuronal cells, we further showed that the E-244 mutation altered JEV infectivity in vitro, in direct correlation with the level of neurovirulence in vivo, but had no significant impact on viral RNA replication. Our results provide a crucial step toward developing novel therapeutic and preventive strategies against JEV and possibly other encephalitic flaviviruses.

  14. Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and anti-tumor effects

    Science.gov (United States)

    Osada, Takuya; Berglund, Peter; Morse, Michael A.; Hubby, Bolyn; Lewis, Whitney; Niedzwiecki, Donna; Hobeika, Amy; Burnett, Bruce; Devi, Gayathri R.; Clay, Timothy M.; Smith, Jonathan; Lyerly, H. Kim

    2013-01-01

    We recently demonstrated that Venezuelan equine encephalitis (VEE) virus-based replicon particles (VRP) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP expressing Interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and anti-tumor efficacy. Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)) and VRP-IL-12 was also administered at the same site or at a distant location. CEA-specific T cell and antibody responses were measured. To determine antitumor activity, mice were implanted with MC38-CEA-2 cells and immunized with VRP-CEA with and without VRP-IL-12 and tumor growth and mouse survival were measured. VRP-IL-12 greatly enhanced CEA-specific T cell and antibody responses when combined with VRP-CEA(6D) vaccination. VRP IL-12 was superior to IL-12 protein at enhancing immune responses. Vaccination with VRP-CEA(6D) plus VRP-IL-12 was superior to VRP-CEA(6D) or VRP-IL-12 alone in inducing anti-tumor activity and prolonging survival in tumor-bearing mice. Importantly, local injection of VRP-IL-12 at the VRP-CEA(6D) injection site provided more potent activation of CEA-specific immune responses than VRP-IL-12 injected at a distant site from the VRP-CEA injections. Together, this study shows that VRP-IL-12 enhances vaccination with VRP-CEA(6D) and was more effective at activating CEA-specific T cell responses when locally expressed at the vaccine site. Clinical trials evaluating the adjuvant effect of VRP-IL-12 at enhancing the immunogenicity of cancer vaccines are warranted. PMID:22488274

  15. Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects.

    Science.gov (United States)

    Osada, Takuya; Berglund, Peter; Morse, Michael A; Hubby, Bolyn; Lewis, Whitney; Niedzwiecki, Donna; Yang, Xiao Yi; Hobeika, Amy; Burnett, Bruce; Devi, Gayathri R; Clay, Timothy M; Smith, Jonathan; Kim Lyerly, H

    2012-11-01

    We recently demonstrated that Venezuelan equine encephalitis virus-based replicon particle (VRPs) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP-expressing interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and antitumor efficacy. Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)), and VRP-IL-12 was also administered at the same site or at a distant location. CEA-specific T cell and antibody responses were measured. To determine antitumor activity, mice were implanted with MC38-CEA-2 cells and immunized with VRP-CEA with and without VRP-IL-12, and tumor growth and mouse survival were measured. VRP-IL-12 greatly enhanced CEA-specific T cell and antibody responses when combined with VRP-CEA(6D) vaccination. VRP-IL-12 was superior to IL-12 protein at enhancing immune responses. Vaccination with VRP-CEA(6D) plus VRP-IL-12 was superior to VRP-CEA(6D) or VRP-IL-12 alone in inducing antitumor activity and prolonging survival in tumor-bearing mice. Importantly, local injection of VRP-IL-12 at the VRP-CEA(6D) injection site provided more potent activation of CEA-specific immune responses than that of VRP-IL-12 injected at a distant site from the VRP-CEA injections. Together, this study shows that VRP-IL-12 enhances vaccination with VRP-CEA(6D) and was more effective at activating CEA-specific T cell responses when locally expressed at the vaccine site. Clinical trials evaluating the adjuvant effect of VRP-IL-12 at enhancing the immunogenicity of cancer vaccines are warranted.

  16. Long-term Immunogenicity of a Single Dose of Japanese Encephalitis Chimeric Virus Vaccine in Toddlers and Booster Response 5 Years After Primary Immunization.

    Science.gov (United States)

    Kosalaraksa, Pope; Watanaveeradej, Veerachai; Pancharoen, Chitsanu; Capeding, Maria Rosario; Feroldi, Emmanuel; Bouckenooghe, Alain

    2017-04-01

    Japanese encephalitis (JE) is an important mosquito-borne viral disease that is endemic in Asia, Western Pacific countries and Northern Australia. Although there is no antiviral treatment, vaccination is effective in preventing this disease. We followed a cohort of 596 children for 5 years after primary vaccination at 12-18 months of age with JE chimeric virus vaccine (JE-CV; IMOJEV) in a multicenter, phase III trial in Thailand and the Philippines to assess antibody persistence and safety. At the end of the 5 years, a subgroup of 85 participants, at 1 site in Thailand, was followed after administration of a JE-CV booster vaccination. JE antibody titers were measured annually after primary vaccination and 28 days after booster vaccination using a 50% plaque reduction neutralization test. Seroprotection was defined as a JE-CV neutralizing antibody titer ≥10 (1/dil). Kaplan-Meier survival analysis was used to estimate the proportion of participants maintaining protective JE-CV neutralizing antibody titers. At 1, 2, 3, 4 and 5 years after vaccination with JE-CV, 88.5%, 82.9%, 78.2%, 74.0% and 68.6% of the participants followed remained seroprotected. Geometric mean titers in the subgroup assessed after receipt of a booster dose increased from 61.2 (95% confidence interval: 43.8-85.7) pre-booster to 4951 (95% confidence interval: 3928-6241) 28 days post-booster, with all participants seroprotected. There were no safety concerns identified. Protective immune responses persisted for at least 5 years after a JE-CV primary immunization in the majority of participants. JE-CV booster induced a robust immune response even after a 5-year interval.

  17. Is caprine arthritis encephalitis virus (CAEV) transmitted vertically to early embryo development stages (morulae or blastocyst) via in vitro infected frozen semen?

    Science.gov (United States)

    Al Ahmad, M Z Ali; Chebloune, Y; Chatagnon, G; Pellerin, J L; Fieni, F

    2012-05-01

    The aim of this study was to determine, in vivo, whether in vitro infected cryopreserved caprine sperm is capable of transmitting caprine arthritis-encephalitis virus (CAEV) vertically to early embryo development stages via artificial insemination with in vitro infected semen. Sperm was collected from CAEV-free bucks by electroejaculation. Half of each ejaculate was inoculated with CAEV-pBSCA at a viral concentration of 10(4) TCID(50)/mL. The second half of each ejaculate was used as a negative control. The semen was then frozen. On Day 13 of superovulation treatment, 14 CAEV-free does were inseminated directly into the uterus under endoscopic control with thawed infected semen. Six CAEV-free does, used as a negative control, were inseminated intrauterine with thawed CAEV-free sperm, and eight CAEV-free does were mated with naturally infected bucks. Polymerase chain reaction (PCR) was used to detect CAEV proviral-DNA in the embryos at the D7 stage, in the embryo washing media, and in the uterine secretions of recipient does. At Day 7, all the harvested embryos were PCR-negative for CAEV proviral-DNA; however, CAEV proviral-DNA was detected in 8/14 uterine smears, and 9/14 flushing media taken from does inseminated with infected sperm, and in 1/8 uterine swabs taken from the does mated with infected bucks. The results of this study confirm that (i) artificial insemination with infected semen or mating with infected bucks may result in the transmission of CAEV to the does genital tack seven days after insemination, and (ii) irrespective of the medical status of the semen or the recipient doe, it is possible to obtain CAEV-free early embryos usable for embryo transfer. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. The Involvement of Microglial Cells in Japanese Encephalitis Infections

    Science.gov (United States)

    Thongtan, Thananya; Thepparit, Chutima; Smith, Duncan R.

    2012-01-01

    Despite the availability of effective vaccines, Japanese encephalitis virus (JEV) infections remain a leading cause of encephalitis in many Asian countries. The virus is transmitted to humans by Culex mosquitoes, and, while the majority of human infections are asymptomatic, up to 30% of JE cases admitted to hospital die and 50% of the survivors suffer from neurological sequelae. Microglia are brain-resident macrophages that play key roles in both the innate and adaptive immune responses in the CNS and are thus of importance in determining the pathology of encephalitis as a result of JEV infection. PMID:22919405

  19. Limbic encephalitis, specifically depicted by PET

    NARCIS (Netherlands)

    Bernsen, RA; deJong, BM

    A 44-year-old woman suffered from limbic encephalitis, possibly caused by herpes simplex virus. Neither CT-scanning nor MR-imaging showed a persistent lesion. Positron emission tomography, however, indicated a metabolic deficit in circumscript limbic structures, namely gyrus cinguli and temporal

  20. Improved CT Detection of Acute Herpes Simplex Virus Type 1 Encephalitis Based on a Frequency-Selective Nonlinear Blending: Comparison With MRI.

    Science.gov (United States)

    Bongers, Malte Niklas; Bier, Georg; Ditt, Hendrik; Beck, Robert; Ernemann, Ulrike; Nikolaou, Konstantin; Horger, Marius

    2016-11-01

    The purpose of this study is to compare the diagnostic efficacy of a new CT postprocessing tool based on frequency-selective nonlinear blending (best-contrast CT) with that of standard linear blending of unenhanced head CT in patients with herpes simplex virus type 1 and herpes simplex virus encephalitis (HSE), using FLAIR MRI sequences as the standard of reference. Fifteen consecutive patients (six women and nine men; mean [± SD] age, 60 ± 19 years) with proven HSE (positive polymerase chain reaction results from CSF analysis and the presence of neurologic deficits) were retrospectively enrolled. All patients had undergone head CT and MRI (mean time interval, 2 ± 2 days). After standardized unenhanced head CT scans were read, presets of the best-contrast algorithm were determined (center, 30 HU; delta, 5 HU; slope, 5 nondimensional), and resulting images were analyzed. Contrast enhancement was objectively measured by ROI analysis, comparing contrast-to-noise ratios (CNRs) of unenhanced CT and best-contrast CT. FLAIR and DWI MRI sequences were analyzed, and FLAIR was considered as the standard of reference. For assessment of disease extent, a previously reported 50-point score (HSE score) was used. CNR values for unenhanced head CT (CNR, 5.42 ± 2.77) could be statistically significantly increased using best-contrast CT (CNR, 9.62 ± 4.28) (p = 0.003). FLAIR sequences yielded a median HSE score of 9.0 (range, 6-17) and DWI sequences yielded HSE scores of 6.0 (range, 5-17). By comparison, unenhanced head CT resulted in a median HSE score of 3.5 (range, 1-6). The median best-contrast CT HSE score was 7.5 (range, 6-10). Agreement between FLAIR and unenhanced CT was 54.44%, that between DWI and best-contrast CT was 95.36%, and that between FLAIR and best-contrast CT was 85.21%. The most frequently overseen findings were located at the level of the upper part of the mesencephalon and at the subthalamic or insular level. Frequency-selective nonlinear blending

  1. Etiology and prognosis of acute viral encephalitis and meningitis in Chinese children: a multicentre prospective study.

    Science.gov (United States)

    Ai, Junhong; Xie, Zhengde; Liu, Gang; Chen, Zongbo; Yang, Yong; Li, Yuning; Chen, Jing; Zheng, Guo; Shen, Kunling

    2017-07-14

    In China, there were few studies about the pathogens of acute viral encephalitis and meningitis in children in recent years. The aims of this study were to characterize the etiology and prognosis of acute viral encephalitis and meningitis in Chinese children. This was a multicentre prospective study. Two hundred and sixty one viral encephalitis patients and 285 viral meningitis patients were enrolled. The mean age of viral encephalitis and meningitis were 5.88 ± 3.60 years and 6.39 ± 3.57 years, respectively. Real-time reverse transcription PCR and multiplex PCR were used to detect human enteroviruses and herpes viruses in cerebrospinal fluid (CSF) of patients with encephalitis or meningitis. The enzyme-linked immune absorbent assay (ELISA) was used for detecting IgM antibody against Japanese encephalitis virus (JEV) in CSF and against mumps virus, tick-borne encephalitis virus (TBEV), dengue virus and rubella virus in acute serum. The clinical and outcome data were collected during patients' hospitalization. The etiology of viral encephalitis was confirmed in 52.5% patients. The primary pathogen was human enteroviruses (27.7%) in viral encephalitis. The incidence of sequelae and the fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The etiology of viral meningitis was identified in 42.8% cases. The leading pathogen was also human enteroviruses (37.7%) in viral meningitis. The prognosis of viral meningitis was favorable with only 0.7% patients had neurological sequelae. Human enteroviruses were the leading cause both in acute viral encephalitis and viral meningitis in children. The incidence of sequelae and fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The prognosis of viral meningitis was favorable compared to viral encephalitis.

  2. West Nile and st. Louis encephalitis viruses antibodies surveillance in captive and free-ranging birds of prey from Argentina.

    Science.gov (United States)

    Quaglia, Agustin I; Diaz, Luis A; Argibay, Hernan; Contigiani, Marta S; Saggese, Miguel D

    2014-12-01

    We evaluated the prevalence of WNV and SLEV neutralizing antibodies in captive and free-ranging raptors from Argentina by plaque-reduction neutralization test. Eighty plasma samples from 12 species were analyzed. Only one captive adult Crowned Eagle (Harpyhaliaetus coronatus) was WNV seropositive (prevalence: 1.25%; antibody titer of 1:80). Two captive Crowned Eagles were SLEV seropositive (prevalence: 2.50%; antibody titers: 1:80 and 1:40).These findings expand the geographic distribution of WNV and SLEV and confirm their activity in central and northeastern Argentina. West Nile virus activity in Argentina may represent a potential threat to Crowned Eagles and other endangered raptors in this country.

  3. MRI in tick-borne encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Alkadhi, H.; Kollias, S.S. [Institute of Neuroradiology, University Hospital of Zurich (Switzerland)

    2000-10-01

    The tick-borne encephalitis (TBE) virus gives rise to epidemic encephalitis. Mild forms usually manifest as influenza-like episodes or are clinically silent. MRI is usually normal in TBE. We describe severe TBE in a patient who presented with fever and altered mental status after a tick bite and a specific antibody response to TBE. MRI revealed pronounced signal abnormalities in the basal ganglia and thalamus, without contrast enhancement. These findings coincide well with neuropathological studies of severe nerve cell degeneration with inflammatory cell infiltrates, neuronophagia and reactive astrocytosis in the deep grey matter. We review the literature and discuss the relevant differential diagnosis. (orig.)

  4. Inefficient Mechanical Transmission of Langat (Tick-Borne Encephalitis Virus Complex) Virus by Blood-Feeding Mites (Acari) to Laboratory Mice

    Science.gov (United States)

    1993-05-01

    LGT virus by tick bite has been dem- tropical rat mite, Ornithonyssus bacoti (H-irst), onstrated experimentally for Ixodes ricinus (L.) and the chicken...Thorell in Thailand, Kocianova & Kozuch 1988). Therefo~re, the po- Ixodes granulatus Supino in Malaysia, and Ix- tential for two species of widely

  5. Infecção experimental em cabritos pelo vírus da artrite encefalite Caprine arthritis encephalitis virus experimental infection in new-born kids

    Directory of Open Access Journals (Sweden)

    M.I.M.C. Guedes

    2001-02-01

    Full Text Available Vinte e quatro caprinos de uma semana de idade, soronegativos pela imunodifusão em gel de agar para artrite encefalite caprina (AEC, foram utilizados para estudo de infecção experimental pelo vírus da AEC. Dezesseis animais foram inoculados com lentivirus caprino, amostra Cork, oito pela via intravenosa e oito por instilação nasal. Oito animais serviram como controle, inoculados pelas vias intranasal ou intravenosa com 1ml de meio de cultura de células não infectadas. Os animais foram sacrificados aos 2, 6, 12 e 20 dias pós-inoculação (PI, e colhidas amostras do sistema nervoso central, articulações, tonsilas, linfonodos, pulmões, rins, timo, baço e intestinos delgado e grosso para histopatologia e imunoistoquímica. Um animal inoculado com o vírus da AEC pela via intranasal e sacrificado aos 20 dias PI apresentou imunomarcação positiva em um macrófago alveolar. Concluiu-se que a via aerógena é uma provável rota de infecção pelo vírus da AEC.The caprine arthritis encephalitis virus (CAEV experimental infection was studied in 24 one-week-old seronegative kids. Sixteen kids were inoculated with CAEV-Cork, with 10(6 TCID50/ml concentration, being eight inoculated intravenously, and eight intranasally. Eight animals were used as controls, being four inoculated intravenously, and four intranasally with non-infected cell culture medium. Since the day of the inoculation, clinical evaluation was performed daily, until the day of the sacrifice. Blood samples were taken for serological tests. The animals were killed in pairs at 2, 6, 12 and 20 days post-inoculation (PI and tissues samples of central nervous system, joints, tonsils, lymphonodes, lungs, kidneys, thymus, spleen, small and large intestine were collected for histopathological and immunohistochemical studies. One animal CAEV inoculated intranasally and killed at 20 days PI showed immunohistochemical positive reaction in an alveolar macrophage. It was concluded that

  6. Mycoplasma Pneumoniae Encephalitis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-09-01

    Full Text Available The epidemiological, clinical, laboratory, and imaging findings of patients with M. pneumoniae encephalitis referred to the California Encephalitis Project are reported from the California Department of Health Services, Viral and Rickettsial Disease Laboratory, Richmond, CA, and the Centers for Disease Control and Prevention, Atlanta, GA.

  7. Detection and genetic characterization of tick-borne encephalitis virus (TBEV) derived from ticks removed from red foxes (Vulpes vulpes) and isolated from spleen samples of red deer (Cervus elaphus) in Croatia.

    Science.gov (United States)

    Jemeršić, Lorena; Dežđek, Danko; Brnić, Dragan; Prpić, Jelena; Janicki, Zdravko; Keros, Tomislav; Roić, Besi; Slavica, Alen; Terzić, Svjetlana; Konjević, Dean; Beck, Relja

    2014-02-01

    Tick-borne encephalitis (TBE) is a growing public health concern in central and northern European countries. Even though TBE is a notifiable disease in Croatia, there is a significant lack of information in regard to vector tick identification, distribution as well as TBE virus prevalence in ticks or animals. The aim of our study was to identify and to investigate the viral prevalence of TBE virus in ticks removed from red fox (Vulpes vulpes) carcasses hunted in endemic areas in northern Croatia and to gain a better insight in the role of wild ungulates, especially red deer (Cervus elaphus) in the maintenance of the TBE virus in the natural cycle. We identified 5 tick species (Ixodes ricinus, Ixodes hexagonus, Haemaphysalis punctata, Dermacentor reticulatus, Rhipicephalus sanguineus) removed from 40 red foxes. However, TBE virus was isolated only from adult I. ricinus and I. hexagonus ticks showing a viral prevalence (1.6%) similar to or higher than reported in endemic areas of other European countries. Furthermore, 2 positive spleen samples from 182 red deer (1.1%) were found. Croatian TBE virus isolates were genetically analyzed, and they were shown to be closely related, all belonging to the European TBE virus subgroup. However, on the basis of nucleotide and amino acid sequence analysis, 2 clusters were identified. Our results show that further investigation is needed to understand the clustering of isolates and to identify the most common TBE virus reservoir hosts in Croatia. Sentinel surveys based on wild animal species would give a better insight in defining TBE virus-endemic and possible risk areas in Croatia. Copyright © 2013. Published by Elsevier GmbH.

  8. Encefalitis por virus San Luis en la Ciudad de Buenos Aires durante el brote de dengue 2009 Saint Louis encephalitis virus in Buenos Aires city during the outbreak of dengue in 2009

    Directory of Open Access Journals (Sweden)

    Horacio López

    2011-06-01

    Full Text Available Se presenta un paciente de 80 años de edad, residente en la Ciudad de Buenos Aires, con diagnóstico serológico para el virus de la encefalitis de San Luis (SLE durante el brote de dengue ocurrido entre enero y mayo de 2009. Presentaba leucemia linfoide crónica en tratamiento con clorambucilo, cáncer de próstata tratado con hormonoterapia y radioterapia, e imágenes óseas compatibles con metástasis. El estudio del líquido cefalorraquídeo demostró pleocitosis con predominio de mononucleares y proteinorraquia elevada. El resultado de los cultivos para bacterias, hongos y micobacterias, así como el PCR en LCR para herpes virus, HSV, CMV y EBV, fue negativo. Se detectaron anticuerpos IgM para virus SLE tanto en LCR como en muestra de suero, con seroconversión IgG por neutralización en cultivos celulares y resultados negativos para los demás Flavivirus con circulación en Argentina. Se revisan evidencias sobre la presencia de virus de San Luis en nuestro país, y se señala la importancia de la confirmación diagnóstica y el estudio de otros Flavivirus en casos sospechosos de dengue con presentación grave o atípica. Este trabajo remarca la necesidad de fortalecer tanto la vigilancia epidemiológica del virus SLE, como el control vectorial para prevenir las diferentes infecciones transmitidas por mosquitos y conocer su efecto en Salud Pública en la Argentina.We report the case of a male, 80-year-old resident in the City of Buenos Aires, with a diagnosis of St. Louis encephalitis (SLE during a countrywide dengue outbreak, from January to May 2009. The patient had a chronic lymphocytic leukemia treated with chlorambucil, prostate cancer (hormone therapy and radiotherapy and images consistent with bone metastases. Cerebrospinal fluid examination showed pleocytosis with a predominance of mononuclear cells and high protein concentration. Bacteria, fungi and mycobacteria cultures, as well as the PCR for herpes virus, HSV, CMV and EBV, were

  9. Development of a vaccine to prevent Japanese encephalitis: a brief review

    Science.gov (United States)

    Wiwanitkit, Viroj

    2009-01-01

    Japanese encephalitis (ICD 10: A83.0) is an important specific viral encephalitis caused by the Japanese encephalitis virus, a virus of the Flavivirus group. Millions of people, especially those in endemic areas of developing countries in Asia, are at high risk from this infection. Therefore proper management to deal with this virus is essential. There is no specific treatment for Japanese encephalitis virus. Supportive and symptomatic treatments are usually used, which emphasize the importance of prevention in this specific neurological disorder. Vector control or vaccination can be used to prevent the disease. Because the existing Japanese encephalitis vaccine poses some undesirable problems, a new vaccine is needed. The process of developing a new vaccine is briefly discussed. PMID:20360904

  10. Viral meningitis and encephalitis.

    Science.gov (United States)

    Tuppeny, Misti

    2013-09-01

    Meningitis is an inflammation of the meninges, whereas encephalitis is inflammation of the parenchymal brain tissue. The single distinguishing element between the 2 diagnoses is the altered state of consciousness, focal deficits, and seizures found in encephalitis. Consequently meningoencephalitis is a term used when both findings are present in the patient. Viral meningitis is not necessarily reported as it is often underdiagnosed, whereas encephalitis cases are on the increase in various areas of North America. Improved imaging and viral diagnostics, as well as enhanced neurocritical care management, have improved patient outcomes to date. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Reducing Vulnerability to the Threat of Japanese Encephalitis in ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2016-04-25

    Apr 25, 2016 ... The Japanese encephalitis (JE) virus results in between 30,000 to 50,000 reported cases a year in South and Southeast Asia. Generally, the virus presents mild symptoms in people, but children are especially vulnerable. Acute cases are often fatal as the disease can cause swelling of the brain, tremors, ...

  12. Reducing Vulnerability to the Threat of Japanese Encephalitis in ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    25 avr. 2016 ... The Japanese encephalitis (JE) virus results in between 30,000 to 50,000 reported cases a year in South and Southeast Asia. Generally, the virus presents mild symptoms in people, but children are especially vulnerable. Acute cases are often fatal as the disease can cause swelling of the brain, tremors, ...

  13. Replication of Japanese Encephalitis Virus.

    Science.gov (United States)

    1980-12-10

    division , school, laboratory, etc., of the author. List city, state, and ZIP Code. Block 10 Program Element, Project, Task Area, and Work Unit Numbers...largely of smooth and some rough intracytoplasmic membranes. ....4’ .... ..... . 14 Table 4. Phospholipid distribution in celular membranes and virions

  14. Tick-borne encephalitis: A review of epidemiology, clinical characteristics, and management

    OpenAIRE

    Bogovic, Petra; Strle, Franc

    2015-01-01

    Tick-borne encephalitis is an infection of central nervous system caused by tick-borne encephalitis virus transmitted to humans predominantly by tick bites. During the last few decades the incidence of the disease has been increasing and poses a growing health problem in almost all endemic European and Asian countries. Most cases occur during the highest period of tick activity, in Central Europe mainly from April to November. Tick-borne encephalitis is more common in adults than in children....

  15. Animal intelligence as encephalization.

    Science.gov (United States)

    Jerison, H J

    1985-02-13

    There is no consensus on the nature of animal intelligence despite a century of research, though recent work on cognitive capacities of dolphins and great apes seems to be on one right track. The most precise quantitative analyses have been of relative brain size, or structural encephalization, undertaken to find biological correlates of mind in animals. Encephalization and its evolution are remarkably orderly, and if the idea of intelligence were unknown it would have to be invented to explain encephalization. The scientific question is: what behaviour or dimensions of behaviour evolved when encephalization evolved? The answer: the relatively unusual behaviours that require increased neural information processing capacity, beyond that attributable to differences among species in body size. In this perspective, the different behaviours that depend on augmented processing capacity in different species are evidence of different intelligences (in the plural) that have evolved.

  16. Influenza-Associated Encephalitis

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2002-02-01

    Full Text Available Twenty patients with influenza-associated encephalitis/encephalopathy treated during the 1997-2001 influenza A epidemics in Japan are reported from Niigata City General Hospital, Japan.

  17. Genetic and phenotypic properties of vero cell-adapted Japanese encephalitis virus SA14-14-2 vaccine strain variants and a recombinant clone, which demonstrates attenuation and immunogenicity in mice.

    Science.gov (United States)

    Gromowski, Gregory D; Firestone, Cai-Yen; Bustos-Arriaga, José; Whitehead, Stephen S

    2015-01-01

    The live-attenuated Japanese encephalitis virus (JEV) SA14-14-2 vaccine, produced in primary hamster kidney cells, is safe and effective. Past attempts to adapt this virus to replicate in cells that are more favorable for vaccine production resulted in mutations that significantly reduced immunogenicity. In this study, 10 genetically distinct Vero cell-adapted JEV SA14-14-2 variants were isolated and a recombinant wild-type JEV clone, modified to contain the JEV SA14-14-2 polyprotein amino acid sequence, was recovered in Vero cells. A single capsid protein mutation (S66L) was important for Vero cell-adaptation. Mutations were also identified that modulated virus sensitivity to type I interferon-stimulation in Vero cells. A subset of JEV SA14-14-2 variants and the recombinant clone were evaluated in vivo and exhibited levels of attenuation that varied significantly in suckling mice, but were avirulent and highly immunogenic in weanling mice and are promising candidates for the development of a second-generation, recombinant vaccine. © The American Society of Tropical Medicine and Hygiene.

  18. A possible case of acute disseminated encephalomyelitis after Japanese encephalitis.

    Science.gov (United States)

    Chen, Wei-Liang; Liao, Ming-Feng; Chiang, Han-Lin; Lin, Shinn-Kuang

    2013-12-01

    Acute disseminated encephalomyelitis (ADEM) is a monophasic demyelination disease of central nervous system (CNS) with presentations of impaired consciousness, neurologic deficits and diffuse white matter lesions on magnetic resonance imaging (MRI). Predisposing infection can be identified in around 50 to 77% of all patients with ADEM. Post-infectious autoimmune events associated with Japanese encephalitis have been limited to case reports of Guillain-Barre syndrome after Japanese encephalitis and Japanese encephalitis virus vaccine-related ADEM. We herein report the first possible patient with Japanese encephalitis developed a subsequent ADEM after recovery from Japanese encephalitis. A 50-year-old man suffered from an acute onset of headache, fever, and disturbance of consciousness. Japanese encephalitis was diagnosed by virological and image study. He recovered gradually and was discharged about 1.5 months later. However, another episode of consciousness impairment with violent behavior occurred 21 days after discharge. Acute disseminated encephalomyelitis was confirmed by brain MRI which showed newly developed diffuse white matter lesions. His clinical symptoms and abnormal brain lesions on MRI improved gradually after combination of high-dose intravenous methylprednisolone and oral steroid therapy. Our patient is a possible case of ADEM developing after Japanese encephalitis. High dose steroid therapy resulted in good outcome of ADEM.

  19. An Immunoinformatics-Derived DNA Vaccine Encoding Human Class 2 T Cell Epitopes of Ebola Virus, Sudan Virus, and Venezuelan Equine Encephalitis Virus is Immunogenic in HLA Transgenic Mice

    Science.gov (United States)

    2017-04-07

    1 An immunoinformatics-derived DNA vaccine encoding human Class II T cell epitopes of 1 Ebola virus, Sudan virus, and Venezuelan equine...connie.s.schmaljohn.civ@mail.mil 13 14 Keywords: genome-derived vaccine, epitope-based vaccine, DNA vaccine, peptide vaccine, T 15 cell epitope, Ebola virus, EBOV...for biodefense. We previously developed and 53 tested DNA vaccines expressing the envelope glycoproteins of these viruses in mice and 54 nonhuman

  20. Glutamic acid at residue 125 of the prM helix domain interacts with positively charged amino acids in E protein domain II for Japanese encephalitis virus-like-particle production.

    Science.gov (United States)

    Peng, Jia-Guan; Wu, Suh-Chin

    2014-08-01

    Interaction between E and prM proteins in flavivirus-infected cells is a major factor for virus-like particle (VLP) production. The prM helical (prM-H) domain is topologically close to and may interact with domain II of the E protein (EDII). In this study, we investigated prM-H domain amino acid residues facing Japanese encephalitis virus EDII using site-directed mutagenesis to determine their roles in prM-E interaction and VLP production. Our results indicate that negatively charged prM-E125 residue at the prM-H domain affected VLP production via one or more interactions with positively charged E-K93 and E-H246 residues at EDII. Exchanges of oppositely charged residue side chains at prM-E125/E-K93 and prM-E125/E-H246 are recoverable for VLP production. The prM-E125 and E-H246 residues are conserved and that the positive charge of the E-K93 residue is preserved in different flavivirus groups. These findings suggest that the electrostatic attractions of prM-E125, E-K93, and E-H246 residues are important to flavivirus VLP production and that inhibiting these interactions is a potential strategy for blocking flavivirus infections. Molecular interaction between E and prM proteins of Japanese encephalitis virus is a major driving force for virus-like particle (VLP) production. The current high-resolution structures available for prM-E complexes do not include the membrane proximal stem region of prM. The prM stem region contains an N-terminal loop and a helix domain (prM-H). Since the prM-H domain is topologically close to domain II of the E protein (EDII), this study was to determine molecular interactions between the prM-H domain and EDII. We found that the molecular interactions between prM-E125 residue and positively charged E-K93 and E-H246 residues at EDII are critical for VLP production. More importantly, the prM-E125 and E-H246 residues are conserved and the positive charge of the E-K93 residue is preserved in different flavivirus groups. Our findings help

  1. Tick-Borne Langat/Mosquito-Borne Dengue Flavivirus Chimera, a Candidate Live Attenuated Vaccine for Protection against Disease Caused by Members of the Tick-Borne Encephalitis Virus Complex: Evaluation in Rhesus Monkeys and in Mosquitoes

    Science.gov (United States)

    Pletnev, Alexander G.; Bray, Michael; Hanley, Kathryn A.; Speicher, Jim; Elkins, Randy

    2001-01-01

    Langat virus (LGT), strain TP21, a naturally avirulent tick-borne flavivirus, was used to construct a chimeric candidate virus vaccine which contained LGT genes for premembrane (preM) and envelope (E) glycoprotein and all other sequences derived from dengue type 4 virus (DEN4). The live virus vaccine was developed to provide resistance to the highly virulent, closely related tick-borne flaviviruses that share protective E epitopes among themselves and with LGT. Toward that end the chimera, initially recovered in mosquito cells, was adapted to grow to high titer in qualified simian Vero cells. When inoculated intraperitoneally (i.p.), the Vero cell-adapted LGT TP21/DEN4 chimera remained completely attenuated for SCID mice. Significantly, the chimera protected immunocompetent mice against the most virulent tick-borne encephalitis virus (TBEV). Subsequently, rhesus monkeys were immunized in groups of 4 with 105 or 107 PFU of LGT strain TP21, with 105 PFU of DEN4, or with 103, 105, or 107 PFU of the chimera. Each of the monkeys inoculated with DEN4 or LGT TP21 became viremic, and the duration of viremia ranged from 1 to 5 days. In contrast, viremia was detected in only 1 of 12 monkeys inoculated with the LGT TP21/DEN4 chimera; in this instance the level of viremia was at the limit of detection. All monkeys immunized with the chimera or LGT TP21 virus developed a moderate to high level of neutralizing antibodies against LGT TP21 as well as TBEV and were completely protected against subsequent LGT TP21 challenge, whereas monkeys previously immunized with DEN4 virus became viremic when challenged with LGT TP21. These observations suggest that the chimera is attenuated, immunogenic, and able to induce a protective immune response. Furthermore, passive transfer of serum from monkeys immunized with chimera conferred significant protection to mice subsequently challenged with 100 i.p. 50% lethal doses of the highly virulent TBEV. The issue of transmissibility of the chimera

  2. A Novel, Rapid Assay for Detection and Differentiation of Serotype-Specific Antibodies to Venezuelan Equine Encephalitis Complex Alphaviruses

    National Research Council Canada - National Science Library

    Wang, Eryu; Paessler, Slobodan; Smith, Darci R; Coffey, Lark L; Kang, Wenli; Estrada-Franco, Jose; Weaver, Scott C; Aguilar, Patricia V; Pfeffer, Martin; Olson, James

    2005-01-01

    ... of Venezuelan equine encephalitis (VEE) virus. Two monoclonal antibodies that differentially recognize epizootic versus enzootic VEE virus epitopes were used to measure the serotype-specific blocking abilities of antibodies in sera of naturally...

  3. Tick-borne encephalitis in children: an update on epidemiology and diagnosis.

    Science.gov (United States)

    Arnez, Maja; Avsic-Zupanc, Tatjana

    2009-12-01

    Tick-borne encephalitis is an infection of the CNS caused by a tick-borne encephalitis virus transmitted by ticks. It is more common in adults than in children. During the last 30 years, the incidence of the disease increased continuously in almost all endemic European countries except Austria. Many factors are responsible for the increased incidence. However, in Austria, the incidence of tick-borne encephalitis decreased dramatically since the introduction of a well-organized vaccination campaign against tick-borne encephalitis. The diagnosis of tick-borne encephalitis is based on clinical criteria and laboratory confirmation of infection. Other tick-borne diseases, such as Lyme borreliosis and human granulocytic anaplasmosis, should be considered in children with tick-borne encephalitis since endemic areas for all three diseases overlap.

  4. Eastern equine encephalitis.

    Science.gov (United States)

    Berlin, Daniel; Gilani, Ahmed I; Grewal, Amrit K; Fowkes, Mary

    2017-10-01

    We describe a patient who died from a fulminant presentation of encephalitis. After an exhaustive search, we found no treatable cause. Postmortem PCR analysis of brain tissue led to a diagnosis of eastern equine encephalitis. We have identified several clinical pearls that may assist others in making the diagnosis earlier in the disease course. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Proceedings of the Department of Defense (DoD) Symposium. DoD Entomology: Global, Diverse, and Improving Public Health

    Science.gov (United States)

    2010-12-14

    physiological responses of house flies shows a direct correlation of attractiveness to visual targets and the intensity of neurological response...Yellow, however, was the exception. Yellow was repellent to house flies, but it triggered a relatively high neurological response. Filth fly...arboviruses, including dengue virus, yellow fever virus, Venezuelan equine encephalitis virus (VEEV), Oropouche virus, Mayaro virus, and two

  6. Public Health Laboratory Surveillance and Diagnosis of Japanese Encephalitis: Time to Revisit.

    Science.gov (United States)

    Kakkar, Manish; Dhole, Tapan N; Rogawski, Elizabeth T; Chaturvedi, Sanjay

    2016-01-01

    We assessed detection of recent Japanese encephalitis virus infection using recommended strategy. Cross-sectional community-based study conducted in 12 villages in Kushinagar, Uttar-Pradesh, India in 2012-13. Recent infection with Japanese encephalitis virus in 239 healthy children aged 1-15 year was detected using a combination of serology and molecular methods. 24 (10%) children showed recent infection; 2 by serology and 22 by molecular method. Symptomatic cases were estimated as 626 in Kushinagar against reported 139 in all age groups across the state. Lower positivity using recommended serology suggests major gap in existing surveillance and diagnostic protocols and estimation of burden of Japanese encephalitis.

  7. An enzyme immunoassay for detection of Japanese encephalitis ...

    Indian Academy of Sciences (India)

    Japanese encephalitis virus (JEV) induces human peripheral blood monocytes to secrete a chemotactic cytokine [human macrophage-derived factor (hMDF)] which causes chemotaxis of neutrophils. The only known assay for hMDF cannot quantify its level in samples, so an enzyme immunoassay has been standardized for ...

  8. Noncoding subgenomic flavivirus RNA: multiple functions in West Nile virus pathogenesis and modulation of host responses

    NARCIS (Netherlands)

    Roby, J.A.; Pijlman, G.P.; Wilusz, J.; Khromykh, A.A.

    2014-01-01

    Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested so far are

  9. Reactivation of herpes simplex virus-1 following epilepsy surgery

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2015-01-01

    Conclusion: The authors stress the potential risk of reactivation of HSV encephalitis after intracranial surgery. Herpes simplex virus encephalitis must be considered in neurosurgical patients who develop postoperative seizures and fever.

  10. Current recommendations for the Japanese encephalitis vaccine.

    Science.gov (United States)

    Chen, Hui-Lan; Chang, Jia-Kan; Tang, Ren-Bin

    2015-05-01

    Japanese encephalitis (JE) is a mosquito-borne flavivirus infection and an important cause of encephalitis in most of Asia and parts of the western Pacific. Most people infected with the JE virus (JEV) are asymptomatic or seemingly suffer from a nonspecific, flu-like illness; in others, JE can cause illness ranging from fever and headache to severe encephalitis. Although it can cause significant morbidity and mortality, JE is a vaccine-preventable disease, and vaccination programs have proven most effective in preventing and diminishing the burden of disease. Such JE vaccines have been available for decades with four types of JE vaccines-live attenuated SA14-14-2 vaccine, inactivated mouse brain-derived vaccine (JE-MB), inactivated Vero cell culture vaccine (JE-VC), and live attenuated chimeric vaccine (IMOJEV)-and are currently used in most countries. In some Asian countries such as Japan, China, Taiwan, Korea, and Thailand, immunization programs have been conducted for children and so the ongoing incidence of JE has declined considerably in recent decades. Until quite recently, the primary JE vaccine in use internationally has been the JE-MB, which is now commonly replaced by cell culture-based vaccines. Copyright © 2015. Published by Elsevier Taiwan.

  11. Management of adult infectious encephalitis in metropolitan France.

    Science.gov (United States)

    Goulenok, T; Buzelé, R; Duval, X; Bruneel, F; Stahl, J P; Fantin, B

    2017-05-01

    Infectious encephalitis is a severe disease leading to a high mortality and morbidity. The most frequent causes include Herpes simplex virus, Varicella Zoster virus, Listeria monocytogenes, and Mycobacterium tuberculosis. Urgent treatment is required (anti-infective therapy and nonspecific supportive care). The aim of this study was to define treatment strategy, empirical and after microbiological documentation at 48hours, through a systematic literature review. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Immune-enhancing effect of nano-DNA vaccine encoding a gene of the prME protein of Japanese encephalitis virus and BALB/c mouse granulocyte-macrophage colony-stimulating factor.

    Science.gov (United States)

    Zhai, Yongzhen; Zhou, Yan; Li, Ximei; Feng, Guohe

    2015-07-01

    Plasmid-encoded granulocyte-macrophage colony-stimulating factor (GM‑CSF) is an adjuvant for genetic vaccines; however, how GM-CSF enhances immunogenicity remains to be elucidated. In the present study, it was demonstrated that injection of a plasmid encoding the premembrane (prM) and envelope (E) protein of Japanese encephalitis virus and mouse GM-CSF (pJME/GM-CSF) into mouse muscle recruited large and multifocal conglomerates of macrophages and granulocytes, predominantly neutrophils. During the peak of the infiltration, an appreciable number of immature dendritic cells (DCs) appeared, although no T and B-cells was detected. pJME/GM-CSF increased the number of splenic DCs and the expression of major histocompatibility complex class II (MHCII) on splenic DC, and enhanced the antigenic capture, processing and presentation functions of splenic DCs, and the cell-mediated immunity induced by the vaccine. These findings suggested that the immune-enhancing effect by pJME/GM-CSF was associated with infiltrate size and the appearance of integrin αx (CD11c)+cells. Chitosan-pJME/GM-CSF nanoparticles, prepared by coacervation via intramuscular injection, outperformed standard pJME/GM-CSF administrations in DC recruitment, antigen processing and presentation, and vaccine enhancement. This revealed that muscular injection of chitosan‑pJME/GM-CSF nanoparticles may enhance the immunoadjuvant properties of GM-CSF.

  13. Encephalitis in primary HIV infection

    DEFF Research Database (Denmark)

    Helleberg, M; Kirk, O

    2013-01-01

    We report a case of primary HIV encephalitis, which initially presented as acute psychosis. Magnetic resonance imaging of the brain was suggestive of vasculitis and multiple infarctions, whereas a brain biopsy after six weeks of symptoms showed HIV encephalitis with microglial nodules, but no signs...... of vasculitis. We review previous reported cases and radiological findings in HIV encephalitis and discuss the role of antiretroviral therapy and steroids in its management....

  14. Replicon-Helper Systems from Attenuated Venezuelan Equine Encephalitis Virus: Expression of Heterologous Genes in Vitro and Immunization Against Heterologous Pathogens in Vivo

    National Research Council Canada - National Science Library

    Pushko, Peter

    1997-01-01

    ...) or the Lassa virus nucleocapsid (N) gene, and upon transfection into eukaryotic cells by electroportation, these replicon RNAs directed the efficient, high-level synthesis of the HA or N proteins...

  15. Epidemiology of Japanese encephalitis: past, present, and future prospects

    Science.gov (United States)

    Wang, Huanyu; Liang, Guodong

    2015-01-01

    Japanese encephalitis (JE) is one of severe viral encephalitis that affects individuals in Asia, western Pacific countries, and northern Australia. Although 67,900 JE cases have been estimated among 24 JE epidemic countries annually, only 10,426 have been reported in 2011. With the establishment of JE surveillance and vaccine use in some countries, the JE incidence rate has decreased; however, serious outbreaks still occur. Understanding JE epidemics and identifying the circulating JE virus genotypes will improve JE prevention and control. This review summarizes the current epidemiology data in these countries. PMID:25848290

  16. Multicystic encephalomalacia due to fetal viral encephalitis.

    Science.gov (United States)

    Lyen, K R; Lingam, S; Butterfill, A M; Marshall, W C; Dobbing, C J; Lee, D S

    1981-09-01

    Two children, aged 2 weeks and 2 months, with multicystic encephalomalacia aer described. Although computerized tomography (CT) scan was used for the diagnosis, the value of the simple method of transillumination is stressed. The mother of one child had mumps with meningitis at 26 weeks' gestation. The other child had an echovirus 11 isolated from the cerebrospinal fluid and herpesvirus hominis (HVH) from the skin at 8 weeks. We speculate that the changes in the brains of these babies may be due to the respective viruses causing a fetal encephalitis.

  17. Mechanism of Innate Resistance to Viral Encephalitis.

    Science.gov (United States)

    1976-12-01

    SECURITY CLASIFICATION OF THIS PA5(Wh Data atm4) -J strains after IP inoculation and mortality was high in C3H/He mice whereas mortality was low in...early studies, indicated that Banzi virus was about 100,000 times more lethal for adult He mice than for adult RV mice follow- ing intraperitoneal (IP...high as the LD50 decreased. He mice were highly susceptible to lethal encephalitis as weanlings and as adults (Table 3). Mortality among RV and He mice

  18. Moyamoya Disease Mimicking Encephalitis

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    Maryam Khalesi

    2014-09-01

    Full Text Available Moyamoya disease is a rare vaso-occlusive illness with an unknown etiology characterized by stenosis of the internal carotid arteries with spontaneous development of a collateral vascular network. A 15-month-old girl was referred to the emergency ward of Imam Reza Hospital due to decreased level of consciousness, focal seizures and fever during the previous 24 hours with an impression of encephalitis. Physical examination revealed left side hemiparesis; however brain CT-Scan did not show any significant lesions. Initial therapy with vancomycin, ceftriaxone and acyclovir was administered. CSF analysis did not show any abnormality and the blood as well as CSF cultures results were negative. Brain MRI showed hyperintensity at right frontal and parietal regions, suggesting vascular lesion. Magnetic resonance angiography (MRA showed bilaterally multiple torsions in vessels at the basal ganglia consistent with moyamoya vessels. In all children exhibiting encephalitis, vascular events such as moyamoya disease should be considered. Brain MRI is a critical tool for this purpose. Common causes of encephalitis such as herpes simplex should also be ruled out.

  19. Epilepsy surgery for epileptic encephalopathy as a sequela of herpes simplex encephalitis: case report.

    Science.gov (United States)

    Taskin, Birce Dilge; Tanji, Kurenai; Feldstein, Neil A; McSwiggan-Hardin, Maureen; Akman, Cigdem I

    2017-07-01

    Herpes simplex virus (HSV) encephalitis can manifest with different clinical presentations, including acute monophasic illness and biphasic chronic granulomatous HSV encephalitis. Chronic encephalitis is much less common, and very rare late relapses are associated with intractable epilepsy and progressive neurological deficits with or without evidence of HSV in the cerebrospinal fluid. The authors report on an 8-year-old girl with a history of treated HSV-1 encephalitis when she was 13 months of age and focal epilepsy when she was 2 years old. Although free of clinical seizures, when she was 5, she experienced behavioral and academic dysfunction, which was later attributed to electrographic focal seizures and worsening electroencephalography (EEG) findings with electrical status epilepticus during slow-wave sleep (ESES). Following a right temporal lobectomy, chronic granulomatous encephalitis was diagnosed. The patient's clinical course improved with the resolution of seizures and EEG abnormalities.

  20. Japanese encephalitis: a review of the Indian perspective

    Directory of Open Access Journals (Sweden)

    Sarika Tiwari

    2012-12-01

    Full Text Available Japanese encephalitis virus (JEV causes Japanese encephalitis, which is a leading form of viral encephalitis in Asia, with around 50,000 cases and 10,000 deaths per year in children below 15 years of age. The JEV has shown a tendency to extend to other geographic regions. Case fatality averages 30% and a high percentage of the survivors are left with permanent neuropsychiatric sequelae. Currently, there is no cure for JEV, and treatment is mainly supportive. Patients are not infectious, but should avoid further mosquito bites. A number of antiviral agents have been investigated; however, none of these have convincingly been shown to improve the outcome of JEV. In this review, the current knowledge of the epidemiology and the pathogenesis of this deadly disease have been summarized.

  1. Japanese encephalitis: a review of the Indian perspective.

    Science.gov (United States)

    Tiwari, Sarika; Singh, Rishi Kumar; Tiwari, Ruchi; Dhole, Tapan N

    2012-01-01

    Japanese encephalitis virus (JEV) causes Japanese encephalitis, which is a leading form of viral encephalitis in Asia, with around 50,000 cases and 10,000 deaths per year in children below 15 years of age. The JEV has shown a tendency to extend to other geographic regions. Case fatality averages 30% and a high percentage of the survivors are left with permanent neuropsychiatric sequelae. Currently, there is no cure for JEV, and treatment is mainly supportive. Patients are not infectious, but should avoid further mosquito bites. A number of antiviral agents have been investigated; however, none of these have convincingly been shown to improve the outcome of JEV. In this review, the current knowledge of the epidemiology and the pathogenesis of this deadly disease have been summarized. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

  2. Japanese encephalitis: a review of the Indian perspective

    Directory of Open Access Journals (Sweden)

    Sarika Tiwari

    Full Text Available Japanese encephalitis virus (JEV causes Japanese encephalitis, which is a leading form of viral encephalitis in Asia, with around 50,000 cases and 10,000 deaths per year in children below 15 years of age. The JEV has shown a tendency to extend to other geographic regions. Case fatality averages 30% and a high percentage of the survivors are left with permanent neuropsychiatric sequelae. Currently, there is no cure for JEV, and treatment is mainly supportive. Patients are not infectious, but should avoid further mosquito bites. A number of antiviral agents have been investigated; however, none of these have convincingly been shown to improve the outcome of JEV. In this review, the current knowledge of the epidemiology and the pathogenesis of this deadly disease have been summarized.

  3. Multiphasic presentation of Rasmussen's encephalitis

    NARCIS (Netherlands)

    Avbersek, A.; Miserocchi, A.; McEvoy, A.W.; Patel, A.V.; Aronica, E.; Blumcke, I.; Jacques, T.S.; Acheson, J.; Thom, M.; Sisodiya, S.M.

    2015-01-01

    Rasmussen's encephalitis is a rare, chronic inflammatory disorder of unknown cause, characterised by drug-resistant focal epilepsy that may rarely present in adolescence or adulthood. We present a case of Rasmussen's encephalitis with prominent recurrent fluctuation in symptoms and well-documented

  4. MRI Findings In Dengue Encephalitis

    Directory of Open Access Journals (Sweden)

    Ashraf V.V

    2004-01-01

    Full Text Available Neurological manifestations are rare in dengue fever. Two cases with encephalopathy and systemic features of dengue fever with abnormal CSF and MR imaging are reported. Striking MRI finding was bilateral symmetrical thalamic lesions similar to those reported in Japanese encephalitis. This report highlights that MRI findings can be similar in dengue and Japanese encephalitis.

  5. Eastern equine encephalitis: an emerging arboviral disease threat, Maine, 2009.

    Science.gov (United States)

    Gibney, Katherine B; Robinson, Sara; Mutebi, John-Paul; Hoenig, Donald E; Bernier, Brian J; Webber, Lori; Lubelczyk, Charles; Nett, Randall J; Fischer, Marc

    2011-06-01

    Eastern equine encephalitis (EEE) is one of the most severe arboviral encephalitides in North America. Before 2009, limited nonhuman EEE virus activity had been reported in Maine, all from the southernmost area of the state. No human case has been reported in a Maine resident. We review all EEE virus activity reported to Maine Centers for Disease Control in 2009 and describe current testing practices for possible human EEE cases. In 2009, fatal cases of EEE were identified in 15 horses, 1 llama, and 3 flocks of pheasants in Maine, with activity extending into the central part of the state. Although no human EEE cases were identified, diagnostic testing practices of most meningitis and encephalitis cases were inadequate to exclude EEE. Work to better define the expanding range of EEE virus in Maine is warranted, along with education of healthcare providers regarding appropriate testing for this serious disease.

  6. Epidemiology of Japanese encephalitis in the Philippines: a systematic review.

    Science.gov (United States)

    Lopez, Anna Lena; Aldaba, Josephine G; Roque, Vito G; Tandoc, Amado O; Sy, Ava Kristy; Espino, Fe Esperanza; DeQuiroz-Castro, Maricel; Jee, Youngmee; Ducusin, Maria Joyce; Fox, Kimberley K

    2015-03-01

    Japanese encephalitis virus (JEV) is an important cause of encephalitis in most of Asia, with high case fatality rates and often significant neurologic sequelae among survivors. The epidemiology of JE in the Philippines is not well defined. To support consideration of JE vaccine for introduction into the national schedule in the Philippines, we conducted a systematic literature review and summarized JE surveillance data from 2011 to 2014. We conducted searches on Japanese encephalitis and the Philippines in four databases and one library. Data from acute encephalitis syndrome (AES) and JE surveillance and from the national reference laboratory from January 2011 to March 2014 were tabulated and mapped. We identified 29 published reports and presentations on JE in the Philippines, including 5 serologic surveys, 18 reports of clinical cases, and 8 animal studies (including two with both clinical cases and animal data). The 18 clinical studies reported 257 cases of laboratory-confirmed JE from 1972 to 2013. JE virus (JEV) was the causative agent in 7% to 18% of cases of clinical meningitis and encephalitis combined, and 16% to 40% of clinical encephalitis cases. JE predominantly affected children under 15 years of age and 6% to 7% of cases resulted in death. Surveillance data from January 2011 to March 2014 identified 73 (15%) laboratory-confirmed JE cases out of 497 cases tested. This comprehensive review demonstrates the endemicity and extensive geographic range of JE in the Philippines, and supports the use of JE vaccine in the country. Continued and improved surveillance with laboratory confirmation is needed to systematically quantify the burden of JE, to provide information that can guide prioritization of high risk areas in the country and determination of appropriate age and schedule of vaccine introduction, and to measure the impact of preventive measures including immunization against this important public health threat.

  7. Japanese encephalitis virus induces matrix metalloproteinase-9 expression via a ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent AP-1 pathway in rat brain astrocytes

    Directory of Open Access Journals (Sweden)

    Yang Chuen-Mao

    2012-01-01

    Full Text Available Abstract Background Japanese encephalitis virus (JEV infection is a major cause of acute encephalopathy in children, which destroys central nervous system (CNS cells, including astrocytes and neurons. Matrix metalloproteinase (MMP-9 has been shown to degrade components of the basal lamina, leading to disruption of the blood-brain barrier (BBB and to contribute to neuroinflammatory responses in many neurological diseases. However, the detailed mechanisms of JEV-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells are largely unclear. Methods In this study, the effect of JEV on expression of MMP-9 was determined by gelatin zymography, western blot analysis, RT-PCR, and promoter assay. The involvement of AP-1 (c-Jun and c-Fos, c-Src, PDGFR, PI3K/Akt, and MAPKs in these responses were investigated by using the selective pharmacological inhibitors and transfection with siRNAs. Results Here, we demonstrate that JEV induces expression of pro-form MMP-9 via ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent, AP-1 activation in RBA-1 cells. JEV-induced MMP-9 expression and promoter activity were inhibited by pretreatment with inhibitors of AP-1 (tanshinone, c-Src (PP1, PDGFR (AG1296, and PI3K (LY294002, and by transfection with siRNAs of c-Jun, c-Fos, PDGFR, and Akt. Moreover, JEV-stimulated AP-1 activation was inhibited by pretreatment with the inhibitors of c-Src, PDGFR, PI3K, and MAPKs. Conclusion From these results, we conclude that JEV activates the ROS/c-Src/PDGFR/PI3K/Akt/MAPKs pathway, which in turn triggers AP-1 activation and ultimately induces MMP-9 expression in RBA-1 cells. These findings concerning JEV-induced MMP-9 expression in RBA-1 cells imply that JEV might play an important role in CNS inflammation and diseases.

  8. Japanese encephalitis virus induces matrix metalloproteinase-9 expression via a ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent AP-1 pathway in rat brain astrocytes.

    Science.gov (United States)

    Yang, Chuen-Mao; Lin, Chih-Chung; Lee, I-Ta; Lin, Yi-Hsin; Yang, Caleb M; Chen, Wei-June; Jou, Mei-Jie; Hsiao, Li-Der

    2012-01-18

    Japanese encephalitis virus (JEV) infection is a major cause of acute encephalopathy in children, which destroys central nervous system (CNS) cells, including astrocytes and neurons. Matrix metalloproteinase (MMP)-9 has been shown to degrade components of the basal lamina, leading to disruption of the blood-brain barrier (BBB) and to contribute to neuroinflammatory responses in many neurological diseases. However, the detailed mechanisms of JEV-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells) are largely unclear. In this study, the effect of JEV on expression of MMP-9 was determined by gelatin zymography, western blot analysis, RT-PCR, and promoter assay. The involvement of AP-1 (c-Jun and c-Fos), c-Src, PDGFR, PI3K/Akt, and MAPKs in these responses were investigated by using the selective pharmacological inhibitors and transfection with siRNAs. Here, we demonstrate that JEV induces expression of pro-form MMP-9 via ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent, AP-1 activation in RBA-1 cells. JEV-induced MMP-9 expression and promoter activity were inhibited by pretreatment with inhibitors of AP-1 (tanshinone), c-Src (PP1), PDGFR (AG1296), and PI3K (LY294002), and by transfection with siRNAs of c-Jun, c-Fos, PDGFR, and Akt. Moreover, JEV-stimulated AP-1 activation was inhibited by pretreatment with the inhibitors of c-Src, PDGFR, PI3K, and MAPKs. From these results, we conclude that JEV activates the ROS/c-Src/PDGFR/PI3K/Akt/MAPKs pathway, which in turn triggers AP-1 activation and ultimately induces MMP-9 expression in RBA-1 cells. These findings concerning JEV-induced MMP-9 expression in RBA-1 cells imply that JEV might play an important role in CNS inflammation and diseases.

  9. Assessing the abundance, seasonal questing activity, and Borrelia and tick-borne encephalitis virus (TBEV) prevalence of Ixodes ricinus ticks in a Lyme borreliosis endemic area in Southwest Finland.

    Science.gov (United States)

    Sormunen, Jani J; Klemola, Tero; Vesterinen, Eero J; Vuorinen, Ilppo; Hytönen, Jukka; Hänninen, Jari; Ruohomäki, Kai; Sääksjärvi, Ilari E; Tonteri, Elina; Penttinen, Ritva

    2016-02-01

    Studies have revealed that Ixodes ricinus (Acari: Ixodidae) have become more abundant and their geographical distribution extended northwards in some Nordic countries during the past few decades. However, ecological data of tick populations in Finland are sparse. In the current study, I. ricinus abundance, seasonal questing activity, and their Borrelia spp. and tick-borne encephalitis virus (TBEV) prevalence were evaluated in a Lyme borreliosis endemic area in Southwest Finland, Seili Island, where a previous study mapping tick densities was conducted 12 years earlier. A total of 1940 ticks were collected from five different biotopes by cloth dragging during May-September 2012. The overall tick density observed was 5.2 ticks/100m(2) for nymphs and adults. Seasonal questing activity of ticks differed between biotopes and life stages: bimodal occurrences were observed especially for nymphal and adult ticks in forested biotopes, while larvae in pastures exhibited mostly unimodal occurrence. Prevalence of Borrelia and TBEV in ticks was evaluated using conventional and real-time PCR. All samples were negative for TBEV. Borrelia prevalence was 25.0% for adults (n=44) and the minimum infection rate (MIR) 5.6% for pooled nymph samples (191 samples, 1-14 individuals per sample; 30/191 positive). No Borrelia were detected in pooled larval samples (63 samples, 1-139 individuals per sample). Five species of Borrelia were identified from the samples: B. afzelii, B. burgdorferi s.s., B. garinii, B. valaisiana and B. miyamotoi. In Finland, B. valaisiana and B. miyamotoi have previously been reported from the Åland Islands but not from the mainland or inner archipelago. The results of the present study suggest an increase in I. ricinus abundance on the island. Copyright © 2015 Elsevier GmbH. All rights reserved.

  10. A randomized study of the immunogenicity and safety of Japanese encephalitis chimeric virus vaccine (JE-CV) in comparison with SA14-14-2 vaccine in children in the Republic of Korea.

    Science.gov (United States)

    Kim, Dong Soo; Houillon, Guy; Jang, Gwang Cheon; Cha, Sung-Ho; Choi, Soo-Han; Lee, Jin; Kim, Hwang Min; Kim, Ji Hong; Kang, Jin Han; Kim, Jong-Hyun; Kim, Ki Hwan; Kim, Hee Soo; Bang, Joon; Naimi, Zulaikha; Bosch-Castells, Valérie; Boaz, Mark; Bouckenooghe, Alain

    2014-01-01

    A new live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) has been developed based on innovative technology to give protection against JE with an improved immunogenicity and safety profile. In this phase 3, observer-blind study, 274 children aged 12-24 months were randomized 1:1 to receive one dose of JE-CV (Group JE-CV) or the SA14-14-2 vaccine currently used to vaccinate against JE in the Republic of Korea (Group SA14-14-2). JE neutralizing antibody titers were assessed using PRNT50 before and 28 days after vaccination. The primary endpoint of non-inferiority of seroconversion rates on D28 was demonstrated in the Per Protocol analysis set as the difference between Group JE-CV and Group SA14-14-2 was 0.9 percentage points (95% confidence interval [CI]: -2.35; 4.68), which was above the required -10%. Seroconversion and seroprotection rates 28 days after administration of a single vaccine dose were 100% in Group JE-CV and 99.1% in Group SA14-14-2; all children except one (Group SA14-14-2) were seroprotected. Geometric mean titers (GMTs) increased in both groups from D0 to D28; GM of titer ratios were slightly higher in Group JE-CV (182 [95% CI: 131; 251]) than Group SA14-14-2 (116 [95% CI: 85.5, 157]). A single dose of JE-CV was well tolerated and no safety concerns were identified. In conclusion, a single dose of JE-CV or SA14-14-2 vaccine elicited a comparable immune response with a good safety profile. Results obtained in healthy Korean children aged 12-24 months vaccinated with JE-CV are consistent with those obtained in previous studies conducted with JE-CV in toddlers.

  11. MRI in Japanese encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, S. [Sanjay Gandhi Post Graduate Inst. of Medical Sciences, Lucknow (India). Dept. of Radiology; Misra, U.K. [Sanjay Gandhi Post Graduate Inst. of Medical Sciences, Lucknow (India). Dept. of Neurology; Kalita, J. [Sanjay Gandhi Post Graduate Inst. of Medical Sciences, Lucknow (India). Dept. of Neurology; Salwani, V. [Sanjay Gandhi Post Graduate Inst. of Medical Sciences, Lucknow (India). Dept. of Radiology; Gupta, R.K. [Sanjay Gandhi Post Graduate Inst. of Medical Sciences, Lucknow (India). Dept. of Radiology; Gujral, R. [Sanjay Gandhi Post Graduate Inst. of Medical Sciences, Lucknow (India). Dept. of Radiology

    1997-03-01

    We document the MRI features in seven patients with Japanese encephalitis. MRI was carried out on a 1.5 T system within 10-60 days of onset. In all the patients MRI revealed bilateral thalamic lesions, haemorrhagic in five. Signal changes were present in the cerebrum in four patients, the midbrain and cerebellum in three each, the pons in two and the basal ganglia in one. The lesions were haemorrhagic in three of the four patients with lesions in the cortex, two of the three with lesions in the midbrain and cerebellum, but the pontine lesions were haemorrhagic in both patients. Spinal cord involvement was seen in one of the three patients who underwent MRI. In two patients MRI was repeated 3 years after the onset, showing marked reduction in abnormal signal; and all the lesions gave low signal on both T1- and T2-weighted images. Bilateral thalamic involvement, especially haemorrhagic, may be considered characteristic of Japanese encephalitis, especially in endemic areas. (orig.)

  12. Incidence of Japanese Encephalitis among Acute Encephalitis Syndrome Cases in West Bengal, India

    Directory of Open Access Journals (Sweden)

    Bhaswati Bandyopadhyay

    2013-01-01

    Full Text Available Background and Objectives. Japanese encephalitis (JE is the most important cause of acute and epidemic viral encephalitis. Every year sporadic JE cases are reported from the various districts of West Bengal, indicating its endemicity in this state. JE vaccination programme has been undertaken by the State Health Department of West Bengal. This study was aimed at seeing the present scenario of JE among acute encephalitis syndrome (AES cases in West Bengal. Materials and Methods. Blood and/or CSF samples were referred from suspected AES cases to the referral virology laboratory of the Calcutta School of Tropical Medicine from different hospitals of Kolkata. IgM antibody capture ELISA was performed on the CSF and serum samples by JE virus MAC ELISA kit supplied by the National Institute of Virology, Pune. Results. The present study reveals that 22.76% and 5% of the AES cases were positive for JE IgM in 2011 and 2012, respectively. JE is mainly prevalent in children and adolescents below 20 years of age with no gender predilection. Although the percentages of JE positive cases were high in 2011, it sharply decreased thereafter possibly due to better awareness programs, due to mass vaccination, or simply due to natural epidemiological niche periodicity due to herd immunity.

  13. Focal encephalitis with enterovirus infections.

    Science.gov (United States)

    Modlin, J F; Dagan, R; Berlin, L E; Virshup, D M; Yolken, R H; Menegus, M

    1991-10-01

    We report on four pediatric patients with Enterovirus infections who were admitted to the hospital with signs or symptoms of acute, focal encephalitis. All four experienced focal seizures. Each had a cerebrospinal fluid pleocytosis at the initial lumbar puncture. In all four patients the diagnosis of herpes simplex encephalitis was entertained. Each child improved spontaneously within a few days of admission to the hospital, and only one had residual neurologic abnormalities at the time of discharge. A brief review of these cases, and three additional cases from the literature, indicate that the enteroviruses, particularly the group A Coxsackieviruses, are rare causes of acute focal encephalitis in children and adolescents.

  14. Oropuche virus: A virus present but ignored

    Directory of Open Access Journals (Sweden)

    Salim Mattar V.

    2015-09-01

    Full Text Available Bunyaviruses are RNA viruses that affect animals and plants; they have five genera and four of them affect humans: Orthobunyavirus, Nairovirus, Phlebovirus and Hantavirus. All of them are Arbovirus, except Hantavirus. The Orthobunyaviruses comprise Oropouche, Tahyna, La Crosse virus, California encephalitis virus and Heartland virus recently discovered (1. Except for Heartland virus which is transmitted by ticks of the genus Amblyoma, these Phleboviruses have as vectors mosquitoes, which bite small mammals which are able to be as reservoirs amplifiers.

  15. Granulomatous herpes simplex encephalitis in an infant with multicystic encephalopathy: a distinct clinicopathologic entity?

    Science.gov (United States)

    Schutz, Peter W; Fauth, Clarissa T; Al-Rawahi, Ghada N; Pugash, Denise; White, Valerie A; Stockler, Sylvia; Dunham, Christopher P

    2014-04-01

    Herpes simplex virus encephalitis can manifest as a range of clinical presentations including classic adult, neonatal, and biphasic chronic-granulomatous herpes encephalitis. We report an infant with granulomatous herpes simplex virus type 2 encephalitis with a subacute course and multicystic encephalopathy. A 2-month-old girl presented with lethargy and hypothermia. Computed tomography scan of the head showed multicystic encephalopathy and calcifications. Cerebrospinal fluid analysis by polymerase chain reaction testing for herpes simplex virus 1 and 2, enterovirus, and cytomegalovirus was negative. Normal cerebrospinal fluid interferon-α levels argued against Aicardi-Goutières syndrome. The patient died 2 weeks after presentation. At autopsy, multicystic encephalopathy was confirmed with bilateral gliosis, granulomatous inflammation with multinucleated giant cells, and calcifications. Bilateral healing necrotizing retinitis suggested a viral etiology, but retina and brain were free of viral inclusions and immunohistochemically negative for herpes simplex virus-2 and cytomegalovirus. However, polymerase chain reaction analysis showed herpes simplex virus-2 DNA in four cerebral paraffin blocks. Subsequent repeat testing of the initial cerebrospinal fluid sample using a different polymerase chain reaction assay was weakly positive for herpes simplex virus-2 DNA. Granulomatous herpes simplex virus encephalitis in infants can present with subacute course and result in multicystic encephalopathy with mineralization and minimal cerebrospinal fluid herpes simplex virus DNA load. Infectious etiologies should be carefully investigated in the differential diagnosis of multicystic encephalopathy with mineralization, in particular if multinucleated giant cells are present. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Autoimmune encephalitis and sleep disorders

    Directory of Open Access Journals (Sweden)

    Yan HUANG

    2017-10-01

    Full Text Available Research shows that autoimmune encephalitis is associated with sleep disorders. Paraneoplastic neurological syndrome (PNS with Ma2 antibodies can cause sleep disorders, particularly narcolepsy and rapid eye movement sleep behavior disorder (RBD. Limbic encephalitis (LE and Morvan syndrome, associated with voltage - gated potassium channel (VGKC-complex antibodies, which include leucine-rich glioma-inactivated 1 (LGI1 antibody and contactin-associated protein 2 (Caspr2, can result in profound insomnia and other sleep disorders. Central neurogenic hypoventilation are found in patients with anti-N-methyl-D-aspartate (NMDA receptor encephalitis, whereas obstructive sleep apnea (OSA, stridor and parasomnia are prominent features of encephalopathy associated with IgLON5 antibodies. Sleep disorders are cardinal manifestations in patients with autoimmune encephalitis. Immunotherapy possiblely can improve clinical symptoms and prognosis in a positive way. DOI: 10.3969/j.issn.1672-6731.2017.10.004

  17. Molecular mechanisms of neuroinflammation and injury during acute viral encephalitis.

    Science.gov (United States)

    Shives, Katherine D; Tyler, Kenneth L; Beckham, J David

    2017-07-15

    Viral infections in the central nervous system are a major cause of encephalitis. West Nile virus (WNV) and Herpes simplex virus (HSV) are the most common causes of viral encephalitis in the United States. We review the role of neuroinflammation in the pathogenesis of WNV and HSV infections in the central nervous system (CNS). We discuss the role of the innate and cell-mediated immune responses in peripheral control of viral infection, viral invasion of the CNS, and in inflammatory-mediated neuronal injury. By understanding the role of specific inflammatory responses to viral infections in the CNS, targeted therapeutic approaches can be developed to maximize control of acute viral infection while minimizing neuronal injury in the CNS. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Encefalitis carcinomatosa Carcinomatous encephalitis

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    Flavio Sánchez

    2004-12-01

    Full Text Available Se comunica un caso de encefalitis carcinomatosa, en un paciente con diagnóstico de adenocarcinoma de pulmón y síndrome confusional. Esta entidad es poco conocida en relación a otras afecciones neurológicas relacionadas al cáncer. Se discute su presentación clínica, se destaca la necesidad de sospecharla aun luego de obtener una tomografía computada normal y sus típicas imágenes miliares en resonancia magnética.We report a case of carcinomatous encephalitis in a patient with lung adenocarcinoma and confusional syndrome. This is a rare form of brain metastases. We discuss its clinical picture, the importance of suspecting it after a normal computed tomography scan and the miliary typical images at magnetic resonance.

  19. Vesicular stomatitis virus (indiana 2 serotype as experimental model to study acute encephalitis – morphological features Vírus da estomatite vesicular (sorotipo indiana 2 como modelo experimental para o estudo de encefalite aguda – aspectos morfológicos

    Directory of Open Access Journals (Sweden)

    Florêncio Figueiredo Cavalcanti Neto

    2003-10-01

    Full Text Available The Vesicular Stomatitis Virus (VSV is a Vesiculovirus of the Rhabdoviridae family that infects mammals and causes vesicular lesions similar to those of foot-and-mouth disease. VSV experimental encephalitis can be induced in rodents and the symptoms are similar to those observed in rabies. However, the lesions observed in the animals´ encephalon are different. Inclusion bodies are not observed. There is necrosis, particularly in the region of the olfactory bulb, and, in some cases, ventriculitis. It was observed that the time pattern of VSV dissemination and the morphological aspects of the lesions are similar to those described in literature. The virus seems to be disseminated through the brain ventricles, being multiplied in the ependyma cells and in the neurons, besides using retrograde and anterograde transport. It was noticed that, due to the facility of virus manipulation, this experimental model has been used in innumerable research studies in several fields. If, on the one hand there are plenty of reports on the infection pathogenesis, on the other hand there are many gaps involving, for instance, aspects about virus transmission, recovery of infected animals and participation of glial cells in the acute as well as in the recovery phases.   O vírus da estomatite vesicular (VEV é um Vesiculovírus da família Rhabdoviridae que infecta mamíferos e causa lesões vesiculares semelhantes às observadas na febre aftosa. A encefalite experimental pode ser induzida em roedores e os sintomas são semelhantes aos observados na raiva; entretanto, as lesões observadas no encéfalo dos animais são diferentes. Corpúsculos de inclusão não são observados, há necrose especialmente da região do bulbo olfatório e em alguns casos, ventriculite. Observamos que o padrão temporal de disseminação do VEV e os aspectos morfológicos das lesões são similares aos descritos na literatura. O vírus parece se disseminar através dos ventr

  20. Tick-borne encephalitis: A review of epidemiology, clinical characteristics, and management.

    Science.gov (United States)

    Bogovic, Petra; Strle, Franc

    2015-05-16

    Tick-borne encephalitis is an infection of central nervous system caused by tick-borne encephalitis virus transmitted to humans predominantly by tick bites. During the last few decades the incidence of the disease has been increasing and poses a growing health problem in almost all endemic European and Asian countries. Most cases occur during the highest period of tick activity, in Central Europe mainly from April to November. Tick-borne encephalitis is more common in adults than in children. Clinical spectrum of the disease ranges from mild meningitis to severe meningoencephalitis with or without paralysis. Rare clinical manifestations are an abortive form of the disease and a chronic progressive form. A post-encephalitic syndrome, causing long-lasting morbidity that often affects the quality of life develops in up to 50% of patients after acute tick-borne encephalitis. Clinical course and outcome vary by subtype of tick-borne encephalitis virus (the disease caused by the European subtype has milder course and better outcome than the disease caused by Siberian and Far-Easter subtypes), age of patients (increasing age is associated with less favorable outcome), and host genetic factors. Since clinical features and laboratory results of blood and cerebrospinal fluid are nonspecific, the diagnosis must be confirmed by microbiologic findings. The routine laboratory confirmation of the tick-borne encephalitis virus infection is based mainly on the detection of specific IgM and IgG antibodies in serum (and cerebrospinal fluid), usually by enzyme-linked immunosorbent assay. There is no specific antiviral treatment for tick-borne encephalitis. Vaccination can effectively prevent the disease and is indicated for persons living in or visiting tick-borne encephalitis endemic areas.

  1. Acyclovir-resistant herpes simplex encephalitis in a patient treated with anti-tumor necrosis factor-α monoclonal antibodies.

    Science.gov (United States)

    Schepers, Kinda; Hernandez, Antonio; Andrei, Graciela; Gillemot, Sarah; Fiten, Pierre; Opdenakker, Ghislain; Bier, Jean-Christophe; David, Philippe; Delforge, Marie-Luce; Jacobs, Frédérique; Snoeck, Robert

    2014-01-01

    Herpes simplex virus is the most common cause of severe sporadic encephalitis. We report a case of herpes simplex type 1-encephalitis in a 50-year-old woman receiving anti-tumor necrosis factor-α monoclonal antibodies adalimumab. Although she was an acyclovir naïve patient, a mixed viral population (wild-type and acyclovir-resistant bearing a thymidine-kinase mutation) was identified in the cerebrospinal fluid. The virus in cerebrospinal fluid evolved and a second thymidine-kinase mutant virus emerged. Combined foscavir and acyclovir treatment resolved the herpes simplex encephalitis. To our knowledge, this is the first report of acyclovir-resistant herpes simplex encephalitis in a patient treated with adalimumab. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Japanese Encephalitis: Estimating Future Trends in Asia

    Directory of Open Access Journals (Sweden)

    Julia Metelka

    2015-08-01

    Full Text Available Limited surveillance programs and lack of diagnostic laboratory testing capacity in many low and middle income Asian countries have made it difficult to validate epidemiological patterns and anticipate future changes in disease risk. In this study, we consider the case of Japanese Encephalitis in Asia and examine how populations of human hosts and animal reservoirs are expected to change over the next three decades. Growth was modelled at the sub-national level for rural and urban areas to estimate where high-density, susceptible populations will potentially overlap with populations of the virus' amplifying host. High-risk areas based on these projections were compared to the current distribution of Japanese Encephalitis, and known immunization activities in order to identify areas of highest priority for concern. Results indicated that mapping JE risk factors at the sub-national level is an effective way to contextualize and supplement JE surveillance data. New patterns of risk factor change occurring in Southeast Asia were identified, including around major urban areas experiencing both urbanization and growth in pig populations. A hotspot analysis of pig-to-population ratio found a significant spatial cluster extending northward through Southeast Asia and interior China. Mapping forecasted changes in risk factors for JE highlights regions vulnerable to emerging zoonoses and may be an important tool for developing effecting transnational health policies.

  3. Eastern equine encephalitis cases among horses in Brazil between 2005 and 2009.

    Science.gov (United States)

    de Novaes Oliveira, Rafael; Iamamoto, Keila; Silva, Maria Luana Cristiny Rodrigues; Achkar, Samira Maria; Castilho, Juliana Galera; Ono, Ekaterina Durymanova; Lobo, Renata Spinelli Vaz; Brandão, Paulo Eduardo; Carnieli, Pedro; Carrieri, Maria Luiza; Kotait, Ivanete; Macedo, Carla Isabel

    2014-10-01

    Eastern equine encephalitis is a viral zoonosis that exhibits complex distribution and epidemiology, and greater importance should be given to this disease by the public-health authorities. In Brazil, although eastern equine encephalitis virus (EEEV) has been identified in vectors and antibodies are sometimes detected in horses and humans, there have been no records of equine encephalitis in horses caused by this virus during the last 24 years. This study describes eighteen cases of eastern equine encephalomyelitis that occurred in six Brazilian states between 2005 and 2009. Viral RNA was identified using semi-nested RT-PCR to detect members of the genus Alphavirus, and by genetic sequencing. The gene encoding NSP1 was partially amplified, and after genetic sequencing, eighteen sequences were generated. All eighteen strains were classified as belonging to lineage III of American EEEV. These findings could be an indication of the importance of this virus in animal and human public health.

  4. The validation of housekeeping genes as a reference in quantitative Real Time PCR analysis: application in the milk somatic cells and frozen whole blood of goats infected with caprine arthritis encephalitis virus.

    Science.gov (United States)

    Jarczak, Justyna; Kaba, Jarosław; Bagnicka, Emilia

    2014-10-10

    The validation of housekeeping genes (HKGs) for normalization of RNA expression in Real-Time PCR is crucial to obtain the most reliable results. There is limited information on reference genes used in the study of gene expression in milk somatic cells and the frozen whole blood of goats. Thus, the aim of this study was to propose the most stable housekeeping genes that can be used as a reference in Real-Time PCR analysis of milk somatic cells and whole blood of goats infected with caprine arthritis encephalitis virus (CAEV). Animals were divided into two groups: non-infected (N=13) and infected with CAEV (N=13). Biological material (milk somatic cells and whole blood) was collected 4 times during the lactation period (7, 30, 100 and 240days post-partum). The expression levels of candidate reference genes were analyzed using geNorm and NormFinder software. The stability of candidates for reference gene expression was analyzed for CAEV-free (control) and CAEV-infected groups, and also for both groups together (combined group). The stability of expression of β-actin (ACTB), glyceraldehyde-3P-dehydrogenase (GAPDH), cyclophilin A (PPIA), RNA18S1, ubiquilin (UBQLN1) and ribosomal protein large subunit P0 (RPLP0) was determined in milk somatic cells, while ACTB, PPIA, RPLP0, succinate dehydrogenase complex subunit A (SDHA), zeta polypeptide (YWHAZ), battenin (CLN3), eukaryotic translation initiation factor 3K (EIF3K) and TATA box-binding protein (TBP) were measured in frozen whole blood of goats. PPIA and RPLP0 were considered as the most suitable internal controls as they were stably expressed in milk somatic cells regardless of disease status, according to NormFinder software. Furthermore, geNorm results indicated the expression of PPIA/RPLP0 genes as the best combination under these experimental conditions. The results of frozen whole blood analysis using NormFinder software revealed that the most stable reference gene in control, CAEV-infected and combined groups is

  5. Prevalence estimation of tick-borne encephalitis virus (TBEV) antibodies in dogs from Finland using novel dog anti-TBEV IgG MAb-capture and IgG immunofluorescence assays based on recombinant TBEV subviral particles.

    Science.gov (United States)

    Levanov, Lev; Vera, Cristina Pérez; Vapalahti, Olli

    2016-07-01

    Tick-borne encephalitis (TBE) is one of the most dangerous human neurological infections occurring in Europe and Northern parts of Asia with thousands of cases and millions vaccinated against it. The risk of TBE might be assessed through analyses of the samples taken from wildlife or from animals which are in close contact with humans. Dogs have been shown to be a good sentinel species for these studies. Serological assays for diagnosis of TBE in dogs are mainly based on purified and inactivated TBEV antigens. Here we describe novel dog anti-TBEV IgG monoclonal antibody (MAb)-capture assay which is based on TBEV prME subviral particles expressed in mammalian cells from Semliki Forest virus (SFV) replicon as well as IgG immunofluorescence assay (IFA) which is based on Vero E6 cells transfected with the same SFV replicon. We further demonstrate their use in a small-scale TBEV seroprevalence study of dogs representing different regions of Finland. Altogether, 148 dog serum samples were tested by novel assays and results were compared to those obtained with a commercial IgG enzyme immunoassay (EIA), hemagglutination inhibition test and IgG IFA with TBEV infected cells. Compared to reference tests, the sensitivities of the developed assays were 90-100% and the specificities of the two assays were 100%. Analysis of the dog serum samples showed a seroprevalence of 40% on Åland Islands and 6% on Southwestern archipelago of Finland. In conclusion, a specific and sensitive EIA and IFA for the detection of IgG antibodies in canine sera were developed. Based on these assays the seroprevalence of IgG antibodies in dogs from different regions of Finland was assessed and was shown to parallel the known human disease burden as the Southwestern archipelago and Åland Islands in particular had considerable dog TBEV antibody prevalence and represent areas with high risk of TBE for humans. Copyright © 2016 Elsevier GmbH. All rights reserved.

  6. Development history of herpes simplex encephalitis

    Directory of Open Access Journals (Sweden)

    Jia-wei WANG

    2014-08-01

    Full Text Available Herpes simplex encephalitis (HSE is an acute central nervous system infection caused by herpes simplex virus (HSV. Early clinical manifestations mainly include fever, headache and unconsciousness; when progressing, psychiatric symptoms can occur. Death or serious neurological sequelae will happen if not treated. With the development of laboratory tests and imaging techniques, the early diagnosis of HSE is possible. Even though imaging with temporal lobe abnormal signal has the implication to HSE, the application of polymerase chain reaction (PCR in detecting HSV DNA in cerebrospinal fluid is currently the "gold standard" to diagnose HSE. Once diagnosed, acyclovir must be given as soon as possible, as delayed treatment will result in a poor outcome. doi: 10.3969/j.issn.1672-6731.2014.08.003

  7. Encephalitis (For Parents)

    Science.gov (United States)

    ... by ticks or of rabies spread by rabid animals. Mosquitoes can also transmit the viruses for several ... loss of sensation anywhere in the body sudden personality changes problems with memory extreme drowsiness or lethargy ...

  8. Travelers' Health: Japanese Encephalitis

    Science.gov (United States)

    ... Zika Travel Information World Map of Zika Country Classification Technical Guidance Risk of Zika Virus at Your ... Common clinical laboratory findings include moderate leukocytosis, mild anemia, and hyponatremia. Cerebrospinal fluid (CSF) typically has a ...

  9. Vírus do mosaico severo do caupi-CPSMV como molécula carreadora para a p28 do vírus da artrite-encefalite caprina-CAEV Cowpea severe mosaic virus CPSMV as a carrier molecule to p28 from caprine arthritis-encephalitis virus-CAEV

    Directory of Open Access Journals (Sweden)

    Francisco Jarbas Santos de Sousa

    2005-12-01

    Full Text Available O vírus da Artrite-encefalite caprina (CAEV pertence à família Retroviridae, gênero Lentivirus. O CAEV infecta caprinos do mundo inteiro causando artrite, encefalite, mamite, pneumonia e emagrecimento progressivo. Este trabalho mostra a formação de uma quimera construída através da mistura da p28 do CAEV com glutaraldeído e CPSMV, purificada por meio de cromatografia em biogel e sephadex G-150. As cromatografias foram monitoradas através de leituras em espectrofotômetro no comprimento de onda de 280nm, dos líquidos coletados nos tubos. Os picos contendo a quimera foram coletados e submetidos à eletroforese (SDS-PAGE, sendo assim evidenciada a banda correspondente à mesma. Grupos de camundongos swiss foram imunizados com o vírus quimérico (CPSMV + p28, com o vírus CPSMV purificado e com a proteína p28 do CAEV, utilizando o adjuvante de Freund incompleto. Os anticorpos específicos produzidos contra o CPSMV e p28 reconheceram a proteína quimérica em Western Blotting e em teste de ELISA. Os anticorpos contra o vírus quimérico apresentaram títulos mais elevados do que os anticorpos produzidos contra a p28, demonstrando que o vírus quimérico apresenta maior imunogenicidade do que a proteína p28 sozinha. Os resultados mostraram que o acoplamento covalente entre o CPSMV e a p28 do CAEV foi obtido com sucesso, originando uma molécula estável não comprometendo a estrutura do capsídeo do CPSMV. Desta forma, sugere-se que o CPSMV possa ser utilizado como molécula carreadora na produção de vacinas para vírus que infectam animais.Caprine arthritis-encephalitis virus (CAEV belongs to Retroviridae family, Lentivirus genus. This virus infects caprine all over the world causing arthritis, encephalitis, mammitis and progressive emaciating. This research showed chimera's building made by mixing up CAEV p28, with glutaraldehyde, and CPSMV, purified through the chromotography in biogel and sephadex (G-150. After that, some measures

  10. Regional impact of climate on Japanese encephalitis in areas located near the three gorges dam.

    Science.gov (United States)

    Bai, Yuntao; Xu, Zhiguang; Zhang, Jing; Mao, Deqiang; Luo, Chao; He, Yuanyuan; Liang, Guodong; Lu, Bo; Bisesi, Michael S; Sun, Qinghua; Xu, Xinyi; Yang, Weizhong; Liu, Qiyong

    2014-01-01

    In this study, we aim to identify key climatic factors that are associated with the transmission of Japanese encephalitis virus in areas located near the Three Gorges Dam, between 1997 and 2008. We identified three geographical regions of Chongqing, based on their distance from the Three Gorges Dam. Collectively, the three regions consisted of 12 districts from which study information was collected. Zero-Inflated Poisson Regression models were run to identify key climatic factors of the transmission of Japanese encephalitis virus for both the whole study area and for each individual region; linear regression models were conducted to examine the fluctuation of climatic variables over time during the construction of the Three Gorges Dam. Between 1997 and 2008, the incidence of Japanese encephalitis decreased throughout the entire city of Chongqing, with noticeable variations taking place in 2000, 2001 and 2006. The eastern region, which is closest to the Three Gorges Dam, suffered the highest incidence of Japanese encephalitis, while the western region experienced the lowest incidence. Linear regression models revealed that there were seasonal fluctuations of climatic variables during this period. Zero-Inflated Poisson Regression models indicated a significant positive association between temperature (with a lag of 1 and 3 months) and Japanese encephalitis incidence, and a significant negative association between rainfall (with a lag of 0 and 4 months) and Japanese encephalitis incidence. The spatial and temporal trends of Japanese encephalitis incidence that occurred in the City of Chongqing were associated with temperature and rainfall. Seasonal fluctuations of climatic variables during this period were also observed. Additional studies that focus on long-term data collection are needed to validate the findings of this study and to further explore the effects of the Three Gorges Dam on Japanese encephalitis and other related diseases.

  11. Regional impact of climate on Japanese encephalitis in areas located near the three gorges dam.

    Directory of Open Access Journals (Sweden)

    Yuntao Bai

    Full Text Available BACKGROUND: In this study, we aim to identify key climatic factors that are associated with the transmission of Japanese encephalitis virus in areas located near the Three Gorges Dam, between 1997 and 2008. METHODS: We identified three geographical regions of Chongqing, based on their distance from the Three Gorges Dam. Collectively, the three regions consisted of 12 districts from which study information was collected. Zero-Inflated Poisson Regression models were run to identify key climatic factors of the transmission of Japanese encephalitis virus for both the whole study area and for each individual region; linear regression models were conducted to examine the fluctuation of climatic variables over time during the construction of the Three Gorges Dam. RESULTS: Between 1997 and 2008, the incidence of Japanese encephalitis decreased throughout the entire city of Chongqing, with noticeable variations taking place in 2000, 2001 and 2006. The eastern region, which is closest to the Three Gorges Dam, suffered the highest incidence of Japanese encephalitis, while the western region experienced the lowest incidence. Linear regression models revealed that there were seasonal fluctuations of climatic variables during this period. Zero-Inflated Poisson Regression models indicated a significant positive association between temperature (with a lag of 1 and 3 months and Japanese encephalitis incidence, and a significant negative association between rainfall (with a lag of 0 and 4 months and Japanese encephalitis incidence. CONCLUSION: The spatial and temporal trends of Japanese encephalitis incidence that occurred in the City of Chongqing were associated with temperature and rainfall. Seasonal fluctuations of climatic variables during this period were also observed. Additional studies that focus on long-term data collection are needed to validate the findings of this study and to further explore the effects of the Three Gorges Dam on Japanese

  12. Prostate cancer may trigger paraneoplastic limbic encephalitis

    DEFF Research Database (Denmark)

    Jakobsen, Jakob Kristian; Zakharia, Elias Raja; Boysen, Anders Kindberg Fossø

    2013-01-01

    -Hu antibody test the patient was diagnosed with paraneoplastic limbic encephalitis related to prostate cancer. The patient died within 6 months. We review the literature on prostate cancer-related paraneoplastic limbic encephalitis. High-risk prostate cancer can trigger paraneoplastic limbic encephalitis...

  13. Infectious Disease Proteome Biomarkers: Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, Charles L.

    2011-12-31

    Research for the DOE Infectious Disease Proteome Biomarkers focused on Rift Valley fever virus (RVFV) and Venezuelan Equine Encephalitis Virus (VEEV). RVFV and VEEV are Category A and B pathogens respectively. Among the priority threats, RVFV and VEEV rank high in their potential for being weaponized and introduced to the United States, spreading quickly, and having a large health and economic impact. In addition, they both have live attenuated vaccine, which allows work to be performed at BSL-2. While the molecular biology of RVFV and VEEV are increasingly well-characterized, little is known about its host-pathogen interactions. Our research is aimed at determining critical alterations in host signaling pathways to identify therapeutics targeted against the host.

  14. Control of Japanese encephalitis in Asia: the time is now.

    Science.gov (United States)

    Hills, Susan; Martin, Rebecca; Marfin, Anthony; Fischer, Marc

    2014-08-01

    Japanese encephalitis (JE) virus is the most common vaccine-preventable cause of encephalitis in Asia. Recent progress in the development and availability of improved JE vaccines has revitalized the prospects for JE control. There now are a number of safe and effective vaccines, two WHO prequalified vaccines available for pediatric use, at least one vaccine considered affordable for use in lower income countries, and a GAVI Alliance commitment to provide financial support to eligible countries for campaigns for children aged 9 months through 14 years. While challenges remain, this tremendous progress means there is a better opportunity than at any time in the past to prevent the substantial morbidity and mortality from this disease.

  15. Is a booster dose necessary in children after immunization with live attenuated Japanese encephalitis vaccine?

    Science.gov (United States)

    Choi, Ui Yoon; Lee, Soo Young; Kim, Ki Hwan; Kim, Dong Soo; Choi, Kyong Min; Cha, Sung Ho; Kang, Jin Han

    2013-10-01

    Japanese encephalitis virus is a common cause of encephalitis in Asian children; therefore, maintenance of immunity against Japanese encephalitis virus is essential. Although many countries recommend booster vaccination, some trials have concluded that administration of one or two vaccinations is sufficient. The current study was conducted to evaluate immunogenicity and safety after a booster vaccination with live attenuated vaccine. For 68 study subjects, measurement of antibody titer was performed before and at 4-6 weeks after administration of a booster dose. Adverse reactions occurring at the injection site and systemic adverse reactions were documented. The percentages of subjects with seroprotective neutralizing antibody titers was 100% before and after booster vaccination, and the geometric mean titer increased after booster vaccination. Thus, we predict that immunity will be maintained for a long time by an amnestic response. Low percentages of adverse reactions indicated the safety of the immunizations.

  16. A large outbreak of Japanese encephalitis predominantly among adults in northern region of West Bengal, India.

    Science.gov (United States)

    Gurav, Yogesh K; Bondre, Vijay P; Tandale, Babasaheb V; Damle, Rekha G; Mallick, Sanjay; Ghosh, Uday S; Nag, Shankha S

    2016-11-01

    Unusual rise of acute encephalitis syndrome cases (AES) were reported in July 2014 in the northern region of West Bengal, India. Investigations were carried out to characterize the outbreak and to identify the associated virus etiology. This observational study is based on 398 line listed AES cases, mostly (70.8%, 282/398) adults, with case fatality ratio of 28.9% (115/398). Japanese encephalitis virus infection was detected in 134 (49.4%) among 271 AES cases tested and most of them (79.1%, 106/134) were adults. The study reports a large outbreak of genotype III Japanese encephalitis among adults in northern region of West Bengal, India. J. Med. Virol. 88:2004-2011, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Molecular characterization of two Rocio flavivirus strains isolated during the encephalitis epidemic in São Paulo State, Brazil and the development of a one-step RT-PCR assay for diagnosis.

    Science.gov (United States)

    Coimbra, Terezinha Lisieux Moraes; Santos, Raimundo N; Petrella, Selma; Nagasse-Sugahara, Teresa Keico; Castrignano, Silvana Beres; Santos, Cecília L Simões

    2008-01-01

    Rocio virus (ROCV) was responsible for an explosive encephalitis epidemic in the 1970s affecting about 1,000 residents of 20 coastland counties in São Paulo State, Brazil. ROCV was first isolated in 1975 from the cerebellum of a fatal human case of encephalitis. Clinical manifestations of the illness are similar to those described for St. Louis encephalitis. ROCV shows intense antigenic cross-reactivity with Japanese encephalitis complex (JEC) viruses, particularly with Ilheus (ILHV), St. Louis encephalitis, Murray Valley and West Nile viruses. In this study, we report a specific RT-PCR assay for ROCV diagnosis and the molecular characterization of the SPAn37630 and SPH37623 strains. Partial nucleotide sequences of NS5 and E genes determined from both strains were used in phylogenetic analysis. The results indicated that these strains are closely related to JEC viruses, but forming a distinct subclade together with ILHV, in accordance with results recently reported by Medeiros et al. (2007).

  18. Can we differentiate between herpes simplex encephalitis and Japanese encephalitis?

    Science.gov (United States)

    Kalita, Jayantee; Misra, Usha Kant; Mani, Vinita Elizabeth; Bhoi, Sanjeev Kumar

    2016-07-15

    Herpes simplex encephalitis (HSE) occurs without regional and seasonal predilections. HSE is important to differentiate from arboviral encephalitis in endemic areas because of therapeutic potential of HSE. This study evaluates clinical features, MRI and laboratory findings which may help in differentiating HSE from Japanese encephalitis (JE). Confirmed patients with JE and HSE in last 10years were included. The presenting clinical symptoms including demographic information, seizure, behavioral abnormality, focal weakness and movement disorders were noted. Cranial MRI was done and location and nature of signal alteration were noted. Electroencephalography (EEG), cerebrospinal fluid (CSF), blood counts and serum chemistry were done. Outcome was measured by modified Rankin Scale (mRS). Death, functional outcome and neurological sequelae were noted at 3, 6 and 12months follow up, and compared between HSE and JE. Outcome was categorized as poor (mRS;>2) and good (mRS≤2). 97 patients with JE and 40 HSE were included. JE patients were younger than HSE and occurred in post monsoon period whereas HSE occurred throughout the year. Seizure (86% vs 40%) and behavioral abnormality (48% vs 10%) were commoner in HSE; whereas movement disorders (76% vs 0%) and focal reflex loss (42% vs 10%) were commoner in JE. CSF findings and laboratory parameters were similar in both the groups. Thalamic involvement in JE and temporal involvement in HSE were specific markers of respective encephalitis. Delta slowing on EEG was more frequent in JE than HSE. 20% JE and 30% HSE died in the hospital, and at 1year follow up JE patients showed better outcome compared to HSE (48% vs 24%). Memory loss (72% vs 22%) was the predominant sequelae in HSE. Seizure and behavioral abnormality are common features in HSE whereas focal reflex loss is commoner in JE. In a patient with acute encephalitis, thalamic lesion suggests JE and temporal lobe involvement HSE. Long term outcome in JE is better compared to

  19. Disease: H01547 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01547 Venezuelan equine fever Venezuelan equine fever is one of the mosquito-born...e viral fevers. The disease is caused by Venezuelan equine encephalitis virus (VEEV), an alphavirus that is ...ometimes followed by death. Infectious disease ... Venezuelan equine encephalitis virus [GN:T40028] ... Serodiagn... fevers. ICD-10: A92.2 MeSH: D004685 PMID:23968890 ... AUTHORS ... Taylor KG, Paessler S ... TITLE ... Pathogenesis of Venezuela

  20. Global emergence of Zika virus

    Directory of Open Access Journals (Sweden)

    Richard Tjan

    2016-05-01

    Full Text Available Zika virus (ZIKV belongs to the flaviviruses (family Flaviviridae, which includes dengue, yellow fever, West Nile, and Japanese encephalitis viruses. Zika virus was isolated in 1947, in the Zika forest near Kampala, Uganda, from one of the rhesus monkeys used as sentinel animals in a yellow fever research program.

  1. Regulation of inflammation in Japanese encephalitis.

    Science.gov (United States)

    Lannes, Nils; Summerfield, Artur; Filgueira, Luis

    2017-08-14

    Uncontrolled inflammatory response of the central nervous system is a hallmark of severe Japanese encephalitis (JE). Although inflammation is necessary to mount an efficient immune response against virus infections, exacerbated inflammatory response is often detrimental. In this context, cells of the monocytic lineage appear to be important forces driving JE pathogenesis. Brain-infiltrating monocytes, macrophages and microglia play a major role in central nervous system (CNS) inflammation during JE. Moreover, the role of inflammatory monocytes in viral neuroinvasion during JE and mechanisms of cell entry into the CNS remains unclear. The identification of cellular and molecular actors in JE inflammatory responses may help to understand the mechanisms behind excessive inflammation and to develop therapeutics to treat JE patients. This review addresses the current knowledge about mechanisms of virus neuroinvasion, neuroinflammation and therapeutics critical for JE outcome. Understanding the regulation of inflammation in JE is challenging. Elucidation of the remaining open questions will help to the development of therapeutic approaches avoiding detrimental inflammatory responses in JE.

  2. Successful treatment with ganciclovir of presumed Epstein-Barr meningo-encephalitis following bone marrow transplant

    NARCIS (Netherlands)

    Dellemijn, P L; Brandenburg, A; Niesters, H G; van den Bent, M J; Rothbarth, P H; Vlasveld, L T

    Epstein-Barr virus-specific polymerase chain reaction was used to diagnose EBV-meningo-encephalitis in a bone marrow transplant recipient. The patient made complete recovery with ganciclovir treatment. Pitfalls in diagnosis with EBV-PCR and the potential therapeutic efficacy of ganciclovir in EBV

  3. Tick-borne encephalitis in Slovenia (1953-2013: the 60th anniversary

    Directory of Open Access Journals (Sweden)

    Slavec Zvonka Zupanič

    2014-03-01

    Full Text Available Introduction: In the year 2013, we are celebrating the 60th anniversary of the isolation of the tick-borne encephalitis virus (TBE in Slovenia. Ever since its isolation, Slovenian infectologists, epidemiologists, virologists and other experts have been researching this disease.

  4. Epstein-Barr virus and the nervous system

    NARCIS (Netherlands)

    Portegies, P.; Corssmit, N.

    2000-01-01

    The neurological complications of Epstein-Barr virus infection include viral meningitis, encephalitis and neuromuscular complications. The introduction of cerebrospinal fluid polymerase chain reaction for Epstein-Barr virus DNA has improved diagnosis of these conditions and of primary central

  5. Reducing Vulnerability to the Threat of Japanese Encephalitis in ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Extrants. Articles de revue. Comparative spatial dynamics of Japanese encephalitis and acute encephalitis syndrome in Nepal. Articles de revue. Regional variation in pig farmer awareness and actions regarding Japanese encephalitis in Nepal : implications for public health education ...

  6. PAPILLEDEMA: AN UNUSUAL FINDING IN A PATIENT WITH HERPES ENCEPHALITIS

    Directory of Open Access Journals (Sweden)

    A. Sudbakhsh

    2007-08-01

    Full Text Available Herpes simplex virus accounts for 10 to 25% of sporadic viral encephalitis throughout the world among people of different age with two peaks, one at 5 to 30 and the other at > 50 years of age. Pathologic process includes focal brain tissue inflammation and necrosis (predominantly temporal lobe. Therefore local neurological signs and symptoms will ensue. Although CSF pressure rising due to inflammation is expected, papilledema which is defined as a noninflammatory congestion of optic disk due to raised intracranial pressure has not yet been mentioned as a sign of focal encephalitis. In this article we report a 24 year-old patient with headache, fever and some degree of cognitive disorder who was definitely diagnosed (with MRI and PCR technique and treated for herpes encephalitis. Unexpectedly he had papilledema which led to more investigation. Most signs and symptoms disappeared during two weeks of intravenous acyclovir therapy as did papilledema to some extent. In this case, positive CSF PCR test for HSV confirmed the diagnosis. However it seems that along with starting acyclovir therapy, performing other supplementary studies (e.g. CT scan, MRI with and without I.V. contrast, CSF cytology and serologic tests for HIV to rule out other conditions that may be associated with papilledema and focal neurological signs (like malignancies, is mandatory.

  7. Eastern equine encephalitis in 9 South American camelids.

    Science.gov (United States)

    Nolen-Walston, Rose; Bedenice, Daniela; Rodriguez, Carlos; Rushton, Steven; Bright, Amy; Fecteau, Marie-Eve; Short, Diana; Majdalany, Ron; Tewari, Deepanker; Pedersen, Douglas; Kiupel, Matti; Maes, Roger; Del Piero, Fabio

    2007-01-01

    Eastern equine encephalitis (EEE) virus is a mosquito-borne togavirus (alphavirus) that causes severe (often fatal) encephalitis in many mammalian species, but it has not been reported previously in South American camelids. South American camelids can become naturally infected with EEE virus and show encephalitic signs similar to those observed in other affected species. Nine cases (8 alpacas and 1 llama, aged 3.5 weeks to 12 years) were identified; 4 of 9 were 510 weeks old. All cases were from the East Coast of the United States and presented in late summer and fall. A retrospective study was performed to include confirmed cases of EEE in camelids in North America before 2006. Eight of nine (89%) camelids died or were euthanized in extremis, with the mean time to death of 2 days. Clinical signs were consistent with encephalitis and included fever, lethargy, ataxia, seizures, recumbency, torticollis, opisthotonus, and vestibular signs. No consistent hematologic abnormalities were identified, and cerebrospinal fluid contained an increased protein concentration in the single camelid analyzed. No successful therapy was identified. EEE was confirmed by alphavirus detection by using immunohistochemistry (IHC) and polymerase chain reaction (PCR) in the central nervous system (CNS) and by serology. Findings included polioencephalitis with lymphocytic perivascular cuffing; neutrophil infiltration; gliosis; neuron satellitosis; necrosis; and edema, with intracytoplasmic alphavirus within neurons and glial cells. No virus was detected in extraneural tissues. In endemic areas, EEE should be considered a differential diagnosis for young and adult camelids with CNS disease. Brain histopathology with indirect IHC or PCR is diagnostic.

  8. Recent advances in Japanese encephalitis

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    Basu, Anirban; Dutta, Kallol

    2017-01-01

    Japanese encephalitis is a flaviviral disease that is endemic to the South, Southeast Asia, and Asia Oceania regions. Given that about 60% of the world’s population (about 7.4 billion) resides in this region (about 4.4 billion), this disease poses a significant threat to global health. Active vaccination campaigns conducted in endemic countries have led to a decrease in the number of reported cases over the years. In this article, we strive to briefly highlight recent advances in understanding the role of microRNAs in disease pathology, focus on providing brief summaries of recent clinical trials in the field of Japanese encephalitis therapeutics, and review the current prophylactic strategies. PMID:28357054

  9. Viral etiology of encephalitis in children in southern Vietnam: results of a one-year prospective descriptive study.

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    Van Tan Le

    2010-10-01

    Full Text Available Acute encephalitis is an important and severe disease in children in Vietnam. However, little is known about the etiology while such knowledge is essential for optimal prevention and treatment. To identify viral causes of encephalitis, in 2004 we conducted a one-year descriptive study at Children's Hospital Number One, a referral hospital for children in southern Vietnam including Ho Chi Minh City.Children less than 16 years of age presenting with acute encephalitis of presumed viral etiology were enrolled. Diagnostic efforts included viral culture, serology and real time (RT-PCRs. A confirmed or probable viral causative agent was established in 41% of 194 enrolled patients. The most commonly diagnosed causative agent was Japanese encephalitis virus (n = 50, 26%, followed by enteroviruses (n = 18, 9.3%, dengue virus (n = 9, 4.6%, herpes simplex virus (n = 1, cytomegalovirus (n = 1 and influenza A virus (n = 1. Fifty-seven (29% children died acutely. Fatal outcome was independently associated with patient age and Glasgow Coma Scale (GCS on admission.Acute encephalitis in children in southern Vietnam is associated with high mortality. Although the etiology remains unknown in a majority of the patients, the result from the present study may be useful for future design of treatment and prevention strategies of the disease. The recognition of GCS and age as predictive factors may be helpful for clinicians in managing the patient.

  10. CT of neonatal herpes encephalitis.

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    Herman, T E; Cleveland, R H; Kushner, D C; Taveras, J M

    1985-01-01

    Seven neonates with proven herpes (HSV type 2) encephalitis exhibited a characteristic sequence of findings on cranial computed tomography (CT). The initial CT abnormalities in all infants were fingerlike areas of cortical increased attenuation noted on unenhanced scans obtained 2-30 days after presentation. These usually were accentuated by increased white-matter lucency. Subsequently (more than 30 days after presentation), extensive cerebral destruction, multicystic encephalomalacia, and calcification were seen on follow-up CT scans obtained in five infants.

  11. Herpes Simplex Encephalitis Complicated by Cerebral Hemorrhage during Acyclovir Therapy.

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    Harada, Yukinori; Hara, Yuuta

    2017-01-01

    Herpes simplex encephalitis (HSE) can be complicated by adverse events in the acute phase. We herein present the case of a 71-year-old woman with HSE complicated by cerebral hemorrhage. She presented with acute deterioration of consciousness and fever and was diagnosed with HSE based on the detection of herpes simplex virus-1 in the cerebrospinal fluid by a polymerase chain reaction. The cerebral hemorrhage developed during acyclovir therapy; however, its diagnosis was delayed for 2 days. After the conservative treatment of the cerebral hemorrhage, the patient made a near-complete recovery. Cerebral hemorrhage should be considered as an acute-phase complication of HSE.

  12. Computed tomography (CT) in children with herpes simplex encephalitis

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    Taccone, A.; Gambaro, G.; Ghiorzi, M.; Fondelli, P.; Ferrea, G.; Gianbartolomei, G.; Rolando, S.

    1988-11-01

    Computed Tomography (CT) scans were obtained from nine infants with herpes simplex virus encephalitis (HSE). The early CT findings were generalized or localized edematous change and a mass effect was also seen in two cases. In the follow-up study two patients showed bilateral gyriform calcification, a rare occurrence in association with intracranial infection. The appearance of multicystic encephalomalacia was evident in one patient 3 months after the onset of disease. It is shown that the CT findings of neonates and young children with HSE are different from those of adults.

  13. Computed tomography (CT) in children with herpes simplex encephalitis.

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    Taccone, A; Gambaro, G; Ghiorzi, M; Ferrea, G; Gianbartolomei, G; Rolando, S; Fondelli, P

    1988-01-01

    Computed Tomography (CT) scans were obtained from nine infants with herpes simplex virus encephalitis (HSE). The early CT findings were generalized or localized edematous change and a mass effect was also seen in two cases. In the follow-up study two patients showed bilateral gyriform calcification, a rare occurrence in association with intracranial infection. The appearance of multicystic encephalomalacia was evident in one patient 3 months after the onset of disease. It is shown that the CT findings of neonates and young children with HSE are different from those of adults.

  14. Defining the chemokine basis for leukocyte recruitment during viral encephalitis.

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    Michlmayr, Daniela; McKimmie, Clive S; Pingen, Marieke; Haxton, Ben; Mansfield, Karen; Johnson, Nicholas; Fooks, Anthony R; Graham, Gerard J

    2014-09-01

    The encephalitic response to viral infection requires local chemokine production and the ensuing recruitment of immune and inflammatory leukocytes. Accordingly, chemokine receptors present themselves as plausible therapeutic targets for drugs aimed at limiting encephalitic responses. However, it remains unclear which chemokines are central to this process and whether leukocyte recruitment is important for limiting viral proliferation and survival in the brain or whether it is predominantly a driver of coincident inflammatory pathogenesis. Here we examine chemokine expression and leukocyte recruitment in the context of avirulent and virulent Semliki Forest virus (SFV) as well as West Nile virus infection and demonstrate rapid and robust expression of a variety of inflammatory CC and CXC chemokines in all models. On this basis, we define a chemokine axis involved in leukocyte recruitment to the encephalitic brain during SFV infection. CXCR3 is the most active; CCR2 is also active but less so, and CCR5 plays only a modest role in leukocyte recruitment. Importantly, inhibition of each of these receptors individually and the resulting suppression of leukocyte recruitment to the infected brain have no effect on viral titer or survival following infection with a virulent SFV strain. In contrast, simultaneous blockade of CXCR3 and CCR2 results in significantly reduced mortality in response to virulent SFV infection. In summary, therefore, our data provide an unprecedented level of insight into chemokine orchestration of leukocyte recruitment in viral encephalitis. Our data also highlight CXCR3 and CCR2 as possible therapeutic targets for limiting inflammatory damage in response to viral infection of the brain. Brain inflammation (encephalitis) in response to viral infection can lead to severe illness and even death. This therefore represents an important clinical problem and one that requires the development of new therapeutic approaches. Central to the pathogenesis of

  15. Herpes encephalitis during pregnancy: a case report of maternal death

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    Leila Pourali

    2016-04-01

    Full Text Available Background: Herpes encephalitis is the most common cause of fatal encephalitis in the world which often presents with sudden fever, headache, seizure, focal neurologic symptoms, and consciousness loss. The aim of this study was to report a case of maternal death caused by herpes encephalitis which appropriate antibiotic therapy delayed because of early diagnosis of eclampsia. Case Presentation: A 16-year-old pregnant woman at 36th weeks of gestation was referred to gynecology emergency department of Ghaem Hospital, Mashhad University of Medical Sciences in 2016. She was admitted due to 4 times of generalized tonic-clonic seizures and blood pressure of 140/90 mmHg with diagnosis of eclampsia. Cesarean section was performed for fetal distress and eclampsia remote from delivery. 6 hours after cesarean section because of higher than 39 °C and reduction in consciousness status, she was transferred to intensive care unit (ICU. The first brain magnetic resonance imaging (MRI was normal. Lumbar puncture (LP was performed and brain MRI was repeated that increased signal was observed in two sides of basal ganglia. Intravenous acyclovir was administered by possible diagnosis of viral meningoencephalitis. Cerebrospinal fluid (CSF was positive in terms of herpes simplex virus type 1 (HSV-1. Unfortunately, the patient died 35 days after hospitalization by diagnosis of HSV-1 encephalitis and bilateral infarction with frequent seizures and clinical manifestation of septic shock refractory to treatment. Conclusion: Although the first diagnosis for generalized convulsion during pregnancy is eclampsia, but in case of recurrent and specially atypical seizures and low consciousness level, other diagnosis like meningoencephalitis, brain lesions and cavernous sinus thrombosis (CVT must be considered and ruled out.

  16. Newly recognized mosquito-associated viruses in mainland China, in the last two decades

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    Liang Guodong

    2011-02-01

    Full Text Available Abstract There are four principal arboviruses in mainland China. Two kinds of them are mosquito-borne viruses, namely Japanese encephalitis virus and dengue virus, which lead to Japanese encephalitis, and dengue fever/dengue hemorrhagic fever respectively; the other two are tick-borne viruses, namely tick-borne encephalitis virus and Crimean-Congo hemorrhagic fever virus (also known as Xinjiang hemorrhagic fever virus, which contribute to tick-borne encephalitis and Xinjiang hemorrhagic fever respectively. With exception of these four main arboviruses, many other mosquito-associated viruses have been isolated and identified in recent years. These newly isolated and identified mosquito-associated viruses are probably responsible for human and animal infections and diseases. The purpose of this review is to describe the newly isolated mosquito-associated viruses in mainland China which belong to five viral families, including their virological properties, phylogenetic relationships, serological evidence, as well as to appeal the public health concentration worldwide.

  17. Cluster analysis for identifying sub-groups and selecting potential discriminatory variables in human encephalitis

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    Crowcroft Natasha S

    2010-12-01

    . These similarities and/or differences with respect to symptom and diagnostic measurements might be attributed to host factors. The idea that characteristics of the host may be more important than the pathogen is also consistent with the observation that for some causes, such as herpes simplex virus (HSV, encephalitis is a rare outcome of a common infection.

  18. Herpetic brainstem encephalitis: report of a post-mortem case studied electron microscopically and immunohisiochemically

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    José Eymard Homem Pitella

    1987-03-01

    Full Text Available A post-mortem examined case of herpetic brainstem encephalitis is presented. Clinically, the patient had cephalea followed by ataxia, drowsiness and multiple palsies of some cranial nerves, developing into death in eight days. The pathologic examination of the brain showed necrotizing encephalitis in multiple foci limited to the brainstem, more distinctly in the pons and medula oblongata. The technique of immunoperoxidase revealed rare glial cells with intranuclear immunoreactivity for herpes antigen. Rare viral particles with the morphological characteristics of the herpesvirus were identified in the nuclei of neurons in 10% formol fixed material. This is the second reported case of herpetic brainstem encephalitis confirmed by post-mortem examination. The pathway used by the virus to reach the central nervous system and its posterior dissemination to the oral cavity, the orbitofrontal region and the temporal lobes as well as to the brainstem, after a period of latency and reactivation, are discussed.

  19. Disseminated Herpes Zoster with Meningo-encephalitis

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    R A Bumb

    1989-01-01

    Full Text Available A 65 year old, immunocompetent, male patient developed herpes zoster ophthalmicus associated with a generalized varicellifform euption and meningo-encephalitis. Meningo-encephalitis was diagnosed on the basis of CSF picture. The patient responded in seven clays to oral acyclovir (400 mg five times a day

  20. A successfully treated case of herpes simplex encephalitis complicated by subarachnoid bleeding: a case report

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    Okuchi Kazuo

    2010-09-01

    Full Text Available Abstract Introduction Histopathologically, herpes simplex virus type 1 causes hemorrhagic necrosis. Overt hemorrhage is infrequent in herpes simplex virus encephalitis but can lead to poor outcomes. This report describes a successfully treated case of herpes simplex virus encephalitis associated with subarachnoid bleeding in which real-time polymerase chain reaction was useful for diagnosis. Case presentation A 30-year-old previously healthy Japanese woman who had fever and headache for five days presented with disorganised speech, unusual behavior and delusional thinking. Real-time polymerase chain reaction amplification of herpes simplex virus type 1 in cerebrospinal fluid was positive (38,000 copies/mL and antivirus treatment was started. During the course of her illness, the level of her consciousness decreased in association with desaturation and tachycardia. Thrombosis of the right pulmonary artery trunk with pulmonary embolism was evident on enhanced chest computed tomography. In addition, cranial computed tomography revealed subarachnoid and intraventricular bleeding. Intravenous heparin (12,000 U/day was started and the dose was adjusted according to the activated partial thromboplastin time for about a month (maximum dose of heparin, 20,400 U/day. After the treatments, her Glasgow coma score increased and the thrombosis of the pulmonary artery trunk had disappeared. Conclusions The present case raises the question of whether anticoagulant treatment is safe in patients with herpes simplex virus encephalitis complicated by subarachnoid bleeding.