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Sample records for early-life viral infection

  1. Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice

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    Asquith Kelly L

    2010-02-01

    Full Text Available Abstract Background Early-life respiratory viral infections, notably with respiratory syncytial virus (RSV, increase the risk of subsequent development of childhood asthma. The purpose of this study was to assess whether early-life infection with a species-specific model of RSV and subsequent allergen exposure predisposed to the development of features of asthma. Methods We employed a unique combination of animal models in which BALB/c mice were neonatally infected with pneumonia virus of mice (PVM, which replicates severe RSV disease in human infants and following recovery, were intranasally sensitised with ovalbumin. Animals received low-level challenge with aerosolised antigen for 4 weeks to elicit changes of chronic asthma, followed by a single moderate-level challenge to induce an exacerbation of inflammation. We then assessed airway inflammation, epithelial changes characteristic of remodelling, airway hyperresponsiveness (AHR and host immunological responses. Results Allergic airway inflammation, including recruitment of eosinophils, was prominent only in animals that had recovered from neonatal infection with PVM and then been sensitised and chronically challenged with antigen. Furthermore, only these mice exhibited an augmented Th2-biased immune response, including elevated serum levels of anti-ovalbumin IgE and IgG1 as well as increased relative expression of Th2-associated cytokines IL-4, IL-5 and IL-13. By comparison, development of AHR and mucous cell change were associated with recovery from PVM infection, regardless of subsequent allergen challenge. Increased expression of IL-25, which could contribute to induction of a Th2 response, was demonstrable in the lung following PVM infection. Signalling via the IL-4 receptor α chain was crucial to the development of allergic inflammation, mucous cell change and AHR, because all of these were absent in receptor-deficient mice. In contrast, changes of remodelling were evident in mice

  2. Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

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    Feldman, Amy S.; He, Yuan; Moore, Martin L.; Hershenson, Marc B.

    2015-01-01

    A first step in primary disease prevention is identifying common, modifiable risk factors that contribute to a significant proportion of disease development. Infant respiratory viral infection and childhood asthma are the most common acute and chronic diseases of childhood, respectively. Common clinical features and links between these diseases have long been recognized, with early-life respiratory syncytial virus (RSV) and rhinovirus (RV) lower respiratory tract infections (LRTIs) being strongly associated with increased asthma risk. However, there has long been debate over the role of these respiratory viruses in asthma inception. In this article, we systematically review the evidence linking early-life RSV and RV LRTIs with asthma inception and whether they could therefore be targets for primary prevention efforts. PMID:25369458

  3. Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity.

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    Katja Pfafferott

    2011-02-01

    Full Text Available Cellular immune responses during acute Hepatitis C virus (HCV and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%. The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution. These results were compared to the pattern of viral evolution observed in 98 subjects during a similar phase in HIV infection from a previous study. In contrast to HCV, evolution during acute HIV infection is marked by high levels of amino acid change relative to silent substitutions, including a higher proportion of adaptations, likely reflecting strong and continued CD8+ T-cell pressure combined with greater plasticity of the virus. Understanding viral escape dynamics for these two viruses is important for effective T cell vaccine design.

  4. Early age at time of primary Epstein-Barr virus infection results in poorly controlled viral infection in infants from Western Kenya: clues to the etiology of endemic Burkitt lymphoma.

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    Piriou, Erwan; Asito, Amolo S; Sumba, Peter O; Fiore, Nancy; Middeldorp, Jaap M; Moormann, Ann M; Ploutz-Snyder, Robert; Rochford, Rosemary

    2012-03-15

    Infection with Epstein-Barr virus (EBV) early in life and repeated malaria exposure have been proposed as risk factors for endemic Burkitt lymphoma (eBL). Infants were enrolled from 2 rural sites in Kenya: the Kisumu District, where malaria transmission is holoendemic and risk for eBL is high, and the Nandi District, where malaria transmission is limited and the risk for eBL is low. Blood samples were taken from infants through 2 years of age to measure EBV viral load, EBV antibodies, and malaria parasitemia. We observed a significantly younger age at time of primary EBV infection in children from Kisumu compared with children from Nandi (mean age, 7.28 months [±0.33 SEM] in Kisumu vs 8.39 months [±0.26 SEM] in Nandi), with 35.3% of children in Kisumu infected before 6 months of age. To analyze how different predictors affected EBV viral load over time, we performed multilevel mixed modeling. This modeling revealed that residence in Kisumu and younger age at first EBV infection were significant predictors for having a higher EBV viral load throughout the period of observation. Children from a region at high risk for eBL were infected very early in life with EBV, resulting in higher viral loads throughout infancy.

  5. Plum Pox Virus 6K1 Protein Is Required for Viral Replication and Targets the Viral Replication Complex at the Early Stage of Infection.

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    Cui, Hongguang; Wang, Aiming

    2016-05-15

    The potyviral RNA genome encodes two polyproteins that are proteolytically processed by three viral protease domains into 11 mature proteins. Extensive molecular studies have identified functions for the majority of the viral proteins. For example, 6K2, one of the two smallest potyviral proteins, is an integral membrane protein and induces the endoplasmic reticulum (ER)-originated replication vesicles that target the chloroplast for robust viral replication. However, the functional role of 6K1, the other smallest protein, remains uncharacterized. In this study, we developed a series of recombinant full-length viral cDNA clones derived from a Canadian Plum pox virus (PPV) isolate. We found that deletion of any of the short motifs of 6K1 (each of which ranged from 5 to 13 amino acids), most of the 6K1 sequence (but with the conserved sequence of the cleavage sites being retained), or all of the 6K1 sequence in the PPV infectious clone abolished viral replication. The trans expression of 6K1 or the cis expression of a dislocated 6K1 failed to rescue the loss-of-replication phenotype, suggesting the temporal and spatial requirement of 6K1 for viral replication. Disruption of the N- or C-terminal cleavage site of 6K1, which prevented the release of 6K1 from the polyprotein, either partially or completely inhibited viral replication, suggesting the functional importance of the mature 6K1. We further found that green fluorescent protein-tagged 6K1 formed punctate inclusions at the viral early infection stage and colocalized with chloroplast-bound viral replicase elements 6K2 and NIb. Taken together, our results suggest that 6K1 is required for viral replication and is an important viral element of the viral replication complex at the early infection stage. Potyviruses account for more than 30% of known plant viruses and consist of many agriculturally important viruses. The genomes of potyviruses encode two polyproteins that are proteolytically processed into 11 mature

  6. Targeted and Untargeted Lipidomics of Emiliania huxleyi Viral Infection and Life Cycle Phases Highlights Molecular Biomarkers of Infection, Susceptibility, and Ploidy

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    Jonathan Eliott Hunter

    2015-10-01

    Full Text Available Marine viruses that infect phytoplankton strongly influence the ecology and evolution of their hosts. Emiliania huxleyi is characterized by a biphasic life cycle composed of a diploid (2N and haploid (1N phase; diploid cells are susceptible to infection by specific coccolithoviruses, yet haploid cells are resistant. Glycosphingolipids (GSLs play a role during infection, but their molecular distribution in haploid cells is unknown. We present mass spectrometric analyses of lipids from cultures of uninfected diploid, infected diploid, and uninfected haploid E. huxleyi. Known viral GSLs were present in the infected diploid cultures as expected, but surprisingly, trace amounts of viral GSLs were also detected in the uninfected haploid cells. Sialic-acid GSLs have been linked to viral susceptibility in diploid cells, but were found to be absent in the haploid cultures, suggesting a mechanism of haploid resistance to infection. Additional untargeted high-resolution mass spectrometry data processed via multivariate analysis unveiled a number of novel biomarkers of infected, non-infected, and haploid cells. These data expand our understanding on the dynamics of lipid metabolism during E. huxleyi host/virus interactions and highlight potential novel biomarkers for infection, susceptibility, and ploidy.

  7. Life cycle synchronization is a viral drug resistance mechanism.

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    Iulia A Neagu

    2018-02-01

    Full Text Available Viral infections are one of the major causes of death worldwide, with HIV infection alone resulting in over 1.2 million casualties per year. Antiviral drugs are now being administered for a variety of viral infections, including HIV, hepatitis B and C, and influenza. These therapies target a specific phase of the virus's life cycle, yet their ultimate success depends on a variety of factors, such as adherence to a prescribed regimen and the emergence of viral drug resistance. The epidemiology and evolution of drug resistance have been extensively characterized, and it is generally assumed that drug resistance arises from mutations that alter the virus's susceptibility to the direct action of the drug. In this paper, we consider the possibility that a virus population can evolve towards synchronizing its life cycle with the pattern of drug therapy. The periodicity of the drug treatment could then allow for a virus strain whose life cycle length is a multiple of the dosing interval to replicate only when the concentration of the drug is lowest. This process, referred to as "drug tolerance by synchronization", could allow the virus population to maximize its overall fitness without having to alter drug binding or complete its life cycle in the drug's presence. We use mathematical models and stochastic simulations to show that life cycle synchronization can indeed be a mechanism of viral drug tolerance. We show that this effect is more likely to occur when the variability in both viral life cycle and drug dose timing are low. More generally, we find that in the presence of periodic drug levels, time-averaged calculations of viral fitness do not accurately predict drug levels needed to eradicate infection, even if there is no synchronization. We derive an analytical expression for viral fitness that is sufficient to explain the drug-pattern-dependent survival of strains with any life cycle length. We discuss the implications of these findings for

  8. Perinatal HIV-infection in Sankt Petersburg and Modern Therapy Concomitant Viral Infections

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    V. N. Timchenko

    2016-01-01

    Full Text Available The study included 338 HIV-infected children (B-23 and 350 children with perinatal contact HIV infection (R-75, consisting on the dispensary in the department of maternal and child the St. Petersburg City AIDS Center. In 32 persons (9.5% diagnosed with secondary infections. In the structure of viral opportunistic infections (herpesvirus, SARS amounted to 39.8%, bacterial (bronchitis, tonsillitis, pyoderma, tuberculosis — 34.8%, fungal and parasitic (candidiasis of the oral mucosa, PCP — 25.4 %. Combined therapy (causal, pathogenetic, symptomatic SARS in children with B-23 and R-75, allows you to get in early (6th d. Treatment regress the main symptoms of acute respiratory diseases. Modern therapy of congenital cytomegalovirus infection (VTSMI in children with B-23 and R-75 of the first year of life with antitsitomegalovirusnogo immunoglobulin and preparation of human recombinant interferon alfa-2b in the form of rectal suppositories — VIFERON, causes persistent normalization of clinical and laboratory parameters.

  9. [Respiratory viral infections in a cohort of children during the first year of life and their role in the development of wheezing].

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    Calvo, Cristina; Aguado, Isabel; García-García, María Luz; Ruiz-Chercoles, Esther; Díaz-Martinez, Eloisa; Albañil, Rosa María; Campelo, Olga; Olivas, Antonio; Muñóz-Gonzalez, Luisa; Pozo, Francisco; Fernandez-Arroyo, Rosa; Fernandez-Rincón, Adelaida; Calderon, Ana; Casas, Inmaculada

    2017-08-01

    It is known that infants with viral respiratory infections severe enough to require hospital admission have a high risk of developing recurrent wheezing. Few data have been published on unselected populations. The main aim of this study was to analyse symptomatic and asymptomatic respiratory viral infections during the first year of life in a cohort of infants, recruited at birth, and the development of recurrent wheezing. A total of 302 newborns were recruited. A nasopharyngeal aspirate was taken when the patients had a respiratory infection, as well as in the visits for vaccination at 2, 4, 6, and 12 months. RT-nested PCR assays were performed to detect 16 viruses. A total of 1,293 samples were analysed (1,005 healthy controls and 288 respiratory infections). Samples taken during routine check-ups were positive in 30.8% of cases, while those with respiratory infection were positive in 77.8%, P<.001 (OR: 3, 95% CI: 2.4-3.8). A total of 239 (79%) infants had at least 1 positive respiratory viral infection detected. The most frequent virus (71%) was rhinovirus (RV). Recurrent wheezing was found in 27 (11%) children during their first year of life (1.2 episodes, SD 2.9). Recurrent wheezing was present in 58.3% of patients admitted to hospital during their first viral infection, vs. 8.6% of infants when the first infection was mild or who had asymptomatic viral detection, P<.001 (OR: 2.18; 95% CI: 1.05-4.5). In our series, severe respiratory infections leading to hospitalisation in the first months of life are risk factors for developing wheezing, but not in the case of mild RV infections. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Early-life rotavirus and norovirus infections in relation to development of atopic manifestation in infants

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    Reimerink, J.; Stelma, F.; Rockx, B.; Brouwer, D.; Stobberingh, E.; van Ree, R.; Dompeling, E.; Mommers, M.; Thijs, C.; Koopmans, M.

    2009-01-01

    Summary Background The increase in incidence of atopic diseases (ADs) in the developed world over the past decades has been associated with reduced exposure of childhood infections. Objective To investigate the relation between early intestinal viral infections in relation to the development of

  11. Early-life rotavirus and norovirus infections in relation to development of atopic manifestation in infants.

    NARCIS (Netherlands)

    Reimerink, J.; Stelma, F.F.; Rockx, B.; Brouwer, D.; Stobberingh, E.E.; Ree, R. van; Dompeling, E.; Mommers, M.; Thijs, C.; Koopmans, M.

    2009-01-01

    BACKGROUND: The increase in incidence of atopic diseases (ADs) in the developed world over the past decades has been associated with reduced exposure of childhood infections. OBJECTIVE: To investigate the relation between early intestinal viral infections in relation to the development of atopic

  12. Wolbachia Blocks Viral Genome Replication Early in Infection without a Transcriptional Response by the Endosymbiont or Host Small RNA Pathways.

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    Stephanie M Rainey

    2016-04-01

    Full Text Available The intracellular endosymbiotic bacterium Wolbachia can protect insects against viral infection, and is being introduced into mosquito populations in the wild to block the transmission of arboviruses that infect humans and are a major public health concern. To investigate the mechanisms underlying this antiviral protection, we have developed a new model system combining Wolbachia-infected Drosophila melanogaster cell culture with the model mosquito-borne Semliki Forest virus (SFV; Togaviridae, Alphavirus. Wolbachia provides strong antiviral protection rapidly after infection, suggesting that an early stage post-infection is being blocked. Wolbachia does appear to have major effects on events distinct from entry, assembly or exit as it inhibits the replication of an SFV replicon transfected into the cells. Furthermore, it causes a far greater reduction in the expression of proteins from the 3' open reading frame than the 5' non-structural protein open reading frame, indicating that it is blocking the replication of viral RNA. Further to this separation of the replicase proteins and viral RNA in transreplication assays shows that uncoupling of viral RNA and replicase proteins does not overcome Wolbachia's antiviral activity. This further suggests that replicative processes are disrupted, such as translation or replication, by Wolbachia infection. This may occur by Wolbachia mounting an active antiviral response, but the virus did not cause any transcriptional response by the bacterium, suggesting that this is not the case. Host microRNAs (miRNAs have been implicated in protection, but again we found that host cell miRNA expression was unaffected by the bacterium and neither do our findings suggest any involvement of the antiviral siRNA pathway. We conclude that Wolbachia may directly interfere with early events in virus replication such as translation of incoming viral RNA or RNA transcription, and this likely involves an intrinsic (as opposed to

  13. [Emergent viral infections

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    Galama, J.M.D.

    2001-01-01

    The emergence and re-emergence of viral infections is an ongoing process. Large-scale vaccination programmes led to the eradication or control of some viral infections in the last century, but new viruses are always emerging. Increased travel is leading to a rise in the importation of exotic

  14. Dengue viral infections

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    Gurugama Padmalal

    2010-01-01

    Full Text Available Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections.

  15. EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription.

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    Kevin Tsai

    2011-11-01

    Full Text Available Productive infection by herpesviruses involve the disabling of host-cell intrinsic defenses by viral encoded tegument proteins. Epstein-Barr Virus (EBV typically establishes a non-productive, latent infection and it remains unclear how it confronts the host-cell intrinsic defenses that restrict viral gene expression. Here, we show that the EBV major tegument protein BNRF1 targets host-cell intrinsic defense proteins and promotes viral early gene activation. Specifically, we demonstrate that BNRF1 interacts with the host nuclear protein Daxx at PML nuclear bodies (PML-NBs and disrupts the formation of the Daxx-ATRX chromatin remodeling complex. We mapped the Daxx interaction domain on BNRF1, and show that this domain is important for supporting EBV primary infection. Through reverse transcription PCR and infection assays, we show that BNRF1 supports viral gene expression upon early infection, and that this function is dependent on the Daxx-interaction domain. Lastly, we show that knockdown of Daxx and ATRX induces reactivation of EBV from latently infected lymphoblastoid cell lines (LCLs, suggesting that Daxx and ATRX play a role in the regulation of viral chromatin. Taken together, our data demonstrate an important role of BNRF1 in supporting EBV early infection by interacting with Daxx and ATRX; and suggest that tegument disruption of PML-NB-associated antiviral resistances is a universal requirement for herpesvirus infection in the nucleus.

  16. EBV Tegument Protein BNRF1 Disrupts DAXX-ATRX to Activate Viral Early Gene Transcription

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    Tsai, Kevin; Thikmyanova, Nadezhda; Wojcechowskyj, Jason A.; Delecluse, Henri-Jacques; Lieberman, Paul M.

    2011-01-01

    Productive infection by herpesviruses involve the disabling of host-cell intrinsic defenses by viral encoded tegument proteins. Epstein-Barr Virus (EBV) typically establishes a non-productive, latent infection and it remains unclear how it confronts the host-cell intrinsic defenses that restrict viral gene expression. Here, we show that the EBV major tegument protein BNRF1 targets host-cell intrinsic defense proteins and promotes viral early gene activation. Specifically, we demonstrate that BNRF1 interacts with the host nuclear protein Daxx at PML nuclear bodies (PML-NBs) and disrupts the formation of the Daxx-ATRX chromatin remodeling complex. We mapped the Daxx interaction domain on BNRF1, and show that this domain is important for supporting EBV primary infection. Through reverse transcription PCR and infection assays, we show that BNRF1 supports viral gene expression upon early infection, and that this function is dependent on the Daxx-interaction domain. Lastly, we show that knockdown of Daxx and ATRX induces reactivation of EBV from latently infected lymphoblastoid cell lines (LCLs), suggesting that Daxx and ATRX play a role in the regulation of viral chromatin. Taken together, our data demonstrate an important role of BNRF1 in supporting EBV early infection by interacting with Daxx and ATRX; and suggest that tegument disruption of PML-NB-associated antiviral resistances is a universal requirement for herpesvirus infection in the nucleus. PMID:22102817

  17. Viral FGARAT ORF75A promotes early events in lytic infection and gammaherpesvirus pathogenesis in mice

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    Hogan, Chad H.; Oldenburg, Darby G.; Kara, Mehmet

    2018-01-01

    Gammaherpesviruses encode proteins with homology to the cellular purine metabolic enzyme formyl-glycinamide-phosphoribosyl-amidotransferase (FGARAT), but the role of these viral FGARATs (vFGARATs) in the pathogenesis of a natural host has not been investigated. We report a novel role for the ORF75A vFGARAT of murine gammaherpesvirus 68 (MHV68) in infectious virion production and colonization of mice. MHV68 mutants with premature stop codons in orf75A exhibited a log reduction in acute replication in the lungs after intranasal infection, which preceded a defect in colonization of multiple host reservoirs including the mediastinal lymph nodes, peripheral blood mononuclear cells, and the spleen. Intraperitoneal infection rescued splenic latency, but not reactivation. The 75A.stop virus also exhibited defective replication in primary fibroblast and macrophage cells. Viruses produced in the absence of ORF75A were characterized by an increase in the ratio of particles to PFU. In the next round of infection this led to the alteration of early events in lytic replication including the deposition of the ORF75C tegument protein, the accelerated kinetics of viral gene expression, and induction of TNFα release and cell death. Infecting cells to deliver equivalent genomes revealed that ORF75A was required for initiating early events in infection. In contrast with the numerous phenotypes observed in the absence of ORF75A, ORF75B was dispensable for replication and pathogenesis. These studies reveal that murine rhadinovirus vFGARAT family members ORF75A and ORF75C have evolved to perform divergent functions that promote replication and colonization of the host. PMID:29390024

  18. Viral Infection in Renal Transplant Recipients

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    Jovana Cukuranovic

    2012-01-01

    Full Text Available Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens.

  19. Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques

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    Mannioui Abdelkrim

    2009-01-01

    Full Text Available Abstract Background Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied. Results The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT, with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected. Conclusion We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important

  20. Viral infections in transplant recipients.

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    Razonable, R R; Eid, A J

    2009-12-01

    Solid organ and hematopoietic stem cell transplant recipients are uniquely predisposed to develop clinical illness, often with increased severity, due to a variety of common and opportunistic viruses. Patients may acquire viral infections from the donor (donor-derived infections), from reactivation of endogenous latent virus, or from the community. Herpes viruses, most notably cytomegalovirus and Epstein Barr virus, are the most common among opportunistic viral pathogens that cause infection after solid organ and hematopoietic stem cell transplantation. The polyoma BK virus causes opportunistic clinical syndromes predominantly in kidney and allogeneic hematopoietic stem cell transplant recipients. The agents of viral hepatitis B and C present unique challenges particularly among liver transplant recipients. Respiratory viral illnesses due to influenza, respiratory syncytial virus, and parainfluenza virus may affect all types of transplant recipients, although severe clinical disease is observed more commonly among lung and allogeneic hematopoietic stem cell transplant recipients. Less common viral infections affecting transplant recipients include those caused by adenoviruses, parvovirus B19, and West Nile virus. Treatment for viruses with proven effective antiviral drug therapies should be complemented by reduction in the degree of immunosuppression. For others with no proven antiviral drugs for therapy, reduction in the degree of immunosuppression remains as the sole effective strategy for management. Prevention of viral infections is therefore of utmost importance, and this may be accomplished through vaccination, antiviral strategies, and aggressive infection control measures.

  1. Early detection of neuropathophysiology using diffusion-weighted magnetic resonance imaging in asymptomatic cats with feline immunodeficiency viral infection.

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    Bucy, Daniel S; Brown, Mark S; Bielefeldt-Ohmann, Helle; Thompson, Jesse; Bachand, Annette M; Morges, Michelle; Elder, John H; Vandewoude, Sue; Kraft, Susan L

    2011-08-01

    HIV infection results in a highly prevalent syndrome of cognitive and motor disorders designated as HIV-associated dementia (HAD). Neurologic dysfunction resembling HAD has been documented in cats infected with strain PPR of the feline immunodeficiency virus (FIV), whereas another highly pathogenic strain (C36) has not been known to cause neurologic signs. Animals experimentally infected with equivalent doses of FIV-C36 or FIV-PPR, and uninfected controls were evaluated by magnetic resonance diffusion-weighted imaging (DW-MRI) and spectroscopy (MRS) at 17.5-18 weeks post-infection, as part of a study of viral clade pathogenesis in FIV-infected cats. The goals of the MR imaging portion of the project were to determine whether this methodology was capable of detecting early neuropathophysiology in the absence of outward manifestation of neurological signs and to compare the MR imaging results for the two viral strains expected to have differing degrees of neurologic effects. We hypothesized that there would be increased diffusion, evidenced by the apparent diffusion coefficient as measured by DW-MRI, and altered metabolite ratios measured by MRS, in the brains of FIV-PPR-infected cats relative to C36-infected cats and uninfected controls. Increased apparent diffusion coefficients were seen in the white matter, gray matter, and basal ganglia of both the PPR and C36-infected (asymptomatic) cats. Thalamic MRS metabolite ratios did not differ between groups. The equivalently increased diffusion by DW-MRI suggests similar indirect neurotoxicity mechanisms for the two viral genotypes. DW-MRI is a sensitive tool to detect neuropathophysiological changes in vivo that could be useful during longitudinal studies of FIV.

  2. Older siblings, pets and early life infections: impact on gut microbiota and allergy prevalence during the first three years of life

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    Laursen, Martin Frederik; Zachariassen, Gitte; Bahl, Martin Iain

    Background: Early life infections and presence of older siblings or pets in the household are factors known to affect the risk of developing allergic diseases, and this effect is suggested to be mediated by interactions between microbes and the immune system. However, very limited research has been...... done on the effect of these factors on the developing gut microbiota in infants. Thus, we aimed to elucidate associations between older siblings, pets and early life infections, the microbial gut communities at 9 and 18 months of age and the prevalence of allergies in three year old children. Methods...... of respiratory allergy, eczema and presence of older siblings, pets and early life infections, previously collected through interviews with parents, were compared to the obtained data on bacterial taxonomy. Results: Early life infections were positively associated with the risk of developing respiratory allergy...

  3. A proteomic perspective of inbuilt viral protein regulation: pUL46 tegument protein is targeted for degradation by ICP0 during herpes simplex virus type 1 infection.

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    Lin, Aaron E; Greco, Todd M; Döhner, Katinka; Sodeik, Beate; Cristea, Ileana M

    2013-11-01

    Much like the host cells they infect, viruses must also regulate their life cycles. Herpes simples virus type 1 (HSV-1), a prominent human pathogen, uses a promoter-rich genome in conjunction with multiple viral trans-activating factors. Following entry into host cells, the virion-associated outer tegument proteins pUL46 and pUL47 act to increase expression of viral immediate-early (α) genes, thereby helping initiate the infection life cycle. Because pUL46 has gone largely unstudied, we employed a hybrid mass spectrometry-based approach to determine how pUL46 exerts its functions during early stages of infection. For a spatio-temporal characterization of pUL46, time-lapse microscopy was performed in live cells to define its dynamic localization from 2 to 24 h postinfection. Next, pUL46-containing protein complexes were immunoaffinity purified during infection of human fibroblasts and analyzed by mass spectrometry to investigate virus-virus and virus-host interactions, as well as post-translational modifications. We demonstrated that pUL46 is heavily phosphorylated in at least 23 sites. One phosphorylation site matched the consensus 14-3-3 phospho-binding motif, consistent with our identification of 14-3-3 proteins and host and viral kinases as specific pUL46 interactions. Moreover, we determined that pUL46 specifically interacts with the viral E3 ubiquitin ligase ICP0. We demonstrated that pUL46 is partially degraded in a proteasome-mediated manner during infection, and that the catalytic activity of ICP0 is responsible for this degradation. This is the first evidence of a viral protein being targeted for degradation by another viral protein during HSV-1 infection. Together, these data indicate that pUL46 levels are tightly controlled and important for the temporal regulation of viral gene expression throughout the virus life cycle. The concept of a structural virion protein, pUL46, performing nonstructural roles is likely to reflect a theme common to many viruses

  4. Early Life Arsenic Exposure and Acute and Long-term Responses to Influenza A Infection in Mice

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    Ramsey, Kathryn A.; Foong, Rachel E.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.

    2013-01-01

    Background: Arsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood. Objective: We aimed to determine if early life exposure to arsenic exacerbates the response to early life influenza infection in mice. Methods: C57BL/6 mice were exposed to arsenic in utero and throughout postnatal lif...

  5. CLINICAL EFFICACY OF IBUPROFEN IN THERAPY FOR VIRAL UPPER RESPIRATORY TRACT INFECTIONS IN INFANTS

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    I.O. Skugarevskaya

    2006-01-01

    Full Text Available A study of use of ibuprofen in cases of viral upper respiratory tract infections (Vuri in children of early childhood has proved its' safety and efficacy. This medical agent has not only terminate fever but also diminished some other symptoms of Vuri.Key words: ibuprofen, viral upper respiratory tract infections, children.

  6. A Herpesviral Immediate Early Protein Promotes Transcription Elongation of Viral Transcripts

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    Hannah L. Fox

    2017-06-01

    Full Text Available Herpes simplex virus 1 (HSV-1 genes are transcribed by cellular RNA polymerase II (RNA Pol II. While four viral immediate early proteins (ICP4, ICP0, ICP27, and ICP22 function in some capacity in viral transcription, the mechanism by which ICP22 functions remains unclear. We observed that the FACT complex (comprised of SSRP1 and Spt16 was relocalized in infected cells as a function of ICP22. ICP22 was also required for the association of FACT and the transcription elongation factors SPT5 and SPT6 with viral genomes. We further demonstrated that the FACT complex interacts with ICP22 throughout infection. We therefore hypothesized that ICP22 recruits cellular transcription elongation factors to viral genomes for efficient transcription elongation of viral genes. We reevaluated the phenotype of an ICP22 mutant virus by determining the abundance of all viral mRNAs throughout infection by transcriptome sequencing (RNA-seq. The accumulation of almost all viral mRNAs late in infection was reduced compared to the wild type, regardless of kinetic class. Using chromatin immunoprecipitation sequencing (ChIP-seq, we mapped the location of RNA Pol II on viral genes and found that RNA Pol II levels on the bodies of viral genes were reduced in the ICP22 mutant compared to wild-type virus. In contrast, the association of RNA Pol II with transcription start sites in the mutant was not reduced. Taken together, our results indicate that ICP22 plays a role in recruiting elongation factors like the FACT complex to the HSV-1 genome to allow for efficient viral transcription elongation late in viral infection and ultimately infectious virion production.

  7. Rituximab-related viral infections in lymphoma patients.

    Science.gov (United States)

    Aksoy, Sercan; Harputluoglu, Hakan; Kilickap, Saadettin; Dede, Didem Sener; Dizdar, Omer; Altundag, Kadri; Barista, Ibrahim

    2007-07-01

    Recently, a human/mouse chimeric monoclonal antibody, rituximab, has been successfully used to treat cases of B-cell non-Hodgkin's lymphoma and some autoimmune diseases. However, several viral infections related to rituximab have been reported in the literature, but were not well characterized. To further investigate this topic, relevant English language studies were identified through Medline. There were 64 previously reported cases of serious viral infection after rituximab treatment. The median age of the cases was 61 years (range: 21 - 79). The median time period from the start of rituximab treatment to viral infection diagnosis was 5.0 months (range: 1 - 20). The most frequently experienced viral infections were hepatitis B virus (HBV) (39.1%, n = 25), cytomegalovirus infection (CMV) (23.4%, n = 15), varicella-zoster virus (VZV) (9.4%, n = 6), and others (28.1%, n = 18). Of the patients with HBV infections, 13 (52.0%) died due to hepatic failure. Among the 39 cases that had viral infections other than HBV, 13 died due to these specific infections. In this study, about 50% of the rituximab-related HBV infections resulted in death, whereas this was the case in only 33% of the cases with other infections. Close monitoring for viral infection, particularly HBV and CMV, in patients treated with rituximab should be recommended.

  8. iNKT Cells and Their potential Lipid Ligands during Viral Infection

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    Anunya eOpasawatchai

    2015-07-01

    Full Text Available Invariant natural killer T (iNKT cells are a unique population of lipid reactive CD1d restricted innate-like T lymphocytes. Despite being a minor population, they serve as an early source of cytokines and promote immunological crosstalk thus bridging innate and adaptive immunity. Diseases ranging from allergy, autoimmunity, and cancer as well as infectious diseases, including viral infection, have been reported to be influenced by iNKT cells. However, it remains unclear how iNKT cells are activated during viral infection, as virus derived lipid antigens have not been reported. Cytokines may activate iNKT cells during infections from influenza and murine cytomegalovirus (MCMV, although CD1d dependent activation is evident in other viral infections. Several viruses, such as dengue virus (DENV, induce CD1d upregulation which correlates with iNKT cell activation. In contrast, Herpes simplex virus type 1 (HSV-1, Human immunodeficiency virus (HIV, Epstein-Barr virus (EBV and Human papiloma virus (HPV promote CD1d downregulation as a strategy to evade iNKT cell recognition. These observations suggest the participation of a CD1d-dependent process in the activation of iNKT cells in response to viral infection. Endogenous lipid ligands, including phospholipids as well as glycosphingolipids, such as glucosylceramide have been proposed to mediate iNKT cell activation. Pro-inflammatory signals produced during viral infection may stimulate iNKT cells through enhanced CD1d dependent endogenous lipid presentation. Furthermore, viral infection may alter lipid composition and inhibit endogenous lipid degradation. Recent advances in this field are reviewed.

  9. Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness.

    Science.gov (United States)

    Edwards, Michael R; Strong, Katherine; Cameron, Aoife; Walton, Ross P; Jackson, David J; Johnston, Sebastian L

    2017-10-01

    Viral respiratory tract infections are associated with asthma inception in early life and asthma exacerbations in older children and adults. Although how viruses influence asthma inception is poorly understood, much research has focused on the host response to respiratory viruses and how viruses can promote; or how the host response is affected by subsequent allergen sensitization and exposure. This review focuses on the innate interferon-mediated host response to respiratory viruses and discusses and summarizes the available evidence that this response is impaired or suboptimal. In addition, the ability of respiratory viruses to act in a synergistic or additive manner with T H 2 pathways will be discussed. In this review we argue that these 2 outcomes are likely linked and discuss the available evidence that shows reciprocal negative regulation between innate interferons and T H 2 mediators. With the renewed interest in anti-T H 2 biologics, we propose a rationale for why they are particularly successful in controlling asthma exacerbations and suggest ways in which future clinical studies could be used to find direct evidence for this hypothesis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. A Herpesviral Immediate Early Protein Promotes Transcription Elongation of Viral Transcripts.

    Science.gov (United States)

    Fox, Hannah L; Dembowski, Jill A; DeLuca, Neal A

    2017-06-13

    Herpes simplex virus 1 (HSV-1) genes are transcribed by cellular RNA polymerase II (RNA Pol II). While four viral immediate early proteins (ICP4, ICP0, ICP27, and ICP22) function in some capacity in viral transcription, the mechanism by which ICP22 functions remains unclear. We observed that the FACT complex (comprised of SSRP1 and Spt16) was relocalized in infected cells as a function of ICP22. ICP22 was also required for the association of FACT and the transcription elongation factors SPT5 and SPT6 with viral genomes. We further demonstrated that the FACT complex interacts with ICP22 throughout infection. We therefore hypothesized that ICP22 recruits cellular transcription elongation factors to viral genomes for efficient transcription elongation of viral genes. We reevaluated the phenotype of an ICP22 mutant virus by determining the abundance of all viral mRNAs throughout infection by transcriptome sequencing (RNA-seq). The accumulation of almost all viral mRNAs late in infection was reduced compared to the wild type, regardless of kinetic class. Using chromatin immunoprecipitation sequencing (ChIP-seq), we mapped the location of RNA Pol II on viral genes and found that RNA Pol II levels on the bodies of viral genes were reduced in the ICP22 mutant compared to wild-type virus. In contrast, the association of RNA Pol II with transcription start sites in the mutant was not reduced. Taken together, our results indicate that ICP22 plays a role in recruiting elongation factors like the FACT complex to the HSV-1 genome to allow for efficient viral transcription elongation late in viral infection and ultimately infectious virion production. IMPORTANCE HSV-1 interacts with many cellular proteins throughout productive infection. Here, we demonstrate the interaction of a viral protein, ICP22, with a subset of cellular proteins known to be involved in transcription elongation. We determined that ICP22 is required to recruit the FACT complex and other transcription

  11. DEFEAT OF THE CARDIOVASCULAR SYSTEM IN VIRAL INFECTIONS

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    E. V. Sharipova

    2017-01-01

    Full Text Available Article is devoted to studying of the submitted epidemiological, clinical, tool, laboratory data on pathology of cardiovascular system at various viral infections. The review is based on results of domestic and foreign researches. At viral infections damage of heart and his carrying-out system perhaps as during the sharp period of a disease, and the period of a convalescence or at the chronic course of virus process. The greatest cardiothrogenism is possessed by enteroviruses, which affect the myocardium in 5–15% of cases. Much attention is paid to herpesviruses, widespread, persistently persistent in the body, as one of the reasons for the development of dilated cardiomyopathy, coronary vasculitis, early atherosclerosis, cardiac rhythm disturbance. Other infections that may affect the cardiovascular system include influenza viruses, adenovirus, poliovirus, Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, hepatitis, mumps, rubella, herpes simplex, varicella, arbovirus, respiratory-syntial virus, yellow fever virus et al. Complications from cardiovascular system can come to light at various age.

  12. Frequency of viral etiology in symptomatic adult upper respiratory tract infections

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    Raquel Cirlene da Silva

    2015-01-01

    Conclusion: Results presented in this report suggest that respiratory viral infections are largely under diagnosed in immunocompetent adults. Although the majority of young adult infections are not life-threatening they may impose a significant burden, especially in developing countries since these individuals represent a large fraction of the working force.

  13. The impact of early immune destruction on the kinetics of postacute viral replication in rhesus monkey infected with the simian-human immunodeficiency virus 89.6P

    International Nuclear Information System (INIS)

    Zhang Zhiqiang; Schleif, William A.; Casimiro, Danilo R.; Handt, Larry; Chen, Minchun; Davies, Mary-Ellen; Liang Xiaoping; Fu Tongming; Tang Aimin; Wilson, Keith A.; McElhaugh, Michael; Carella, Anthony; Tan, Charles; Connolly, Brett; Hill, Susan; Klein, Hilton; Emini, Emilio A.; Shiver, John W.

    2004-01-01

    Set-point viral load is positively correlated with the extent of initial viral replication in pathogenic simian-human immunodeficiency virus (SHIV) infection. To elucidate the mechanisms underlying the correlation, we conducted a systematic investigation in rhesus monkeys infected with the highly pathogenic SHIV 89.6P. This model is widely used in the preclinical evaluation of AIDS vaccine candidates and a thorough understanding of the model's biology is important to the proper interpretation of these evaluations. We found that the levels of peak viremia were positively correlated not only with the levels of set-point viremia but, importantly, with the extent of initial overall immune destruction as indicated by the degree of CD4 + T cell depletion and lymph node germinal center (GC) formation. The extent of initial overall immune destruction was inversely correlated with subsequent development and maintenance of virus-specific cellular and humoral immune responses. Thus, these data suggest that the extent of early immune damage determines the development and durability of virus-specific immunity, thereby playing a critical role in establishing the levels of set-point viral replication in SHIV infection. Vaccines that limit both the initial viral replication and the extent of early immune damage will therefore mediate long-term virus replication control and mitigation of long-term immune destruction in this model of immunodeficiency virus infection

  14. Hematological and biochemical indicators for the early diagnosis of dengue viral infection

    International Nuclear Information System (INIS)

    Butt, N.; Abbasi, A.; Sheikh, Q.H.

    2008-01-01

    To determine the haematological and biochemical indicators for the early diagnosis of dengue viral infection. Patients presenting with a fever of less than 2 weeks duration, generalized morbiliform rash and bleeding manifestations were included. Clinical history was recorded and patients were placed on fluid and haematological support. Diagnosis was established by Polymerase Chain Reaction (PCR) for dengue virus or detection of dengue virus specific IgM and IgG. One hundred and four patients met the inclusion criteria during the study period. Sixty six patients had clinical and haematological features suggestive of grade I Dengue Hemorrhagic Fever (DHF); 34 patients had grade II DHF and 4 had grade III DHF out of whom 3 progressed to grade IV DHF. All the patients presented with fever followed by generalized morbiliform rash (81.73%), vomiting (79.8%), abdominal pain (65.38%), backache (62.5%), depression (60.6%) and mucosal bleeding manifestations (34.6%). Clinically, conjunctival infection was present in 93 patients (89.4%), hepatomegaly 59 (56.7%), lymphadenopathy in 17 (16.3%), splenomegaly in 13 (12.5%), pleural effusion in 11 (10.5%) and ascites in 8 (7.6%). Common laboratory findings were thrombocytopenia in 100% patients, leucopenia in 55 (52.8%), raised hematocrit in 52 (50%), and elevated aminotransferases, gamma GT in 100 (96%) patients. The overall mortality was 2.88%. In this series clinical history and examination supported by the triad of thrombocytopenia, raised hematocrit and elevated liver enzymes was sufficient for the early diagnosis of dengue hemorrhagic fever without waiting for dengue serology. (author)

  15. Oxygen tension level and human viral infections

    Energy Technology Data Exchange (ETDEWEB)

    Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr [Centre des Innovations Thérapeutiques en Oncologie et Hématologie (CITOH), CHU Saint-Louis, Paris (France); Université Denis Diderot, Sorbonne Paris Cité Paris, Paris (France); Casetti, Luana [Institut Cochin INSERM U1016, Paris (France); François, Jean-Hugues; Capron, Claude [Institut Cochin INSERM U1016, Paris (France); Laboratoire d' Hématologie, Hôpital Ambroise Paré, Boulogne (France); Université de Versailles Saint-Quentin en Yvelynes, Versailles (France); Pillet, Sylvie [Laboratoire de Bactériologie-Virologie-Hygiène, CHU de Saint-Etienne, Saint-Etienne (France); Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon (France)

    2013-09-15

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.

  16. Retrospective Analysis of Bacterial and Viral Co-Infections in Pneumocystis spp. Positive Lung Samples of Austrian Pigs with Pneumonia.

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    Christiane Weissenbacher-Lang

    Full Text Available Aim of this study was the retrospective investigation of viral (porcine circovirus type 2 (PCV2, porcine reproductive and respiratory syndrome virus (PRRSV, torque teno sus virus type 1 and 2 (TTSuV1, TTSuV2 and bacterial (Bordetella bronchiseptica (B. b., Mycoplasma hyopneumoniae (M. h., and Pasteurella multocida (P. m. co-infections in 110 Pneumocystis spp. positive lung samples of Austrian pigs with pneumonia. Fifty-one % were positive for PCV2, 7% for PRRSV, 22% for TTSuV1, 48% for TTSuV2, 6% for B. b., 29% for M. h., and 21% for P. m. In 38.2% only viral, in 3.6% only bacterial and in 40.0% both, viral and bacterial pathogens were detected. In 29.1% of the cases a co-infection with 1 pathogen, in 28.2% with 2, in 17.3% with 3, and in 7.3% with 4 different infectious agents were observed. The exposure to Pneumocystis significantly decreased the risk of a co-infection with PRRSV in weaning piglets; all other odds ratios were not significant. Four categories of results were compared: I = P. spp. + only viral co-infectants, II = P. spp. + both viral and bacterial co-infectants, III = P. spp. + only bacterial co-infectants, and IV = P. spp. single infection. The evaluation of all samples and the age class of the weaning piglets resulted in a predomination of the categories I and II. In contrast, the suckling piglets showed more samples of category I and IV. In the group of fattening pigs, category II predominated. Suckling piglets can be infected with P. spp. early in life. With increasing age this single infections can be complicated by co-infections with other respiratory diseases.

  17. Symptomatic and asymptomatic respiratory viral infections in the first year of life: association with acute otitis media development.

    Science.gov (United States)

    Chonmaitree, Tasnee; Alvarez-Fernandez, Pedro; Jennings, Kristofer; Trujillo, Rocio; Marom, Tal; Loeffelholz, Michael J; Miller, Aaron L; McCormick, David P; Patel, Janak A; Pyles, Richard B

    2015-01-01

    Sensitive diagnostic assays have increased the detection of viruses in asymptomatic individuals. The clinical significance of asymptomatic respiratory viral infection in infants is unknown. High-throughput, quantitative polymerase chain reaction assays were used to detect 13 common respiratory viruses from nasopharyngeal specimens collected during 2028 visits from 362 infants followed from near birth up to 12 months of age. Specimens were collected at monthly interval (months 1-6 and month 9) and during upper respiratory tract infection (URTI) episodes. Subjects were followed closely for acute otitis media (AOM) development. Viruses were detected in 76% of 394 URTI specimens and 27% of asymptomatic monthly specimens. Rhinovirus was detected most often; multiple viruses were detected in 29% of the specimens. Generalized mixed-model analyses associated symptoms with increasing age and female sex; detection of respiratory syncytial virus (RSV), influenza, rhinovirus, metapneumovirus, and adenovirus was highly associated with symptoms. Increasing age was also associated with multiple virus detection. Overall, 403 asymptomatic viral infections in 237 infants were identified. Viral load was significantly higher in URTI specimens than asymptomatic specimens but did not differentiate cases of URTI with and without AOM complication. The rate of AOM complicating URTI was 27%; no AOM occurred following asymptomatic viral infections. AOM development was associated with increasing age and infection with RSV, rhinovirus, enterovirus, adenovirus, and bocavirus. Compared to symptomatic infection, asymptomatic viral infection in infants is associated with young age, male sex, low viral load, specific viruses, and single virus detection. Asymptomatic viral infection did not result in AOM. © 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.

  18. Expression kinetics of key genes in the early innate immune response to Great Lakes viral hemorrhagic septicemia virus IVb infection in yellow perch (Perca flavescens)

    Science.gov (United States)

    Olson, Wendy; Emmenegger, Eveline; Glenn, Jolene; Simchick, Crystal; Winton, Jim; Goetz, Frederick

    2013-01-01

    The recently discovered strain of viral hemorrhagic septicemia virus, VHSV-IVb, represents an example of the introduction of an extremely pathogenic rhabdovirus capable of infecting a wide variety of new fish species in a new host-environment. The goal of the present study was to delineate the expression kinetics of key genes in the innate immune response relative to the very early stages of VHSV-IVb infection using the yellow perch (Perca flavescens) as a model. Administration of VHSV-IVb by IP-injection into juvenile yellow perch resulted in 84% cumulative mortality, indicating their high susceptibility to this disease. In fish sampled in the very early stages of infection, a significant up-regulation of Mx gene expression in the liver, as well as IL-1β and SAA activation in the head kidney, spleen, and liver was directly correlated to viral load. The potential down-regulation of Mx in the hematopoietic tissues, head kidney and spleen, may represent a strategy utilized by the virus to increase replication.

  19. Schrödinger's Cheshire Cat: Are Haploid Emiliania huxleyi Cells Resistant to Viral Infection or Not?

    Science.gov (United States)

    Mordecai, Gideon J; Verret, Frederic; Highfield, Andrea; Schroeder, Declan C

    2017-03-18

    Emiliania huxleyi is the main calcite producer on Earth and is routinely infected by a virus (EhV); a double stranded DNA (dsDNA) virus belonging to the family Phycodnaviridae . E. huxleyi exhibits a haplodiploid life cycle; the calcified diploid stage is non-motile and forms extensive blooms. The haploid phase is a non-calcified biflagellated cell bearing organic scales. Haploid cells are thought to resist infection, through a process deemed the "Cheshire Cat" escape strategy; however, a recent study detected the presence of viral lipids in the same haploid strain. Here we report on the application of an E. huxleyi CCMP1516 EhV-86 combined tiling array (TA) that further confirms an EhV infection in the RCC1217 haploid strain, which grew without any signs of cell lysis. Reverse transcription polymerase chain reaction (RT-PCR) and PCR verified the presence of viral RNA in the haploid cells, yet indicated an absence of viral DNA, respectively. These infected cells are an alternative stage of the virus life cycle deemed the haplococcolithovirocell. In this instance, the host is both resistant to and infected by EhV, i.e., the viral transcriptome is present in haploid cells whilst there is no evidence of viral lysis. This superimposed state is reminiscent of Schrödinger's cat; of being simultaneously both dead and alive.

  20. PAR-1 contributes to the innate immune response during viral infection

    Science.gov (United States)

    Antoniak, Silvio; Owens, A. Phillip; Baunacke, Martin; Williams, Julie C.; Lee, Rebecca D.; Weithäuser, Alice; Sheridan, Patricia A.; Malz, Ronny; Luyendyk, James P.; Esserman, Denise A.; Trejo, JoAnn; Kirchhofer, Daniel; Blaxall, Burns C.; Pawlinski, Rafal; Beck, Melinda A.; Rauch, Ursula; Mackman, Nigel

    2013-01-01

    Coagulation is a host defense system that limits the spread of pathogens. Coagulation proteases, such as thrombin, also activate cells by cleaving PARs. In this study, we analyzed the role of PAR-1 in coxsackievirus B3–induced (CVB3-induced) myocarditis and influenza A infection. CVB3-infected Par1–/– mice expressed reduced levels of IFN-β and CXCL10 during the early phase of infection compared with Par1+/+ mice that resulted in higher viral loads and cardiac injury at day 8 after infection. Inhibition of either tissue factor or thrombin in WT mice also significantly increased CVB3 levels in the heart and cardiac injury compared with controls. BM transplantation experiments demonstrated that PAR-1 in nonhematopoietic cells protected mice from CVB3 infection. Transgenic mice overexpressing PAR-1 in cardiomyocytes had reduced CVB3-induced myocarditis. We found that cooperative signaling between PAR-1 and TLR3 in mouse cardiac fibroblasts enhanced activation of p38 and induction of IFN-β and CXCL10 expression. Par1–/– mice also had decreased CXCL10 expression and increased viral levels in the lung after influenza A infection compared with Par1+/+ mice. Our results indicate that the tissue factor/thrombin/PAR-1 pathway enhances IFN-β expression and contributes to the innate immune response during single-stranded RNA viral infection. PMID:23391721

  1. A new cell culture model to genetically dissect the complete human papillomavirus life cycle.

    Science.gov (United States)

    Bienkowska-Haba, Malgorzata; Luszczek, Wioleta; Myers, Julia E; Keiffer, Timothy R; DiGiuseppe, Stephen; Polk, Paula; Bodily, Jason M; Scott, Rona S; Sapp, Martin

    2018-03-01

    Herein, we describe a novel infection model that achieves highly efficient infection of primary keratinocytes with human papillomavirus type 16 (HPV16). This cell culture model does not depend on immortalization and is amenable to extensive genetic analyses. In monolayer cell culture, the early but not late promoter was active and yielded a spliced viral transcript pattern similar to HPV16-immortalized keratinocytes. However, relative levels of the E8^E2 transcript increased over time post infection suggesting the expression of this viral repressor is regulated independently of other early proteins and that it may be important for the shift from the establishment to the maintenance phase of the viral life cycle. Both the early and the late promoter were strongly activated when infected cells were subjected to differentiation by growth in methylcellulose. When grown as organotypic raft cultures, HPV16-infected cells expressed late E1^E4 and L1 proteins and replication foci were detected, suggesting that they supported the completion of the viral life cycle. As a proof of principle that the infection system may be used for genetic dissection of viral factors, we analyzed E1, E6 and E7 translation termination linker mutant virus for establishment of infection and genome maintenance. E1 but not E6 and E7 was essential to establish infection. Furthermore, E6 but not E7 was required for episomal genome maintenance. Primary keratinocytes infected with wild type HPV16 immortalized, whereas keratinocytes infected with E6 and E7 knockout virus began to senesce 25 to 35 days post infection. The novel infection model provides a powerful genetic tool to study the role of viral proteins throughout the viral life cycle but especially for immediate early events and enables us to compare low- and high-risk HPV types in the context of infection.

  2. A new cell culture model to genetically dissect the complete human papillomavirus life cycle.

    Directory of Open Access Journals (Sweden)

    Malgorzata Bienkowska-Haba

    2018-03-01

    Full Text Available Herein, we describe a novel infection model that achieves highly efficient infection of primary keratinocytes with human papillomavirus type 16 (HPV16. This cell culture model does not depend on immortalization and is amenable to extensive genetic analyses. In monolayer cell culture, the early but not late promoter was active and yielded a spliced viral transcript pattern similar to HPV16-immortalized keratinocytes. However, relative levels of the E8^E2 transcript increased over time post infection suggesting the expression of this viral repressor is regulated independently of other early proteins and that it may be important for the shift from the establishment to the maintenance phase of the viral life cycle. Both the early and the late promoter were strongly activated when infected cells were subjected to differentiation by growth in methylcellulose. When grown as organotypic raft cultures, HPV16-infected cells expressed late E1^E4 and L1 proteins and replication foci were detected, suggesting that they supported the completion of the viral life cycle. As a proof of principle that the infection system may be used for genetic dissection of viral factors, we analyzed E1, E6 and E7 translation termination linker mutant virus for establishment of infection and genome maintenance. E1 but not E6 and E7 was essential to establish infection. Furthermore, E6 but not E7 was required for episomal genome maintenance. Primary keratinocytes infected with wild type HPV16 immortalized, whereas keratinocytes infected with E6 and E7 knockout virus began to senesce 25 to 35 days post infection. The novel infection model provides a powerful genetic tool to study the role of viral proteins throughout the viral life cycle but especially for immediate early events and enables us to compare low- and high-risk HPV types in the context of infection.

  3. Acute Viral Respiratory Infection Rapidly Induces a CD8+ T Cell Exhaustion-like Phenotype.

    Science.gov (United States)

    Erickson, John J; Lu, Pengcheng; Wen, Sherry; Hastings, Andrew K; Gilchuk, Pavlo; Joyce, Sebastian; Shyr, Yu; Williams, John V

    2015-11-01

    Acute viral infections typically generate functional effector CD8(+) T cells (TCD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung TCD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to TCD8 impairment during viral lower respiratory infection, but how it regulates TCD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung TCD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung TCD8 to functional spleen TCD8 in the same human metapneumovirus-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung TCD8. We then compared the gene expression of TCD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung TCD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for TCD8 impairment or inhibitory receptor upregulation, but that viral Ag-induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung TCD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors. Copyright © 2015 by The American Association of Immunologists, Inc.

  4. Viral infections as controlling factors for the deep biosphere? (Invited)

    Science.gov (United States)

    Engelen, B.; Engelhardt, T.; Sahlberg, M.; Cypionka, H.

    2009-12-01

    The marine deep biosphere represents the largest biotope on Earth. Throughout the last years, we have obtained interesting insights into its microbial community composition. However, one component that was completely overlooked so far is the viral inventory of deep-subsurface sediments. While viral infections were identified to have a major impact on the benthic microflora of deep-sea surface sediments (Danavaro et al. 2008), no studies were performed on deep-biosphere samples, so far. As grazers probably play only a minor role in anoxic and highly compressed deep sediments, viruses might be the main “predators” for indigenous microorganisms. Furthermore, the release of cell components, called “the viral shunt”, could have a major impact on the deep biosphere in providing labile organic compounds to non-infected microorganisms in these generally nutrient depleted sediments. However, direct counting of viruses in sediments is highly challenging due to the small size of viruses and the high background of small particles. Even molecular surveys using “universal” PCR primers that target phage-specific genes fail due to the vast phage diversity. One solution for this problem is the lysogenic viral life cycle as many bacteriophages integrate their DNA into the host genome. It is estimated that up to 70% of cultivated bacteria contain prophages within their genome. Therefore, culture collections (Batzke et al. 2007) represent an archive of the viral composition within the respective habitat. These prophages can be induced to become free phage particles in stimulation experiments in which the host cells are set under certain stress situations such as a treatment with UV exposure or DNA-damaging antibiotics. The study of the viral component within the deep biosphere offers to answer the following questions: To which extent are deep-biosphere populations controlled by viral infections? What is the inter- and intra-specific diversity and the host-specific viral

  5. Association between infection early in life and mental disorders among youth in the community: a cross-sectional study

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    Goodwin Renee D

    2011-11-01

    Full Text Available Abstract Background The objective of this study was to examine the association between infection early in life and mental disorders among youth in the community. Methods Data were drawn from the MECA (Methods in Epidemiology of Child and Adolescent psychopathology, a community-based study of 1,285 youth in the United States conducted in 1992. Multiple logistic regression analyses were used to investigate the association between parent/caregiver-reported infection early in life and DSM/DISC diagnoses of mental disorders at ages 9-17. Results Infection early in life was associated with a significantly increased odds of major depression (OR = 3.9, social phobia (OR = 5.8, overanxious disorder (OR = 6.1, panic disorder (OR = 12.1, and oppositional defiant disorder (OR = 3.7. Conclusions These findings are consistent with and extend previous results by providing new evidence suggesting a link between infection early in life and increased risk of depression and anxiety disorders among youth. These results should be considered preliminary. Replication of these findings with longitudinal epidemiologic data is needed. Possible mechanisms are discussed.

  6. Prior Puma Lentivirus Infection Modifies Early Immune Responses and Attenuates Feline Immunodeficiency Virus Infection in Cats

    Directory of Open Access Journals (Sweden)

    Wendy S. Sprague

    2018-04-01

    Full Text Available We previously showed that cats that were infected with non-pathogenic Puma lentivirus (PLV and then infected with pathogenic feline immunodeficiency virus (FIV (co-infection with the host adapted/pathogenic virus had delayed FIV proviral and RNA viral loads in blood, with viral set-points that were lower than cats infected solely with FIV. This difference was associated with global CD4+ T cell preservation, greater interferon gamma (IFN-γ mRNA expression, and no cytotoxic T lymphocyte responses in co-infected cats relative to cats with a single FIV infection. In this study, we reinforced previous observations that prior exposure to an apathogenic lentivirus infection can diminish the effects of acute infection with a second, more virulent, viral exposure. In addition, we investigated whether the viral load differences that were observed between PLV/FIV and FIV infected cats were associated with different immunocyte phenotypes and cytokines. We found that the immune landscape at the time of FIV infection influences the infection outcome. The novel findings in this study advance our knowledge about early immune correlates and documents an immune state that is associated with PLV/FIV co-infection that has positive outcomes for lentiviral diseases.

  7. Hepatitis A viral load in relation to severity of the infection.

    Science.gov (United States)

    Fujiwara, Keiichi; Kojima, Hiroshige; Yasui, Shin; Okitsu, Koichiro; Yonemitsu, Yutaka; Omata, Masao; Yokosuka, Osamu

    2011-02-01

    A correlation between hepatitis A virus (HAV) genomes and the clinical severity of hepatitis A has not been established. The viral load in sera of hepatitis A patients was examined to determine the possible association between hepatitis A severity and HAV replication. One hundred sixty-four serum samples from 91 Japanese patients with sporadic hepatitis A, comprising 11 patients with fulminant hepatitis, 10 with severe acute hepatitis, and 70 with self-limited acute hepatitis, were tested for HAV RNA. The sera included 83 serial samples from 20 patients. Viral load was measured by real-time RT-PCR. The detection rates of HAV RNA from fulminant, severe acute, and acute hepatitis were 10/11 (91%), 10/10 (100%), and 55/70 (79%), respectively. Mean values of HAV RNA at admission were 3.48 ± 1.30 logcopies/ml in fulminant, 4.19 ± 1.03 in severe acute, and 2.65 ± 1.64 in acute hepatitis. Patients with severe infection such as fulminant hepatitis and severe acute hepatitis had higher initial viral load than patients with less severe infection (P hepatitis after clinical onset (P = 0.19). HAV RNA was detectable quantitatively in the majority of the sera of hepatitis A cases during the early convalescent phase by real-time PCR. Higher initial viral replication was found in severely infected patients. An excessive host immune response might follow, reducing the viral load rapidly as a result of the destruction of large numbers of HAV-infected hepatocytes, and in turn severe disease might be induced. 2010 Wiley-Liss, Inc.

  8. T cells for viral infections after allogeneic hematopoietic stem cell transplant.

    Science.gov (United States)

    Bollard, Catherine M; Heslop, Helen E

    2016-06-30

    Despite recent advances in the field of allogeneic hematopoietic stem cell transplantation (HSCT), viral infections are still a major complication during the period of immune suppression that follows the procedure. Adoptive transfer of donor-derived virus-specific cytotoxic T cells (VSTs) is a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after HSCT. Early proof of principle studies demonstrated that the administration of donor-derived T cells specific for cytomegalovirus or Epstein-Barr virus (EBV) could effectively restore virus-specific immunity and control viral infections. Subsequent studies using different expansion or direct selection techniques have shown that donor-derived VSTs confer protection in vivo after adoptive transfer in 70% to 90% of recipients. Because a major cause of failure is lack of immunity to the infecting virus in a naïve donor, more recent studies have infused closely matched third-party VSTs and reported response rates of 60% to 70%. Current efforts have focused on broadening the applicability of this approach by: (1) extending the number of viral antigens being targeted, (2) simplifying manufacture, (3) exploring strategies for recipients of virus-naïve donor grafts, and (4) developing and optimizing "off the shelf" approaches. © 2016 by The American Society of Hematology.

  9. Mast cells in viral infections

    Directory of Open Access Journals (Sweden)

    Piotr Witczak

    2012-04-01

    Full Text Available  There are some premises suggesting that mast cells are involved in the mechanisms of anti-virus defense and in viral disease pathomechanisms. Mast cells are particularly numerous at the portals of infections and thus may have immediate and easy contact with the external environment and invading pathogens. These cells express receptors responsible for recognition of virus-derived PAMP molecules, mainly Toll-like receptors (TLR3, TLR7/8 and TLR9, but also RIG-I-like and NOD-like molecules. Furthermore, mast cells generate various mediators, cytokines and chemokines which modulate the intensity of inflammation and regulate the course of innate and adaptive anti-viral immunity. Indirect evidence for the role of mast cells in viral infections is also provided by clinical observations and results of animal studies. Currently, more and more data indicate that mast cells can be infected by some viruses (dengue virus, adenoviruses, hantaviruses, cytomegaloviruses, reoviruses, HIV-1 virus. It is also demonstrated that mast cells can release pre formed mediators as well as synthesize de novo eicosanoids in response to stimulation by viruses. Several data indicate that virus-stimulated mast cells secrete cytokines and chemokines, including interferons as well as chemokines with a key role in NK and Tc lymphocyte influx. Moreover, some information indicates that mast cell stimulation via TLR3, TLR7/8 and TLR9 can affect their adhesion to extracellular matrix proteins and chemotaxis, and influence expression of some membrane molecules. Critical analysis of current data leads to the conclusion that it is not yet possible to make definitive statements about the role of mast cells in innate and acquired defense mechanisms developing in the course of viral infection and/or pathomechanisms of viral diseases.

  10. Schrödinger’s Cheshire Cat: Are Haploid Emiliania huxleyi Cells Resistant to Viral Infection or Not?

    Directory of Open Access Journals (Sweden)

    Gideon J. Mordecai

    2017-03-01

    Full Text Available Emiliania huxleyi is the main calcite producer on Earth and is routinely infected by a virus (EhV; a double stranded DNA (dsDNA virus belonging to the family Phycodnaviridae. E. huxleyi exhibits a haplodiploid life cycle; the calcified diploid stage is non-motile and forms extensive blooms. The haploid phase is a non-calcified biflagellated cell bearing organic scales. Haploid cells are thought to resist infection, through a process deemed the “Cheshire Cat” escape strategy; however, a recent study detected the presence of viral lipids in the same haploid strain. Here we report on the application of an E. huxleyi CCMP1516 EhV-86 combined tiling array (TA that further confirms an EhV infection in the RCC1217 haploid strain, which grew without any signs of cell lysis. Reverse transcription polymerase chain reaction (RT-PCR and PCR verified the presence of viral RNA in the haploid cells, yet indicated an absence of viral DNA, respectively. These infected cells are an alternative stage of the virus life cycle deemed the haplococcolithovirocell. In this instance, the host is both resistant to and infected by EhV, i.e., the viral transcriptome is present in haploid cells whilst there is no evidence of viral lysis. This superimposed state is reminiscent of Schrödinger’s cat; of being simultaneously both dead and alive.

  11. Schrödinger’s Cheshire Cat: Are Haploid Emiliania huxleyi Cells Resistant to Viral Infection or Not?

    Science.gov (United States)

    Mordecai, Gideon J.; Verret, Frederic; Highfield, Andrea; Schroeder, Declan C.

    2017-01-01

    Emiliania huxleyi is the main calcite producer on Earth and is routinely infected by a virus (EhV); a double stranded DNA (dsDNA) virus belonging to the family Phycodnaviridae. E. huxleyi exhibits a haplodiploid life cycle; the calcified diploid stage is non-motile and forms extensive blooms. The haploid phase is a non-calcified biflagellated cell bearing organic scales. Haploid cells are thought to resist infection, through a process deemed the “Cheshire Cat” escape strategy; however, a recent study detected the presence of viral lipids in the same haploid strain. Here we report on the application of an E. huxleyi CCMP1516 EhV-86 combined tiling array (TA) that further confirms an EhV infection in the RCC1217 haploid strain, which grew without any signs of cell lysis. Reverse transcription polymerase chain reaction (RT-PCR) and PCR verified the presence of viral RNA in the haploid cells, yet indicated an absence of viral DNA, respectively. These infected cells are an alternative stage of the virus life cycle deemed the haplococcolithovirocell. In this instance, the host is both resistant to and infected by EhV, i.e., the viral transcriptome is present in haploid cells whilst there is no evidence of viral lysis. This superimposed state is reminiscent of Schrödinger’s cat; of being simultaneously both dead and alive. PMID:28335465

  12. Early syphilis affects markers of HIV infection.

    Science.gov (United States)

    Kotsafti, Ourania; Paparizos, Vassilios; Kourkounti, Sofia; Chatziioannou, Argiro; Nicolaidou, Electra; Kapsimali, Violetta; Antoniou, Christina

    2016-08-01

    The objective of this study was to investigate if early syphilis infection affects markers of HIV infection; CD4 T cells and viral load (VL). A retrospective study was performed on 160 HIV-positive patients (111 receiving antiretroviral therapy [ART] and 49 without ART). Early syphilis diagnosis was made in HIV patients during their follow-up at the HIV/AIDS Unit at a Greek Dermatology and Venereology Unit. The patients' blood tests were available at the time of diagnosis, as well as before and 12 weeks after early syphilis diagnosis. CD4 T cell counts and VL levels were measured. It was found that syphilis infection had a negative impact on the CD4 T cell counts in both groups, with reduced CD4 T cell counts observed in 84.6% (99/111) and 79.5% (39/49) of patients receiving and not receiving ART, respectively. After treatment for syphilis, CD4 T cell counts returned to pre-treatment levels in most patients, especially those receiving ART. There was a slight and transient VL increase. Patients receiving ART had a 27% increase in VL, compared to 71.4% among patients not receiving ART. Although the VL increase was slight (41-14,000 copies/ml) in the group under treatment, 4-5% (5/111) patients did not return to pre-treatment levels. Moreover, viral mutations associated with treatment resistance were identified in these patients. Early syphilis accelerates and complicates the progression of HIV infection. Early diagnosis and treatment of syphilis may prevent infection-associated complications in most instances. Consequently, prevention of syphilis and other sexually transmitted infections is of great importance for patients infected with HIV. © The Author(s) 2016.

  13. c-Myc Represses Transcription of Epstein-Barr Virus Latent Membrane Protein 1 Early after Primary B Cell Infection.

    Science.gov (United States)

    Price, Alexander M; Messinger, Joshua E; Luftig, Micah A

    2018-01-15

    Recent evidence has shown that the Epstein-Barr virus (EBV) oncogene LMP1 is not expressed at high levels early after EBV infection of primary B cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (LCLs). In this study, we found that expression of LMP1 increased 50-fold between 7 days postinfection and the LCL state. Metabolic labeling of nascent transcribed mRNA indicated that this was primarily a transcription-mediated event. EBNA2, the key viral transcription factor regulating LMP1, and CTCF, an important chromatin insulator, were recruited to the LMP1 locus similarly early and late after infection. However, the activating histone H3K9Ac mark was enriched at the LMP1 promoter in LCLs relative to that in infected B cells early after infection. We found that high c-Myc activity in EBV-infected lymphoma cells as well as overexpression of c-Myc in an LCL model system repressed LMP1 transcription. Finally, we found that chemical inhibition of c-Myc both in LCLs and early after primary B cell infection increased LMP1 expression. These data support a model in which high levels of endogenous c-Myc activity induced early after primary B cell infection directly repress LMP1 transcription. IMPORTANCE EBV is a highly successful pathogen that latently infects more than 90% of adults worldwide and is also causally associated with a number of B cell malignancies. During the latent life cycle, EBV expresses a set of viral oncoproteins and noncoding RNAs with the potential to promote cancer. Critical among these is the viral latent membrane protein LMP1. Prior work suggests that LMP1 is essential for EBV to immortalize B cells, but our recent work indicates that LMP1 is not produced at high levels during the first few weeks after infection. Here we show that transcription of the LMP1 gene can be negatively regulated by a host transcription factor, c-Myc. Ultimately, understanding the regulation of EBV oncogenes will allow us

  14. Dried blood spots, valid screening for viral hepatitis and human immunodeficiency virus in real-life

    DEFF Research Database (Denmark)

    Mössner, Belinda K; Staugaard, Benjamin; Jensen, Janne

    2016-01-01

    AIM: To detect chronic hepatitis B (CHB), chronic hepatitis C (CHC) and human immunodeficiency virus (HIV) infections in dried blood spot (DBS) and compare these samples to venous blood sampling in real-life. METHODS: We included prospective patients with known viral infections from drug treatment......, but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS (68% and 42%). CONCLUSION: DBS sampling, combined with an automated analysis system, is a feasible screening method to diagnose chronic viral hepatitis and HIV...

  15. Herpesviral ICP0 Protein Promotes Two Waves of Heterochromatin Removal on an Early Viral Promoter during Lytic Infection

    Directory of Open Access Journals (Sweden)

    Jennifer S. Lee

    2016-01-01

    Full Text Available Herpesviruses must contend with host cell epigenetic silencing responses acting on their genomes upon entry into the host cell nucleus. In this study, we confirmed that unchromatinized herpes simplex virus 1 (HSV-1 genomes enter primary human foreskin fibroblasts and are rapidly subjected to assembly of nucleosomes and association with repressive heterochromatin modifications such as histone 3 (H3 lysine 9-trimethylation (H3K9me3 and lysine 27-trimethylation (H3K27me3 during the first 1 to 2 h postinfection. Kinetic analysis of the modulation of nucleosomes and heterochromatin modifications over the course of lytic infection demonstrates a progressive removal that coincided with initiation of viral gene expression. We obtained evidence for three phases of heterochromatin removal from an early gene promoter: an initial removal of histones and heterochromatin not dependent on ICP0, a second ICP0-dependent round of removal of H3K9me3 that is independent of viral DNA synthesis, and a third phase of H3K27me3 removal that is dependent on ICP0 and viral DNA synthesis. The presence of ICP0 in transfected cells is also sufficient to promote removal of histones and H3K9me3 modifications of cotransfected genes. Overall, these results show that ICP0 promotes histone removal, a reduction of H3K9me3 modifications, and a later indirect reduction of H3K27me3 modifications following viral early gene expression and DNA synthesis. Therefore, HSV ICP0 promotes the reversal of host epigenetic silencing mechanisms by several mechanisms.

  16. Nasopharyngeal polymicrobial colonization during health, viral upper respiratory infection and upper respiratory bacterial infection.

    Science.gov (United States)

    Xu, Qingfu; Wischmeyer, Jareth; Gonzalez, Eduardo; Pichichero, Michael E

    2017-07-01

    We sought to understand how polymicrobial colonization varies during health, viral upper respiratory infection (URI) and acute upper respiratory bacterial infection to understand differences in infection-prone vs. non-prone patients. Nasopharyngeal (NP) samples were collected from 74 acute otitis media (AOM) infection-prone and 754 non-prone children during 2094 healthy visits, 673 viral URI visits and 631 AOM visits. Three otopathogens Streptococcus pneumoniae (Spn), Nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis (Mcat) were identified by culture. NP colonization rates of multiple otopathogens during health were significantly lower than during viral URI, and during URI they were lower than at onset of upper respiratory bacterial infection in both AOM infection-prone and non-prone children. AOM infection-prone children had higher polymicrobial colonization rates than non-prone children during health, viral URI and AOM. Polymicrobial colonization rates of AOM infection-prone children during health were equivalent to that of non-prone children during viral URI, and during viral URI were equivalent to that of non-prone during AOM infection. Spn colonization was positively associated with NTHi and Mcat colonization during health, but negatively during AOM infection. The infection-prone patients more frequently have multiple potential bacterial pathogens in the NP than the non-prone patients. Polymicrobial interaction in the NP differs during health and at onset of infection. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  17. NKT cell depletion in humans during early HIV infection.

    Science.gov (United States)

    Fernandez, Caroline S; Kelleher, Anthony D; Finlayson, Robert; Godfrey, Dale I; Kent, Stephen J

    2014-08-01

    Natural killer T (NKT) cells bridge across innate and adaptive immune responses and have an important role in chronic viral infections such as human immunodeficiency virus (HIV). NKT cells are depleted during chronic HIV infection, but the timing, drivers and implications of this NKT cell depletion are poorly understood. We studied human peripheral blood NKT cell levels, phenotype and function in 31 HIV-infected subjects not on antiretroviral treatment from a mean of 4 months to 2 years after HIV infection. We found that peripheral CD4(+) NKT cells were substantially depleted and dysfunctional by 4 months after HIV infection. The depletion of CD4(+) NKT cells was more marked than the depletion of total CD4(+) T cells. Further, the early depletion of NKT cells correlated with CD4(+) T-cell decline, but not HIV viral levels. Levels of activated CD4(+) T cells correlated with the loss of NKT cells. Our studies suggest that the early loss of NKT cells is associated with subsequent immune destruction during HIV infection.

  18. [Immunotherapy for refractory viral infections].

    Science.gov (United States)

    Morio, Tomohiro; Fujita, Yuriko; Takahashi, Satoshi

    Various antiviral agents have been developed, which are sometimes associated with toxicity, development of virus-resistant strain, and high cost. Virus-specific T-cell (VST) therapy provides an alternative curative therapy that can be effective for a prolonged time without eliciting drug resistance. VSTs can be directly separated using several types of capture devices and can be obtained by stimulating peripheral blood mononuclear cells with viral antigens (virus, protein, or peptide) loaded on antigen-presenting cells (APC). APC can be transduced with virus-antigen coding plasmid or pulsed with overlapping peptides. VST therapy has been studied in drug non-responsive viral infections after hematopoietic cell transplantation (HCT). Several previous studies have demonstrated the efficacy of VST therapy without significant severe GVHD. In addition, VSTs from a third-party donor have been prepared and administered for post-HCT viral infection. Although target viruses of VSTs include herpes virus species and polyomavirus species, a wide variety of pathogens, such as papillomavirus, intracellular bacteria, and fungi, can be treated by pathogen-specific T-cells. Perhaps, these specific T-cells could be used for opportunistic infections in other immunocompromised hosts in the near future.

  19. Mutational analysis of varicella-zoster virus (VZV) immediate early protein (IE62) subdomains and their importance in viral replication

    Energy Technology Data Exchange (ETDEWEB)

    Khalil, Mohamed I., E-mail: mkhalil2@stanford.edu [Departments of Pediatrics and Microbiology & Immunology, Stan ford University School of Medicine, Stanford, CA (United States); Department of Molecular Biology, National Research Centre, El-Buhouth St., Cairo (Egypt); Che, Xibing; Sung, Phillip; Sommer, Marvin H. [Departments of Pediatrics and Microbiology & Immunology, Stan ford University School of Medicine, Stanford, CA (United States); Hay, John [Department of Microbiology and Immunology, School of Medicine and Biomedical Science, University at Buffalo, Buffalo, NY (United States); Arvin, Ann M. [Departments of Pediatrics and Microbiology & Immunology, Stan ford University School of Medicine, Stanford, CA (United States)

    2016-05-15

    VZV IE62 is an essential, immediate-early, tegument protein and consists of five domains. We generated recombinant viruses carrying mutations in the first three IE62 domains and tested their influence on VZV replication kinetics. The mutations in domain I did not affect replication kinetics while domain II mutations, disrupting the DNA binding and dimerization domain (DBD), were lethal for VZV replication. Mutations in domain III of the nuclear localization signal (NLS) and the two phosphorylation sites S686A/S722A resulted in slower growth in early and late infection respectively and were associated with IE62 accumulation in the cytoplasm and nucleus respectively. This study mapped the functional domains of IE62 in context of viral infection, indicating that DNA binding and dimerization domain is essential for VZV replication. In addition, the correct localization of IE62, whether nuclear or cytoplasmic, at different points in the viral life cycle, is important for normal progression of VZV replication. - Highlights: • Mutation of IE62 domain I did not affect VZV replication in melanoma cells. • IE62 domain II and III are important for VZV replication in melanoma cells. • Mutations of IE62 domain II (DBD) were lethal for virus replication. • Mutations of IE62 NLS and phosphorylation sites inhibited VZV replication. • NLS and S686A/S722A mutations altered localization of IE62 during early and late infection.

  20. Mutational analysis of varicella-zoster virus (VZV) immediate early protein (IE62) subdomains and their importance in viral replication

    International Nuclear Information System (INIS)

    Khalil, Mohamed I.; Che, Xibing; Sung, Phillip; Sommer, Marvin H.; Hay, John; Arvin, Ann M.

    2016-01-01

    VZV IE62 is an essential, immediate-early, tegument protein and consists of five domains. We generated recombinant viruses carrying mutations in the first three IE62 domains and tested their influence on VZV replication kinetics. The mutations in domain I did not affect replication kinetics while domain II mutations, disrupting the DNA binding and dimerization domain (DBD), were lethal for VZV replication. Mutations in domain III of the nuclear localization signal (NLS) and the two phosphorylation sites S686A/S722A resulted in slower growth in early and late infection respectively and were associated with IE62 accumulation in the cytoplasm and nucleus respectively. This study mapped the functional domains of IE62 in context of viral infection, indicating that DNA binding and dimerization domain is essential for VZV replication. In addition, the correct localization of IE62, whether nuclear or cytoplasmic, at different points in the viral life cycle, is important for normal progression of VZV replication. - Highlights: • Mutation of IE62 domain I did not affect VZV replication in melanoma cells. • IE62 domain II and III are important for VZV replication in melanoma cells. • Mutations of IE62 domain II (DBD) were lethal for virus replication. • Mutations of IE62 NLS and phosphorylation sites inhibited VZV replication. • NLS and S686A/S722A mutations altered localization of IE62 during early and late infection.

  1. Early-life disruption of amphibian microbiota decreases later-life resistance to parasites.

    Science.gov (United States)

    Knutie, Sarah A; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R

    2017-07-20

    Changes in the early-life microbiota of hosts might affect infectious disease risk throughout life, if such disruptions during formative times alter immune system development. Here, we test whether an early-life disruption of host-associated microbiota affects later-life resistance to infections by manipulating the microbiota of tadpoles and challenging them with parasitic gut worms as adults. We find that tadpole bacterial diversity is negatively correlated with parasite establishment in adult frogs: adult frogs that had reduced bacterial diversity as tadpoles have three times more worms than adults without their microbiota manipulated as tadpoles. In contrast, adult bacterial diversity during parasite exposure is not correlated with parasite establishment in adult frogs. Thus, in this experimental setup, an early-life disruption of the microbiota has lasting reductions on host resistance to infections, which is possibly mediated by its effects on immune system development. Our results support the idea that preventing early-life disruption of host-associated microbiota might confer protection against diseases later in life.Early-life microbiota alterations can affect infection susceptibility later in life, in animal models. Here, Knutie et al. show that manipulating the microbiota of tadpoles leads to increased susceptibility to parasitic infection in adult frogs, in the absence of substantial changes in the adults' microbiota.

  2. How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?

    Directory of Open Access Journals (Sweden)

    Carolin Vegvari

    Full Text Available Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements.

  3. Recycling Endosomes and Viral Infection.

    Science.gov (United States)

    Vale-Costa, Sílvia; Amorim, Maria João

    2016-03-08

    Many viruses exploit specific arms of the endomembrane system. The unique composition of each arm prompts the development of remarkably specific interactions between viruses and sub-organelles. This review focuses on the viral-host interactions occurring on the endocytic recycling compartment (ERC), and mediated by its regulatory Ras-related in brain (Rab) GTPase Rab11. This protein regulates trafficking from the ERC and the trans-Golgi network to the plasma membrane. Such transport comprises intricate networks of proteins/lipids operating sequentially from the membrane of origin up to the cell surface. Rab11 is also emerging as a critical factor in an increasing number of infections by major animal viruses, including pathogens that provoke human disease. Understanding the interplay between the ERC and viruses is a milestone in human health. Rab11 has been associated with several steps of the viral lifecycles by unclear processes that use sophisticated diversified host machinery. For this reason, we first explore the state-of-the-art on processes regulating membrane composition and trafficking. Subsequently, this review outlines viral interactions with the ERC, highlighting current knowledge on viral-host binding partners. Finally, using examples from the few mechanistic studies available we emphasize how ERC functions are adjusted during infection to remodel cytoskeleton dynamics, innate immunity and membrane composition.

  4. Evaluation of early recognition of viral infections in man. [using specific gravity of lymphocytes

    Science.gov (United States)

    Kelton, A. A.; Lawton, M. B.

    1975-01-01

    The potential of Lymphocyte Specific Gravity Distribution (LSGD) as a non-specific procedure for early diagnosis of viral disease in astronauts is considered. Results of experiments and a literature search show that several virus diseases result in distinctive changes in the specific gravity distribution of peripheral blood lymphocytes as a result of disease process and associated immune response. A tentative model is proposed which relates the shape of LSGD to the identity of subpopulations of peripheral lymphocytes in a preclinical viral disease situation.

  5. Adenovirus type 5 DNA-protein complexes from formaldehyde cross-linked cells early after infection

    International Nuclear Information System (INIS)

    Spector, David J.; Johnson, Jeffrey S.; Baird, Nicholas L.; Engel, Daniel A.

    2003-01-01

    We report here the properties of viral DNA-protein complexes that purify with cellular chromatin following formaldehyde cross-linking of intact cells early after infection. The cross-linked viral DNA fractionated into shear-sensitive (S) and shear- resistant (R) components that were separable by sedimentation, which allowed independent characterization. The R component had the density and sedimentation properties expected for DNA-protein complexes and contained intact viral DNA. It accounted for about 50% of the viral DNA recovered at 1.5 h after infection but less than 20% by 4.5 h. The proportion of R component was independent of multiplicity of infection, even at less than one particle per cell. Viral hexon and protein VII, but not protein VI, were detected in the fractions containing the R component. These properties are consistent with those of partially uncoated virions associated with the nuclear envelope. A substantial proportion of the S component viral DNA had the same density as cellular chromatin. Protein VII was the most abundant viral protein present in gradient fractions that contained the S component. Complexes containing USF transcription factor cross-linked to the adenovirus major late promoter were detected by viral chromatin immunoprecipitation of the fractions containing S component. The S component probably contained uncoated nuclear viral DNA that assembles into early viral transcription complexes

  6. Transmission of single and multiple viral variants in primary HIV-1 subtype C infection.

    Directory of Open Access Journals (Sweden)

    Vladimir Novitsky

    2011-02-01

    Full Text Available To address whether sequences of viral gag and env quasispecies collected during the early post-acute period can be utilized to determine multiplicity of transmitted HIV's, recently developed approaches for analysis of viral evolution in acute HIV-1 infection [1,2] were applied. Specifically, phylogenetic reconstruction, inter- and intra-patient distribution of maximum and mean genetic distances, analysis of Poisson fitness, shape of highlighter plots, recombination analysis, and estimation of time to the most recent common ancestor (tMRCA were utilized for resolving multiplicity of HIV-1 transmission in a set of viral quasispecies collected within 50 days post-seroconversion (p/s in 25 HIV-infected individuals with estimated time of seroconversion. The decision on multiplicity of HIV infection was made based on the model's fit with, or failure to explain, the observed extent of viral sequence heterogeneity. The initial analysis was based on phylogeny, inter-patient distribution of maximum and mean distances, and Poisson fitness, and was able to resolve multiplicity of HIV transmission in 20 of 25 (80% cases. Additional analysis involved distribution of individual viral distances, highlighter plots, recombination analysis, and estimation of tMRCA, and resolved 4 of the 5 remaining cases. Overall, transmission of a single viral variant was identified in 16 of 25 (64% cases, and transmission of multiple variants was evident in 8 of 25 (32% cases. In one case multiplicity of HIV-1 transmission could not be determined. In primary HIV-1 subtype C infection, samples collected within 50 days p/s and analyzed by a single-genome amplification/sequencing technique can provide reliable identification of transmission multiplicity in 24 of 25 (96% cases. Observed transmission frequency of a single viral variant and multiple viral variants were within the ranges of 64% to 68%, and 32% to 36%, respectively.

  7. APLASTIC ANEMIA ET CAUSA OF SUSPECT VIRAL HEPATITIS INFECTION: A CASE REPORT

    OpenAIRE

    I Wayan Wawan Lismana

    2014-01-01

    Aplastic anemia is anemia that occurs because of a failure of hematopoiesis is relatively rarebut can be life threatening. The cause of aplastic anemia itself is still largely unknown oridiopathic. Minority of cases mainly due to a virus infection, one of which is viral hepatitishas long been known to cause symptoms of aplastic anemia. This report discusses thesuspected aplastic anemia caused by hepatitis virus infection. Course of the disease or theprognosis of aplastic anemia varies, but a ...

  8. HIV infection and treatment: beyond viral control

    NARCIS (Netherlands)

    Sprenger, Herman

    2017-01-01

    Since 1996, Infection caused by the human immunodeficiency virus(HIV) can be successfully treated with a combination therapy of 3 antiviral drugs from 2 different classes. Life expectancy has increased dramatically by this treatment. Especially in the early years these combination therapies had many

  9. Prevalence of fibromyalgia among patients with chronic hepatitis C infection: relationship to viral characteristics and quality of life.

    Science.gov (United States)

    Mohammad, Ausaf; Carey, John J; Storan, Eoin; Scarry, Margaret; Coughlan, Robert J; Lee, John M

    2012-01-01

    We determined the prevalence of fibromyalgia syndrome (FMS) in a cohort of subjects with chronic hepatitis C virus (HCV), and the relationship to subject demographics, viral characteristics, and quality of life. In a cross-sectional study of a cohort of HCV-infected individuals, all subjects underwent a standard assessment including history, clinical examination, and functional assessments for pain and disability. A total of 185 subjects met the inclusion criteria. Median age was 48.7 years, and 110 (59%) were women. A total of 106 (57%) of the subjects met criteria for the presence of FMS. Widespread pain and ≥11 tender points were present in all of the subjects with FMS, fatigue in 98 (92%), and depression in 60 (57%). Among those with FMS, mean pain score was 70±11.78 and 36% reported some functional impairment on (HAQ-DI>0), with 17% reporting moderate-to-severe functional impairment (HAQ-DI≥1.5). This study reveals a high prevalence of FMS (57%) among subjects with chronic HCV infection, one third of whom reported some degree of functional impairment. Recognition and management of this condition in such patients will help improve their quality of life.

  10. Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity

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    Geovanny F. Perez

    2016-10-01

    Full Text Available Premature children are prone to severe viral respiratory infections in early life, but the age at which susceptibility peaks and disappears for each pathogen is unclear. Methods: A retrospective analysis was performed of the age distribution and clinical features of acute viral respiratory infections in full-term and premature children, aged zero to seven years. Results: The study comprised of a total of 630 hospitalizations (n = 580 children. Sixty-seven percent of these hospitalizations occurred in children born full-term (>37 weeks, 12% in preterm (32–37 weeks and 21% in severely premature children (<32 weeks. The most common viruses identified were rhinovirus (RV; 60% and respiratory syncytial virus (RSV; 17%. Age-distribution analysis of each virus identified that severely premature children had a higher relative frequency of RV and RSV in their first three years, relative to preterm or full-term children. Additionally, the probability of RV- or RSV-induced wheezing was higher overall in severely premature children less than three years old. Conclusions: Our results indicate that the vulnerability to viral infections in children born severely premature is more specific for RV and RSV and persists during the first three years of age. Further studies are needed to elucidate the age-dependent molecular mechanisms that underlie why premature infants develop RV- and RSV-induced wheezing in early life.

  11. Management of Viral Central Nervous System Infections: A Primer for Clinicians

    Directory of Open Access Journals (Sweden)

    P Brandon Bookstaver

    2017-04-01

    Full Text Available Viruses are a common cause of central nervous system (CNS infections with many host, agent, and environmental factors influencing the expression of viral diseases. Viruses can be responsible for CNS disease through a variety of mechanisms including direct infection and replication within the CNS resulting in encephalitis, infection limited to the meninges, or immune-related processes such as acute disseminated encephalomyelitis. Common pathogens including herpes simplex virus, varicella zoster, and enterovirus are responsible for the greatest number of cases in immunocompetent hosts. Other herpes viruses (eg, cytomegalovirus, John Cunningham virus are more common in immunocompromised hosts. Arboviruses such as Japanese encephalitis virus and Zika virus are important pathogens globally, but the prevalence varies significantly by geographic region and often season. Early diagnosis from radiographic evidence and molecular (eg, rapid diagnostics is important for targeted therapy. Antivirals may be used effectively against some pathogens, although several viruses have no effective treatment. This article provides a review of epidemiology, diagnostics, and management of common viral pathogens in CNS disease.

  12. Hepatic transcriptome analysis of hepatitis C virus infection in chimpanzees defines unique gene expression patterns associated with viral clearance.

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    Santosh Nanda

    Full Text Available Hepatitis C virus infection leads to a high rate of chronicity. Mechanisms of viral clearance and persistence are still poorly understood. In this study, hepatic gene expression analysis was performed to identify any molecular signature associated with the outcome of hepatitis C virus (HCV infection in chimpanzees. Acutely HCV-infected chimpanzees with self-limited infection or progression to chronicity were studied. Interferon stimulated genes were induced irrespective of the outcome of infection. Early induction of a set of genes associated with cell proliferation and immune activation was associated with subsequent viral clearance. Specifically, two of the genes: interleukin binding factor 3 (ILF3 and cytotoxic granule-associated RNA binding protein (TIA1, associated with robust T-cell response, were highly induced early in chimpanzees with self-limited infection. Up-regulation of genes associated with CD8+ T cell response was evident only during the clearance phase of the acute self-limited infection. The induction of these genes may represent an initial response of cellular injury and proliferation that successfully translates to a "danger signal" leading to induction of adaptive immunity to control viral infection. This primary difference in hepatic gene expression between self-limited and chronic infections supports the concept that successful activation of HCV-specific T-cell response is critical in clearance of acute HCV infection.

  13. Human Antiviral Protein IFIX Suppresses Viral Gene Expression during Herpes Simplex Virus 1 (HSV-1) Infection and Is Counteracted by Virus-induced Proteasomal Degradation.

    Science.gov (United States)

    Crow, Marni S; Cristea, Ileana M

    2017-04-01

    The interferon-inducible protein X (IFIX), a member of the PYHIN family, was recently recognized as an antiviral factor against infection with herpes simplex virus 1 (HSV-1). IFIX binds viral DNA upon infection and promotes expression of antiviral cytokines. How IFIX exerts its host defense functions and whether it is inhibited by the virus remain unknown. Here, we integrated live cell microscopy, proteomics, IFIX domain characterization, and molecular virology to investigate IFIX regulation and antiviral functions during HSV-1 infection. We find that IFIX has a dynamic localization during infection that changes from diffuse nuclear and nucleoli distribution in uninfected cells to discrete nuclear puncta early in infection. This is rapidly followed by a reduction in IFIX protein levels. Indeed, using immunoaffinity purification and mass spectrometry, we define IFIX interactions during HSV-1 infection, finding an association with a proteasome subunit and proteins involved in ubiquitin-proteasome processes. Using synchronized HSV-1 infection, microscopy, and proteasome-inhibition experiments, we demonstrate that IFIX co-localizes with nuclear proteasome puncta shortly after 3 h of infection and that its pyrin domain is rapidly degraded in a proteasome-dependent manner. We further demonstrate that, in contrast to several other host defense factors, IFIX degradation is not dependent on the E3 ubiquitin ligase activity of the viral protein ICP0. However, we show IFIX degradation requires immediate-early viral gene expression, suggesting a viral host suppression mechanism. The IFIX interactome also demonstrated its association with transcriptional regulatory proteins, including the 5FMC complex. We validate this interaction using microscopy and reciprocal isolations and determine it is mediated by the IFIX HIN domain. Finally, we show IFIX suppresses immediate-early and early viral gene expression during infection. Altogether, our study demonstrates that IFIX antiviral

  14. Early life vaccination

    DEFF Research Database (Denmark)

    Nazerai, Loulieta; Bassi, Maria Rosaria; Uddbäck, Ida Elin Maria

    2016-01-01

    Intracellular pathogens represent a serious threat during early life. Importantly, even though the immune system of newborns may be characterized as developmentally immature, with a propensity to develop Th2 immunity, significant CD8+ T-cell responses may still be elicited in the context of optimal...... the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo...... cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate...

  15. The ins and outs of eukaryotic viruses: Knowledge base and ontology of a viral infection.

    Directory of Open Access Journals (Sweden)

    Chantal Hulo

    Full Text Available Viruses are genetically diverse, infect a wide range of tissues and host cells and follow unique processes for replicating themselves. All these processes were investigated and indexed in ViralZone knowledge base. To facilitate standardizing data, a simple ontology of viral life-cycle terms was developed to provide a common vocabulary for annotating data sets. New terminology was developed to address unique viral replication cycle processes, and existing terminology was modified and adapted. The virus life-cycle is classically described by schematic pictures. Using this ontology, it can be represented by a combination of successive terms: "entry", "latency", "transcription", "replication" and "exit". Each of these parts is broken down into discrete steps. For example Zika virus "entry" is broken down in successive steps: "Attachment", "Apoptotic mimicry", "Viral endocytosis/ macropinocytosis", "Fusion with host endosomal membrane", "Viral factory". To demonstrate the utility of a standard ontology for virus biology, this work was completed by annotating virus data in the ViralZone, UniProtKB and Gene Ontology databases.

  16. Redox Imbalance and Viral Infections in Neurodegenerative Diseases

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    Dolores Limongi

    2016-01-01

    Full Text Available Reactive oxygen species (ROS are essential molecules for many physiological functions and act as second messengers in a large variety of tissues. An imbalance in the production and elimination of ROS is associated with human diseases including neurodegenerative disorders. In the last years the notion that neurodegenerative diseases are accompanied by chronic viral infections, which may result in an increase of neurodegenerative diseases progression, emerged. It is known in literature that enhanced viral infection risk, observed during neurodegeneration, is partly due to the increase of ROS accumulation in brain cells. However, the molecular mechanisms of viral infection, occurring during the progression of neurodegeneration, remain unclear. In this review, we discuss the recent knowledge regarding the role of influenza, herpes simplex virus type-1, and retroviruses infection in ROS/RNS-mediated Parkinson’s disease (PD, Alzheimer’s disease (AD, and amyotrophic lateral sclerosis (ALS.

  17. Viral RNA Degradation and Diffusion Act as a Bottleneck for the Influenza A Virus Infection Efficiency.

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    Max Schelker

    2016-10-01

    Full Text Available After endocytic uptake, influenza viruses transit early endosomal compartments and eventually reach late endosomes. There, the viral glycoprotein hemagglutinin (HA triggers fusion between endosomal and viral membrane, a critical step that leads to release of the viral segmented genome destined to reach the cell nucleus. Endosomal maturation is a complex process involving acidification of the endosomal lumen as well as endosome motility along microtubules. While the pH drop is clearly critical for the conformational change and membrane fusion activity of HA, the effect of intracellular transport dynamics on the progress of infection remains largely unclear. In this study, we developed a comprehensive mathematical model accounting for the first steps of influenza virus infection. We calibrated our model with experimental data and challenged its predictions using recombinant viruses with altered pH sensitivity of HA. We identified the time point of virus-endosome fusion and thereby the diffusion distance of the released viral genome to the nucleus as a critical bottleneck for efficient virus infection. Further, we concluded and supported experimentally that the viral RNA is subjected to cytosolic degradation strongly limiting the probability of a successful genome import into the nucleus.

  18. Cytopathic bovine viral diarrhea viruses (BVDV): emerging pestiviruses doomed to extinction.

    Science.gov (United States)

    Peterhans, Ernst; Bachofen, Claudia; Stalder, Hanspeter; Schweizer, Matthias

    2010-01-01

    Bovine viral diarrhea virus (BVDV), a Flaviviridae pestivirus, is arguably one of the most widespread cattle pathogens worldwide. Each of its two genotypes has two biotypes, non-cytopathic (ncp) and cytopathic (cp). Only the ncp biotype of BVDV may establish persistent infection in the fetus when infecting a dam early in gestation, a time point which predates maturity of the adaptive immune system. Such fetuses may develop and be born healthy but remain infected for life. Due to this early initiation of fetal infection and to the expression of interferon antagonistic proteins, persistently infected (PI) animals remain immunotolerant to the infecting viral strain. Although only accounting for some 1% of all animals in regions where BVDV is endemic, PI animals ensure the viral persistence in the host population. These animals may, however, develop the fatal mucosal disease, which is characterized by widespread lesions in the gastrointestinal tract. Cp BVD virus, in addition to the persisting ncp biotype, can be isolated from such animals. The cp viruses are characterized by unrestrained genome replication, and their emergence from the persisting ncp ones is due to mutations that are unique in each virus analyzed. They include recombinations with host cell mRNA, gene translocations and duplications, and point mutations. Cytopathic BVD viruses fail to establish chains of infection and are unable to cause persistent infection. Hence, these viruses illustrate a case of "viral emergence to extinction" - irrelevant for BVDV evolution, but fatal for the PI host. © INRA, EDP Sciences, 2010.

  19. Viral Infections in Pregnancy: A Focus on Ebola Virus.

    Science.gov (United States)

    Olgun, Nicole S

    2018-01-30

    During gestation, the immune response of the placenta to viruses and other pathogens plays an important role in determining a pregnant woman's vulnerability toward infectious diseases. Located at the maternal- fetal interface, trophoblast cells serve to minimize the spread of viruses between the host and developing fetus through an intricate system of innate antiviral immune signaling. Adverse pregnancy outcomes, ranging from learning disabilities to preterm birth and fetal death, are all documented results of a viral breach in the placental barrier. Viral infections during pregnancy can also be spread through blood and vaginal secretions, and during the post-natal period, via breast milk. Thus, even in the absence of vertical transmission of viral infection to the fetus, maternal health can still be compromised and threaten the pregnancy. The most common viral DNA isolates found in gestation are adenovirus, cytomegalovirus, and enterovirus. However, with the recent pandemic of Ebola virus, and the first documented case of a neonate to survive due to experimental therapies in 2017, it is becoming increasingly apparent that the changing roles and impacts of viral infection during pregnancy needs to be better understood, while strategies to minimize adverse pregnancy outcomes need to be identified. This review focuses on the adverse impacts of viral infection during gestation, with an emphasis on Ebola virus. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. The Immunoproteasome and Viral Infection: A Complex Regulator of Inflammation

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    Mary Katherine McCarthy

    2015-01-01

    Full Text Available During viral infection, proper regulation of immune responses is necessary to ensure successful viral clearance with minimal host tissue damage. Proteasomes play a crucial role in the generation of antigenic peptides for presentation on MHC class I molecules, and thus activation of CD8 T cells, as well as activation of the NF-kB pathway. A specialized type of proteasome called the immunoproteasome is constitutively expressed in hematopoietic cells and induced in nonimmune cells during viral infection by interferon (IFN signaling. The immunoproteasome regulates CD8 T cell responses to many viral epitopes during infection. Accumulating evidence suggests that the immunoproteasome may also contribute to regulation of proinflammatory cytokine production, activation of the NF-kB pathway, and management of oxidative stress. Many viruses have mechanisms of interfering with immunoproteasome function, including prevention of transcriptional upregulation of immunoproteasome components as well as direct interaction of viral proteins with immunoproteasome subunits. A better understanding of the role of the immunoproteasome in different cell types, tissues, and hosts has the potential to improve vaccine design and facilitate the development of effective treatment strategies for viral infections.

  1. Exercise Improves Host Response to Influenza Viral Infection in Obese and Non-Obese Mice through Different Mechanisms

    Science.gov (United States)

    Warren, Kristi J.; Olson, Molly M.; Thompson, Nicholas J.; Cahill, Mackenzie L.; Wyatt, Todd A.; Yoon, Kyoungjin J.; Loiacono, Christina M.; Kohut, Marian L.

    2015-01-01

    Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression. In non-obese mice, exercise treatment reduced lung viral load, increased Type-I-IFN-related gene expression early during infection, but reduced BAL inflammatory cytokines and chemokines. In both obese and non-obese mice, exercise increased serum anti-influenza virus specific IgG2c antibody, increased CD8+ T cell percentage in BAL, and reduced TNFα by influenza viral NP-peptide-responding CD8+ T cells. Overall, the results suggest that exercise “restores” the immune response of obese mice to a phenotype similar to non-obese mice by improving the delay in immune activation. In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response. PMID:26110868

  2. Plasma Viral miRNAs Indicate a High Prevalence of Occult Viral Infections

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    Enrique Fuentes-Mattei

    2017-06-01

    Full Text Available Prevalence of Kaposi sarcoma-associated herpesvirus (KSHV/HHV-8 varies greatly in different populations. We hypothesized that the actual prevalence of KSHV/HHV8 infection in humans is underestimated by the currently available serological tests. We analyzed four independent patient cohorts with post-surgical or post-chemotherapy sepsis, chronic lymphocytic leukemia and post-surgical patients with abdominal surgical interventions. Levels of specific KSHV-encoded miRNAs were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR, and KSHV/HHV-8 IgG were measured by immunoassay. We also measured specific miRNAs from Epstein Barr Virus (EBV, a virus closely related to KSHV/HHV-8, and determined the EBV serological status by ELISA for Epstein-Barr nuclear antigen 1 (EBNA-1 IgG. Finally, we identified the viral miRNAs by in situ hybridization (ISH in bone marrow cells. In training/validation settings using independent multi-institutional cohorts of 300 plasma samples, we identified in 78.50% of the samples detectable expression of at least one of the three tested KSHV-miRNAs by RT-qPCR, while only 27.57% of samples were found to be seropositive for KSHV/HHV-8 IgG (P < 0.001. The prevalence of KSHV infection based on miRNAs qPCR is significantly higher than the prevalence determined by seropositivity, and this is more obvious for immuno-depressed patients. Plasma viral miRNAs quantification proved that EBV infection is ubiquitous. Measurement of viral miRNAs by qPCR has the potential to become the “gold” standard method to detect certain viral infections in clinical practice.

  3. Staphylococcus aureus α-toxin modulates skin host response to viral infection.

    Science.gov (United States)

    Bin, Lianghua; Kim, Byung Eui; Brauweiler, Anne; Goleva, Elena; Streib, Joanne; Ji, Yinduo; Schlievert, Patrick M; Leung, Donald Y M

    2012-09-01

    Patients with atopic dermatitis (AD) with a history of eczema herpeticum have increased staphylococcal colonization and infections. However, whether Staphylococcus aureus alters the outcome of skin viral infection has not been determined. We investigated whether S aureus toxins modulated host response to herpes simplex virus (HSV) 1 and vaccinia virus (VV) infections in normal human keratinocytes (NHKs) and in murine infection models. NHKs were treated with S aureus toxins before incubation of viruses. BALB/c mice were inoculated with S aureus 2 days before VV scarification. Viral loads of HSV-1 and VV were evaluated by using real-time PCR, a viral plaque-forming assay, and immunofluorescence staining. Small interfering RNA duplexes were used to knockdown the gene expression of the cellular receptor of α-toxin, a disintegrin and metalloprotease 10 (ADAM10). ADAM10 protein and α-toxin heptamers were detected by using Western blot assays. We demonstrate that sublytic staphylococcal α-toxin increases viral loads of HSV-1 and VV in NHKs. Furthermore, we demonstrate in vivo that the VV load is significantly greater (P skin inoculated with an α-toxin-producing S aureus strain compared with murine skin inoculated with the isogenic α-toxin-deleted strain. The viral enhancing effect of α-toxin is mediated by ADAM10 and is associated with its pore-forming property. Moreover, we demonstrate that α-toxin promotes viral entry in NHKs. The current study introduces the novel concept that staphylococcal α-toxin promotes viral skin infection and provides a mechanism by which S aureus infection might predispose the host toward disseminated viral infections. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  4. Lymphocytes Negatively Regulate NK Cell Activity via Qa-1b following Viral Infection

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    Haifeng C. Xu

    2017-11-01

    Full Text Available NK cells can reduce anti-viral T cell immunity during chronic viral infections, including infection with the lymphocytic choriomeningitis virus (LCMV. However, regulating factors that maintain the equilibrium between productive T cell and NK cell immunity are poorly understood. Here, we show that a large viral load resulted in inhibition of NK cell activation, which correlated with increased expression of Qa-1b, a ligand for inhibitory NK cell receptors. Qa-1b was predominantly upregulated on B cells following LCMV infection, and this upregulation was dependent on type I interferons. Absence of Qa-1b resulted in increased NK cell-mediated regulation of anti-viral T cells following viral infection. Consequently, anti-viral T cell immunity was reduced in Qa-1b- and NKG2A-deficient mice, resulting in increased viral replication and immunopathology. NK cell depletion restored anti-viral immunity and virus control in the absence of Qa-1b. Taken together, our findings indicate that lymphocytes limit NK cell activity during viral infection in order to promote anti-viral T cell immunity.

  5. Dengue viral infections

    OpenAIRE

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing...

  6. Viral-specific T-cell transfer from HSCT donor for the treatment of viral infections or diseases after HSCT.

    Science.gov (United States)

    Qian, C; Wang, Y; Reppel, L; D'aveni, M; Campidelli, A; Decot, V; Bensoussan, D

    2018-02-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for treatment of some malignant and non-malignant hematological diseases. However, post-HSCT patients are severely immunocompromised and susceptible to viral infections, which are a major cause of morbidity and mortality. Although antiviral agents are now available for most types of viral infections, they are not devoid of side effects and their efficacy is limited when there is no concomitant antiviral immune reconstitution. In recent decades, adoptive transfer of viral-specific T cells (VSTs) became an alternative treatment for viral infection after HSCT. However, two major issues are concerned in VST transfer: the risk of GVHD and antiviral efficacy. We report an exhaustive review of the published studies that focus on prophylactic and/or curative therapy by donor VST transfer for post-HSCT common viral infections. A low incidence of GVHD and a good antiviral efficacy was observed after adoptive transfer of VSTs from HSCT donor. Viral-specific T-cell transfer is a promising approach for a broad clinical application. Nevertheless, a randomized controlled study in a large cohort of patients comparing antiviral treatment alone to antiviral treatment combined with VSTs is still needed to demonstrate efficacy and safety.

  7. Early Epstein-Barr Virus Genomic Diversity and Convergence toward the B95.8 Genome in Primary Infection.

    Science.gov (United States)

    Weiss, Eric R; Lamers, Susanna L; Henderson, Jennifer L; Melnikov, Alexandre; Somasundaran, Mohan; Garber, Manuel; Selin, Liisa; Nusbaum, Chad; Luzuriaga, Katherine

    2018-01-15

    Over 90% of the world's population is persistently infected with Epstein-Barr virus. While EBV does not cause disease in most individuals, it is the common cause of acute infectious mononucleosis (AIM) and has been associated with several cancers and autoimmune diseases, highlighting a need for a preventive vaccine. At present, very few primary, circulating EBV genomes have been sequenced directly from infected individuals. While low levels of diversity and low viral evolution rates have been predicted for double-stranded DNA (dsDNA) viruses, recent studies have demonstrated appreciable diversity in common dsDNA pathogens (e.g., cytomegalovirus). Here, we report 40 full-length EBV genome sequences obtained from matched oral wash and B cell fractions from a cohort of 10 AIM patients. Both intra- and interpatient diversity were observed across the length of the entire viral genome. Diversity was most pronounced in viral genes required for establishing latent infection and persistence, with appreciable levels of diversity also detected in structural genes, including envelope glycoproteins. Interestingly, intrapatient diversity declined significantly over time ( P < 0.01), and this was particularly evident on comparison of viral genomes sequenced from B cell fractions in early primary infection and convalescence ( P < 0.001). B cell-associated viral genomes were observed to converge, becoming nearly identical to the B95.8 reference genome over time (Spearman rank-order correlation test; r = -0.5589, P = 0.0264). The reduction in diversity was most marked in the EBV latency genes. In summary, our data suggest independent convergence of diverse viral genome sequences toward a reference-like strain within a relatively short period following primary EBV infection. IMPORTANCE Identification of viral proteins with low variability and high immunogenicity is important for the development of a protective vaccine. Knowledge of genome diversity within circulating viral

  8. [Viral respiratory co-infections in pediatric patients admitted for acute respiratory infection and their impact on clinical severity].

    Science.gov (United States)

    Martínez, Pamela; Cordero, Jaime; Valverde, Cristián; Unanue, Nancy; Dalmazzo, Roberto; Piemonte, Paula; Vergara, Ivonne; Torres, Juan P

    2012-04-01

    Respiratory viruses are the leading cause of acute respiratory tract infection (ARI) in children. It has been reported that viral respiratory co-infection could be associated with severe clinical course. To describe the frequency of viral co-infection in children admitted for AlRI and evaluate whether this co-infection was associated with more severe clinical course. Prospective, descriptive study in pediatric patients who were hospitalized for ARI, with molecular detection of at least 1 respiratory virus in nasopharyngeal sample studied by PCR-Microarray for 17 respiratory viruses. 110 out of 147 patients with detection of > 1 respiratory virus were included. Viral co-infection was detected in 41/110 (37%). 22/110 children (20%) were classified as moderate to severe clinical course and 88/110 (80%) were classified as mild clinical course. In the group of moderate to severe clinical course, viral respiratory co-infection was detected in 6/22 (27.3%), compared to 35/88 (39.8 %) in the mild clinical course group. No statistically significant difference was found regarding the presence of co-infection between groups (p = 0.33). We detected high rates of viral co-infection in children with ARI. It was not possible to demonstrate that viral co-infections were related with severe clinical course in hospitalized children.

  9. Acute hepatitis e viral infection in pregnancy and maternal morbidity

    International Nuclear Information System (INIS)

    Khaskheli, M.N.; Baloch, S.

    2015-01-01

    To determine the maternal morbidity in pregnant women with acute hepatitis E viral infection. Study Design: Observational, cross-sectional study. Place and Duration of Study: Departments of Obstetrics and Gynaecology and Medicine, Liaquat University of Medical and Health Sciences, Jamshoro, Red Crescent General Hospital and Saint Elizabeth Hospital, Hyderabad, from January 2011 to December 2013. Methodology: The study population was pregnant women with acute hepatitis E infection confirmed by ELIZA technique. Pregnant women with other hepatic viral infections were excluded. All medical and obstetric conditions, and mortality were noted on the predesigned proforma. Results: Out of the total 45 admitted pregnant women with hepatitis E viral infection, 22 women (48.9%) had severe morbidity. The most common were hepatic coma in 8 (36.36%) cases and disseminated intravascular coagulation in 14 (63.63%) cases. Highest mortality rate was seen in women with hepatic coma (100%), while in those with disseminated intravascular coagulation, one out of the 14 cases (7.14%) died. Conclusion: The acute viral hepatitis E infection in pregnant women is associated with maternal morbidities and high mortality rate. (author)

  10. Graft-versus-host disease and sialodacryoadenitis viral infection in bone marrow transplanted rats

    International Nuclear Information System (INIS)

    Rossie, K.M.; Sheridan, J.F.; Barthold, S.W.; Tutschka, P.J.

    1988-01-01

    The effect of a localized viral infection on the occurrence of graft-vs.-host disease (GVHD) was examined in allogeneic rat bone marrow chimeras (ACI/LEW). Animals without clinical evidence of GVHD, 62 days after bone marrow transplant, were infected in salivary and lacrimal glands with sialodacryoadenitis virus (SDAV), and sacrificed 8-25 days postinfection. Using established histologic criteria, GVHD was found more frequently in salivary and lacrimal glands of SDAV-infected chimeras than uninfected chimeras. Skin and oral mucosa, tissues not infected by the virus, showed no differences in occurrence of GVHD, suggesting that the viral infection induced only local and not systemic GVHD. GVHD and SDAV infection, which are histologically similar, were differentiated by examining tissues for SDAV antigen using immunoperoxidase technique. Histologic changes were present for at least 1 week longer than viral antigen, suggesting they represented GVHD rather than viral infection. GVHD and SDAV infection were also differentiated by looking for a histologic feature characteristic of GVHD and not found in SDAV infection (periductal lymphocytic infiltrate). This was found in SDAV-infected chimeras more frequently than uninfected chimeras, suggesting that the viral infection somehow induced GVHD. Results showed a localized increase in the occurrence of GVHD subsequent to localized viral infection

  11. Dengue viral infections

    OpenAIRE

    Gurugama Padmalal; Garg Pankaj; Perera Jennifer; Wijewickrama Ananda; Seneviratne Suranjith

    2010-01-01

    Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF) occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host...

  12. Uncovering Viral Protein-Protein Interactions and their Role in Arenavirus Life Cycle

    Directory of Open Access Journals (Sweden)

    Nora López

    2012-09-01

    Full Text Available The Arenaviridae family includes widely distributed pathogens that cause severe hemorrhagic fever in humans. Replication and packaging of their single-stranded RNA genome involve RNA recognition by viral proteins and a number of key protein-protein interactions. Viral RNA synthesis is directed by the virus-encoded RNA dependent-RNA polymerase (L protein and requires viral RNA encapsidation by the Nucleoprotein. In addition to the role that the interaction between L and the Nucleoprotein may have in the replication process, polymerase activity appears to be modulated by the association between L and the small multifunctional Z protein. Z is also a structural component of the virions that plays an essential role in viral morphogenesis. Indeed, interaction of the Z protein with the Nucleoprotein is critical for genome packaging. Furthermore, current evidence suggests that binding between Z and the viral envelope glycoprotein complex is required for virion infectivity, and that Z homo-oligomerization is an essential step for particle assembly and budding. Efforts to understand the molecular basis of arenavirus life cycle have revealed important details on these viral protein-protein interactions that will be reviewed in this article.

  13. ASTHMA AND VIRAL INFECTIONS IN CHILDREN

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    D. Sh. Macharadze

    2014-01-01

    Full Text Available Viruses are the most common pathogens of acute respiratory diseases — most often causing mild symptoms of common cold: cough, runny nose, temperature increases. At the same time, 1/3 of children have the following symptoms of lower respiratory tract disorders: shortness of breath, wheezing, coughing, respiratory failure. Virus-induced wheezing are risk factors for development of asthma in childhood. Recent clinical and scientific data suggest: the more difficult are viral respiratory infections in young children, the higher their risk of asthma later on. Another feature is that children with allergic diseases are much more likely to have viral respiratory infections(and with longer clinical course, compared with children without atopy. The use of ibuprofen is safe for children over 3 months, including suffering from bronchial asthma.

  14. The susceptible-infected-recovered (SIR) model for viral marketing

    Science.gov (United States)

    Ismail, Siti Suhaila; Akil, Ku Azlina Ku; Chulan, Majdah; Sharif, Noorzila

    2017-11-01

    Viral marketing is a marketing strategy utilizes social media to spread information about a product or services provided. It is the most powerful way to share information in a short amount of time. The objective of this study is to investigate the dynamic of viral marketing within a time duration in the point of view of mathematics. This study used the epidemiological model known as Susceptible-Infected-Recovered (SIR). The model consists of a system of three differential equations with three state variables namely susceptible (S), infected (I) and recovered (R). It considers a case of SIR model with demography. Numerical experiments have been performed. The results show that viral marketing reaches its peak within two days. The online messages shared will become higher if the initial number of the infected individual has been increased.

  15. Viral vs. bacterial pulmonary infections in chidren. Is roentgenographic differentiation possible

    International Nuclear Information System (INIS)

    Swischuk, L.E.; Hayden, C.K. Jr.

    1986-01-01

    This study was conducted to determine whether one could identify viral and bacterial pulmonary infections with confidence. It has been our impression for some time that one could differentiate viral from bacterial pulmonary infections on the basis of roentgenographic findings alone and test this hypothesis, we conducted this study where the roentgenographic findings first were categorized as being due to viral or bacterial infection and then compared with clinical results. The overall accuracy was just over 90% and our method of analysis is presented. (orig.)

  16. Roles of the Picornaviral 3C Proteinase in the Viral Life Cycle and Host Cells

    Directory of Open Access Journals (Sweden)

    Di Sun

    2016-03-01

    Full Text Available The Picornaviridae family comprises a large group of non-enveloped viruses that have a major impact on human and veterinary health. The viral genome contains one open reading frame encoding a single polyprotein that can be processed by viral proteinases. The crucial 3C proteinases (3Cpros of picornaviruses share similar spatial structures and it is becoming apparent that 3Cpro plays a significant role in the viral life cycle and virus host interaction. Importantly, the proteinase and RNA-binding activity of 3Cpro are involved in viral polyprotein processing and the initiation of viral RNA synthesis. In addition, 3Cpro can induce the cleavage of certain cellular factors required for transcription, translation and nucleocytoplasmic trafficking to modulate cell physiology for viral replication. Due to interactions between 3Cpro and these essential factors, 3Cpro is also involved in viral pathogenesis to support efficient infection. Furthermore, based on the structural conservation, the development of irreversible inhibitors and discovery of non-covalent inhibitors for 3Cpro are ongoing and a better understanding of the roles played by 3Cpro may provide insights into the development of potential antiviral treatments. In this review, the current knowledge regarding the structural features, multiple functions in the viral life cycle, pathogen host interaction, and development of antiviral compounds for 3Cpro is summarized.

  17. Viral and cellular subnuclear structures in human cytomegalovirus-infected cells.

    Science.gov (United States)

    Strang, Blair L

    2015-02-01

    In human cytomegalovirus (HCMV)-infected cells, a dramatic remodelling of the nuclear architecture is linked to the creation, utilization and manipulation of subnuclear structures. This review outlines the involvement of several viral and cellular subnuclear structures in areas of HCMV replication and virus-host interaction that include viral transcription, viral DNA synthesis and the production of DNA-filled viral capsids. The structures discussed include those that promote or impede HCMV replication (such as viral replication compartments and promyelocytic leukaemia nuclear bodies, respectively) and those whose role in the infected cell is unclear (for example, nucleoli and nuclear speckles). Viral and cellular proteins associated with subnuclear structures are also discussed. The data reviewed here highlight advances in our understanding of HCMV biology and emphasize the complexity of HCMV replication and virus-host interactions in the nucleus. © 2015 The Authors.

  18. Cytotoxic CD4 T Cells—Friend or Foe during Viral Infection?

    Science.gov (United States)

    Juno, Jennifer A.; van Bockel, David; Kent, Stephen J.; Kelleher, Anthony D.; Zaunders, John J.; Munier, C. Mee Ling

    2017-01-01

    CD4 T cells with cytotoxic function were once thought to be an artifact due to long-term in vitro cultures but have in more recent years become accepted and reported in the literature in response to a number of viral infections. In this review, we focus on cytotoxic CD4 T cells in the context of human viral infections and in some infections that affect mice and non-human primates. We examine the effector mechanisms used by cytotoxic CD4 cells, the phenotypes that describe this population, and the transcription factors and pathways that lead to their induction following infection. We further consider the cells that are the predominant targets of this effector subset and describe the viral infections in which CD4 cytotoxic T lymphocytes have been shown to play a protective or pathologic role. Cytotoxic CD4 T cells are detected in the circulation at much higher levels than previously realized and are now recognized to have an important role in the immune response to viral infections. PMID:28167943

  19. Examination of the early infection stages of koi herpesvirus (KHV) in experimentally infected carp, Cyprinus carpio L. using in situ hybridization.

    Science.gov (United States)

    Monaghan, S J; Thompson, K D; Adams, A; Kempter, J; Bergmann, S M

    2015-05-01

    Koi herpesvirus (KHV) causes a highly infectious disease afflicting common carp and koi, Cyprinus carpio L. Various molecular and antibody-based detection methods have been used to elucidate the rapid attachment and dissemination of the virus throughout carp tissues, facilitating ongoing development of effective diagnostic approaches. In situ hybridization (ISH) was used here to determine the target tissues of KHV during very early infection, after infecting carp with a highly virulent KHV isolate. Analysis of paraffin-embedded tissues (i.e. gills, skin, spleen, kidney, gut, liver and brain) during the first 8 h and following 10 days post-infection (hpi; dpi) revealed positive signals in skin mucus, gills and gut sections after only 1 hpi. Respiratory epithelial cells were positive as early as 2 hpi. Viral DNA was also detected within blood vessels of various tissues early in the infection. Notable increases in signal abundance were observed in the gills and kidney between 5 and 10 dpi, and viral DNA was detected in all tissues except brain. This study suggests that the gills and gut play an important role in the early pathogenesis of this Alloherpesvirus, in addition to skin, and demonstrates ISH as a useful diagnostic tool for confirmation of acutely infected carp. © 2014 John Wiley & Sons Ltd.

  20. Gefitinib and pyrrolidine dithiocarbamate decrease viral replication and cytokine production in dengue virus infected human monocyte cultures.

    Science.gov (United States)

    Duran, Anyelo; Valero, Nereida; Mosquera, Jesús; Fuenmayor, Edgard; Alvarez-Mon, Melchor

    2017-12-15

    The epidermal growth factor receptor (EGFR) and nucleotide-binding and oligomerization-domain containing 2 (NOD2) are important in cancer and in microbial recognition, respectively. These molecules trigger intracellular signaling pathways inducing the expression of inflammatory genes by NF-kB translocation. Gefitinib (GBTC) and pyrrolidine dithiocarbamate (PDTC) are capable of inhibiting EGFR/NOD2 and NF-kB, respectively. In earlier stages of dengue virus (DENV) infection, monocytes are capable of sustaining viral replication and increasing cytokine production, suggesting that monocyte/macrophages play an important role in early DENV replication. GBTC and PDTC have not been used to modify the pathogenesis of DENV in infected cells. This study was aimed to determine the effect of GBTC and PDTC on viral replication and cytokine production in DENV serotype 2 (DENV2)-infected human monocyte cultures. GBTC and PDTC were used to inhibit EGFR/NOD2 and NF-kB, respectively. Cytokine production was measured by ELISA and viral replication by plaque forming unit assay. Increased DENV2 replication and anti-viral cytokine production (IFN-α/β, TNF-α, IL-12 and IL-18) in infected cultures were found. These parameters were decreased after EGFR/NOD2 or NF-kB inhibitions. The inhibitory effects of GBTC and PDTC on viral replication and cytokine production can be beneficial in the treatment of patients infected by dengue and suggest a possible role of EGFR/NOD2 receptors and NF-kB in dengue pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Viral infections, prevalence and costs: A5-year, hospital based, retrospective observational study in shiraz, iran

    International Nuclear Information System (INIS)

    Sabayan, B.; Zamiri, N.; Chohedry, A.

    2007-01-01

    Many patients suffering from viral infections attend to health care centers. Data gathered from viral infections is limited to specific cases such as AIDS, viral hepatitis and Influenza. There is a significant lack of reliable documentation about other viral infections. In this study the prevalence and related costs of viral infections in hospitals of Shiraz University of Medical Sciences were reviewed. In this cross-sectional study the data were extracted from files of 1319 patients with viral infection admitted in two university hospitals during a five year period (1999-2004). The frequencies of different viral infections along with their demographic data were analyzed. The mean age of the patients was 29.24 with the range of 90 years. Hospitalization days were 8636 in 40 different wards in two hospitals. US$ 30.84 was the daily mean cost for each admitted patient. Viral meningitis was most frequent (14.2%) and 8.4% of patients died during hospitalization. This study confirms the necessity of expanding management programs for viral infections especially hepatitis B in youths in Iran. Unspecified viral infections cost much more than specified viral diseases. Viral infection costs can be reduced by finding more sensitive and specific diagnostic methods. (author)

  2. Early depletion of proliferating B cells of germinal center in rapidly progressive simian immunodeficiency virus infection

    International Nuclear Information System (INIS)

    Zhang Zhiqiang; Casimiro, Danilo R.; Schleif, William A.; Chen, Minchun; Citron, Michael; Davies, Mary-Ellen; Burns, Janine; Liang, Xiaoping; Fu, Tong-Ming; Handt, Larry; Emini, Emilio A.; Shiver, John W.

    2007-01-01

    Lack of virus specific antibody response is commonly observed in both HIV-1-infected humans and SIV-infected monkeys with rapid disease progression. However, the mechanisms underlying this important observation still remain unclear. In a titration study of a SIVmac239 viral stock, three out of six animals with viral inoculation rapidly progressed to AIDS within 5 months. Unexpectedly, there was no obvious depletion of CD4 + T cells in both peripheral and lymph node (LN) compartments in these animals. Instead, progressive depletion of proliferating B cells and disruption of the follicular dendritic cell (FDC) network in germinal centers (GC) was evident in the samples collected at as early as 20 days after viral challenge. This coincided with undetectable, or weak and transient, virus-specific antibody responses over the course of infection. In situ hybridization of SIV RNA in the LN samples revealed a high frequency of SIV productively infected cells and large amounts of accumulated viral RNA in the GCs in these animals. Early severe depletion of GC proliferating B cells and disruption of the FDC network may thus result in an inability to mount a virus-specific antibody response in rapid progressors, which has been shown to contribute to accelerated disease progression of SIV infection

  3. Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

    Energy Technology Data Exchange (ETDEWEB)

    Kohio, Hinissan P.; Adamson, Amy L., E-mail: aladamso@uncg.edu

    2013-09-15

    As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells.

  4. Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

    International Nuclear Information System (INIS)

    Kohio, Hinissan P.; Adamson, Amy L.

    2013-01-01

    As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells

  5. A method for quantifying mechanical properties of tissue following viral infection.

    Directory of Open Access Journals (Sweden)

    Vy Lam

    Full Text Available Viral infection and replication involves the reorganization of the actin network within the host cell. Actin plays a central role in the mechanical properties of cells. We have demonstrated a method to quantify changes in mechanical properties of fabricated model three-dimensional (3D connective tissue following viral infection. Using this method, we have characterized the impact of infection by the human herpesvirus, cytomegalovirus (HCMV. HCMV is a member of the herpesvirus family and infects a variety of cell types including fibroblasts. In the body, fibroblasts are necessary for maintaining connective tissue and function by creating mechanical force. Using this 3D connective tissue model, we observed that infection disrupted the cell's ability to generate force and reduced the cumulative contractile force of the tissue. The addition of HCMV viral particles in the absence of both viral gene expression and DNA replication was sufficient to disrupt tissue function. We observed that alterations of the mechanical properties are, in part, due to a disruption of the underlying complex actin microfilament network established by the embedded fibroblasts. Finally, we were able to prevent HCMV-mediated disruption of tissue function by the addition of human immune globulin against HCMV. This study demonstrates a method to quantify the impact of viral infection on mechanical properties which are not evident using conventional cell culture systems.

  6. CRISPR-Cas systems exploit viral DNA injection to establish and maintain adaptive immunity.

    Science.gov (United States)

    Modell, Joshua W; Jiang, Wenyan; Marraffini, Luciano A

    2017-04-06

    Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems provide protection against viral and plasmid infection by capturing short DNA sequences from these invaders and integrating them into the CRISPR locus of the prokaryotic host. These sequences, known as spacers, are transcribed into short CRISPR RNA guides that specify the cleavage site of Cas nucleases in the genome of the invader. It is not known when spacer sequences are acquired during viral infection. Here, to investigate this, we tracked spacer acquisition in Staphylococcus aureus cells harbouring a type II CRISPR-Cas9 system after infection with the staphylococcal bacteriophage ϕ12. We found that new spacers were acquired immediately after infection preferentially from the cos site, the viral free DNA end that is first injected into the cell. Analysis of spacer acquisition after infection with mutant phages demonstrated that most spacers are acquired during DNA injection, but not during other stages of the viral cycle that produce free DNA ends, such as DNA replication or packaging. Finally, we showed that spacers acquired from early-injected genomic regions, which direct Cas9 cleavage of the viral DNA immediately after infection, provide better immunity than spacers acquired from late-injected regions. Our results reveal that CRISPR-Cas systems exploit the phage life cycle to generate a pattern of spacer acquisition that ensures a successful CRISPR immune response.

  7. Early events associated with infection of Epstein-Barr virus infection of primary B-cells.

    Directory of Open Access Journals (Sweden)

    Sabyasachi Halder

    2009-09-01

    Full Text Available Epstein Barr virus (EBV is closely associated with the development of a vast number of human cancers. To develop a system for monitoring early cellular and viral events associated with EBV infection a self-recombining BAC containing 172-kb of the Epstein Barr virus genome BAC-EBV designated as MD1 BAC (Chen et al., 2005, J.Virology was used to introduce an expression cassette of green fluorescent protein (GFP by homologous recombination, and the resultant BAC clone, BAC-GFP-EBV was transfected into the HEK 293T epithelial cell line. The resulting recombinant GFP EBV was induced to produce progeny virus by chemical inducer from the stable HEK 293T BAC GFP EBV cell line and the virus was used to immortalize human primary B-cell as monitored by green fluorescence and outgrowth of the primary B cells. The infection, B-cell activation and cell proliferation due to GFP EBV was monitored by the expression of the B-cell surface antigens CD5, CD10, CD19, CD23, CD39, CD40 , CD44 and the intercellular proliferation marker Ki-67 using Flow cytometry. The results show a dramatic increase in Ki-67 which continues to increase by 6-7 days post-infection. Likewise, CD40 signals showed a gradual increase, whereas CD23 signals were increased by 6-12 hours, maximally by 3 days and then decreased. Monitoring the viral gene expression pattern showed an early burst of lytic gene expression. This up-regulation of lytic gene expression prior to latent genes during early infection strongly suggests that EBV infects primary B-cell with an initial burst of lytic gene expression and the resulting progeny virus is competent for infecting new primary B-cells. This process may be critical for establishment of latency prior to cellular transformation. The newly infected primary B-cells can be further analyzed for investigating B cell activation due to EBV infection.

  8. Discovery of Cellular Proteins Required for the Early Steps of HCV Infection Using Integrative Genomics

    Science.gov (United States)

    Yang, Jae-Seong; Kwon, Oh Sung; Kim, Sanguk; Jang, Sung Key

    2013-01-01

    Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets. PMID:23593195

  9. Cognitive function in early HIV infection.

    Science.gov (United States)

    Prakash, Aanchal; Hou, Jue; Liu, Lei; Gao, Yi; Kettering, Casey; Ragin, Ann B

    2017-04-01

    This study aimed to examine cognitive function in acute/early HIV infection over the subsequent 2 years. Fifty-six HIV+ subjects and 21 seronegative participants of the Chicago Early HIV Infection Study were evaluated using a comprehensive neuropsychological assessment at study enrollment and at 2-year follow-up. Cognitive performance measures were compared in the groups using t tests and mixed-effect models. Patterns of relationship with clinical measures were determined between cognitive function and clinical status markers using Spearman's correlations. At the initial timepoint, the HIV group demonstrated significantly weaker performance on measures of verbal memory, visual memory, psychomotor speed, motor speed, and executive function. A similar pattern was found when cognitive function was examined at follow-up and across both timepoints. The HIV subjects had generally weaker performance on psychomotor speed, executive function, motor speed, visual memory, and verbal memory. The rate of decline in cognitive function across the 2-year follow-up period did not differ between groups. Correlations between clinical status markers and cognitive function at both timepoints showed weaker performance associated with increased disease burden. Neurocognitive difficulty in chronic HIV infection may have very early onset and reflect consequences of initial brain viral invasion and neuroinflammation during the intense, uncontrolled viremia of acute HIV infection. Further characterization of the changes occurring in initial stages of infection and the risk and protective factors for cognitive function could inform new strategies for neuroprotection.

  10. Aptamers in Diagnostics and Treatment of Viral Infections

    Directory of Open Access Journals (Sweden)

    Tomasz Wandtke

    2015-02-01

    Full Text Available Aptamers are in vitro selected DNA or RNA molecules that are capable of binding a wide range of nucleic and non-nucleic acid molecules with high affinity and specificity. They have been conducted through the process known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment. It serves to reach specificity and considerable affinity to target molecules, including those of viral origin, both proteins and nucleic acids. Properties of aptamers allow detecting virus infected cells or viruses themselves and make them competitive to monoclonal antibodies. Specific aptamers can be used to interfere in each stage of the viral replication cycle and also inhibit its penetration into cells. Many current studies have reported possible application of aptamers as a treatment or diagnostic tool in viral infections, e.g., HIV (Human Immunodeficiency Virus, HBV (Hepatitis B Virus, HCV (Hepatitis C Virus, SARS (Severe Acute Respiratory Syndrome, H5N1 avian influenza and recently spread Ebola. This review presents current developments of using aptamers in the diagnostics and treatment of viral diseases.

  11. VIRAL ETIOLOGY OF RECURRENT URINARY TRACT INFECTIONS

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    H. S. Ibishev

    2017-01-01

    Full Text Available Introduction. Recurrent urinary tract infection is an actual problem of modern urology.Objective. Complex investigation of urinary tract infections including viral etiology for chronic recurrent cystitis in womenMaterials and methods. The study included 31 women with recurrent infection of urinary tract. Inclusion criteria were the presence of lower urinary tract symptoms caused by infection, severe recurrent course, the lack of anatomical and functional disorders of the urinary tract, the absence of bacterial pathogens during the study, taking into account the culture of aerobic and anaerobic culturing techniques.Results. The analysis of the clinical manifestations, the dominant in the study group were pain and urgency to urinate at 100% and 90% of women surveyed, respectively, and less frequent urination were recorded in 16.1% of patients. In general clinical examination of urine in all cases identified leukocyturia and 90% of the hematuria. By using a polymerase chain reaction (PCR in midstream urine of all examined was verified 10 types of human papilloma virus (HPV with the predominance of 16 and 18 types . Considering the presence of recurrent infectious and inflammatory processes of the urinary tract, cystoscopy with bladder biopsy was performed for all patients. When histomorphological biopsies of all patients surveyed noted the presence of the specific characteristics of HPV: papillary hyperplasia with squamous koilocytosis, pale cytoplasm and shrunken kernels. When analyzing the results of PCR biopsy data corresponded with the results of PCR in midstream urine in all biopsies was detected HPV.Conclusions. Human papillomavirus infection may be involved in the development of viral cystitis. In the etiological structure of viral cystitis, both highly oncogenic and low oncogenic HPV types can act.

  12. CD4 T Cell Responses in Latent and Chronic Viral Infections

    Science.gov (United States)

    Walton, Senta; Mandaric, Sanja; Oxenius, Annette

    2013-01-01

    The spectrum of tasks which is fulfilled by CD4 T cells in the setting of viral infections is large, ranging from support of CD8 T cells and humoral immunity to exertion of direct antiviral effector functions. While our knowledge about the differentiation pathways, plasticity, and memory of CD4 T cell responses upon acute infections or immunizations has significantly increased during the past years, much less is still known about CD4 T cell differentiation and their beneficial or pathological functions during persistent viral infections. In this review we summarize current knowledge about the differentiation, direct or indirect antiviral effector functions, and the regulation of virus-specific CD4 T cells in the setting of persistent latent or active chronic viral infections with a particular emphasis on herpes virus infections for the former and chronic lymphocytic choriomeningitis virus infection for the latter. PMID:23717308

  13. Translational Implication of Galectin-9 in the Pathogenesis and Treatment of Viral Infection

    Directory of Open Access Journals (Sweden)

    Jenn-Haung Lai

    2017-10-01

    Full Text Available The interaction between galectin-9 and its receptor, Tim-3, triggers a series of signaling events that regulate immune responses. The expression of galectin-9 has been shown to be increased in a variety of target cells of many different viruses, such as hepatitis C virus (HCV, hepatitis B virus (HBV, herpes simplex virus (HSV, influenza virus, dengue virus (DENV, and human immunodeficiency virus (HIV. This enhanced expression of galectin-9 following viral infection promotes significant changes in the behaviors of the virus-infected cells, and the resulting events tightly correlate with the immunopathogenesis of the viral disease. Because the human immune response to different viral infections can vary, and the lack of appropriate treatment can have potentially fatal consequences, understanding the implications of galectin-9 is crucial for developing better methods for monitoring and treating viral infections. This review seeks to address how we can apply the current understanding of galectin-9 function to better understand the pathogenesis of viral infection and better treat viral diseases.

  14. Acute viral infections of the central nervous system, 2014-2016, Greece.

    Science.gov (United States)

    Papa, Anna; Papadopoulou, Elpida

    2018-04-01

    In order to investigate the viral etiology of acute infections of central nervous system (CNS), multiplex and single PCRs combined with serology for arboviruses were applied on samples from 132 hospitalized patients in Greece during May 2014-December 2016. A viral pathogen was detected in 52 of 132 (39.4%) cases with acute CNS infection. Enteroviruses predominated (15/52, 28.8%), followed by West Nile virus (9/52, 17.3%). Phleboviruses, varicella-zoster virus, and Epstein-Barr virus accounted for 15.4%, 13.5%, and 11.5% of the cases, respectively. The study gives an insight into the etiology of viral CNS infections in a Mediterranean country, where arboviruses should be included in the differential diagnosis of acute CNS infections. © 2017 Wiley Periodicals, Inc.

  15. Impact of viral infections on urea and creatinine levels in patients ...

    African Journals Online (AJOL)

    Background: Chronic kidney disease (CKD) has emerged as a world-wide public health problem with substantial morbidity and mortality. Chronic viral infection is associated with a higher risk of death in patients with CKD undergoing haemodialysis. Objective: To evaluate the impact of viral infections on urea and creatinine ...

  16. The Incubation Period of Primary Epstein-Barr Virus Infection: Viral Dynamics and Immunologic Events.

    Directory of Open Access Journals (Sweden)

    Samantha K Dunmire

    2015-12-01

    Full Text Available Epstein-Barr virus (EBV is a human herpesvirus that causes acute infectious mononucleosis and is associated with cancer and autoimmune disease. While many studies have been performed examining acute disease in adults following primary infection, little is known about the virological and immunological events during EBV's lengthy 6 week incubation period owing to the challenge of collecting samples from this stage of infection. We conducted a prospective study in college students with special emphasis on frequent screening to capture blood and oral wash samples during the incubation period. Here we describe the viral dissemination and immune response in the 6 weeks prior to onset of acute infectious mononucleosis symptoms. While virus is presumed to be present in the oral cavity from time of transmission, we did not detect viral genomes in the oral wash until one week before symptom onset, at which time viral genomes were present in high copy numbers, suggesting loss of initial viral replication control. In contrast, using a sensitive nested PCR method, we detected viral genomes at low levels in blood about 3 weeks before symptoms. However, high levels of EBV in the blood were only observed close to symptom onset-coincident with or just after increased viral detection in the oral cavity. These data imply that B cells are the major reservoir of virus in the oral cavity prior to infectious mononucleosis. The early presence of viral genomes in the blood, even at low levels, correlated with a striking decrease in the number of circulating plasmacytoid dendritic cells well before symptom onset, which remained depressed throughout convalescence. On the other hand, natural killer cells expanded only after symptom onset. Likewise, CD4+ Foxp3+ regulatory T cells decreased two fold, but only after symptom onset. We observed no substantial virus specific CD8 T cell expansion during the incubation period, although polyclonal CD8 activation was detected in

  17. Transfusions of blood and blood products and viral infections

    Directory of Open Access Journals (Sweden)

    Marta Wróblewska

    2002-06-01

    Full Text Available Transfusions of blood and blood products are commonly used in medicine, but being biological materials they carry a risk of transmitting infections--viral, bacterial, parasitic, as well as prions. Laboratory tests used for screening of donated blood for viral infections at present cannot detect all infectious units. Criteria for selection of blood donors therefore must be very strict, while methods of inactivation of viruses and laboratory assays for detection of their presence must be improved. Indications for blood transfusion should be restricted.

  18. Early-life exposure to outdoor air pollution and respiratory health, ear infections, and eczema in infants from the INMA study

    DEFF Research Database (Denmark)

    Aguilera, Inmaculada; Pedersen, Marie; Garcia-Esteban, Raquel

    2013-01-01

    the first 12-18 months of age in a Spanish birth cohort of 2,199 infants. METHODS: We obtained parentally reported information on doctor-diagnosed lower respiratory tract infections (LRTI) and parental reports of wheezing, eczema, and ear infections. We estimated individual exposures to nitrogen dioxide (NO...... and lower respiratory tract infections in infants.......BACKGROUND: Prenatal and early-life periods may be critical windows for harmful effects of air pollution on infant health. OBJECTIVES: We studied the association of air pollution exposure during pregnancy and the first year of life with respiratory illnesses, ear infections, and eczema during...

  19. Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction

    Science.gov (United States)

    Cyr, Derek D.; Lucas, Joseph E.; Zaas, Aimee K.; Woods, Christopher W.; Newby, L. Kristin; Kraus, William E.; Ginsburg, Geoffrey S.

    2015-01-01

    Background Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI. Methods A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status. Results In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2% (69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04). Conclusions A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection

  20. A systematic review of viral infections associated with oral involvement in cancer patients : a spotlight on Herpesviridea

    NARCIS (Netherlands)

    Elad, Sharon; Zadik, Yehuda; Hewson, Ian; Hovan, Allan; Correa, M. Elvira P.; Logan, Richard; Elting, Linda S.; Spijkervet, Fred K. L.; Brennan, Michael T.

    Our aim was to evaluate the literature for the prevalence of and interventions for oral viral infections and, based on scientific evidence, point to effective treatment protocols. Quality of life (QOL) and economic impact were assessed if available in the articles reviewed. Our search of the English

  1. INFLUENZA AND ACUTE VIRAL RESPIRATORY INFECTIONS IN THE PRACTICE OF THE EMERGENCY CREWS OF MOSCOW

    Directory of Open Access Journals (Sweden)

    N. F. Plavunov

    2016-01-01

    Full Text Available Influenza and acute viral respiratory infections have a great social significance during epidemic rise of morbidity and demand differential diagnosis of pneumonia with bacterial etiology and consultation with an infectious disease doctor in case of seeing patients in non-core hospitals. This article highlights the problem of influenza and acute respiratory viral infections’ early diagnosis. Clinical manifestations of influenza and other respiratory extremely similar. The differential diagnosis must take into account the presence of mixed infection in the same patient. According to the results of consultative infectious ambulance teams in 2014-2016, quality of diagnostics of this infectious pathology was examined. Observed deaths in persons later seeking medical treatment, not receiving timely antiviral therapy and related to high-risk groups: patients with obesity, chronic alcohol intoxication, diabetes, pregnant women. Influenza and acute viral respiratory infections, more complicated by pneumonia, people in the older age group, indicating the need for timely medical evacuation of patients older than 60 years. In some cases, in the diagnosis of influenza was helped by the results of laboratory studies (especially the trend to leukopenia and a positive rapid test. It should be noted that a negative rapid test for influenza was not a reason for exclusion of the diagnosis “influenza”.

  2. Dynamics of CD4 Lymphocytes and Viral Load at the Natural History of Perinatal HIV-infection

    Directory of Open Access Journals (Sweden)

    T. A. Daminov

    2015-01-01

    Full Text Available This article presents the analysis of indicators of CD4 lymphocyte count and viral load in the natural history (in the absence of ART in perinatally HIV-infected children. It was revealed that perinatal way of transmission is characterized by a higher rate of immunodeficiency progression. It may be associated with intrauterine infection, as well as an early defeat HIV immature immune system of the child. The concentration of virus in perinatally infected children since the beginning of the observation and in 30 months after infection is more than in parenterally infected children in 5 and 2 times, respectively, which determines a infavourable version of the disease in perinatally infected children.

  3. DMPD: Toll-like receptors regulation of viral infection and disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18280610 Toll-like receptors regulation of viral infection and disease. Thompson JM...how Toll-like receptors regulation of viral infection and disease. PubmedID 18280610 Title Toll-like recepto...rs regulation of viral infection and disease. Authors Thompson JM, Iwasaki A. Pub

  4. The Canonical Immediate Early 3 Gene Product pIE611 of Mouse Cytomegalovirus Is Dispensable for Viral Replication but Mediates Transcriptional and Posttranscriptional Regulation of Viral Gene Products.

    Science.gov (United States)

    Rattay, Stephanie; Trilling, Mirko; Megger, Dominik A; Sitek, Barbara; Meyer, Helmut E; Hengel, Hartmut; Le-Trilling, Vu Thuy Khanh

    2015-08-01

    Transcription of mouse cytomegalovirus (MCMV) immediate early ie1 and ie3 is controlled by the major immediate early promoter/enhancer (MIEP) and requires differential splicing. Based on complete loss of genome replication of an MCMV mutant carrying a deletion of the ie3-specific exon 5, the multifunctional IE3 protein (611 amino acids; pIE611) is considered essential for viral replication. Our analysis of ie3 transcription resulted in the identification of novel ie3 isoforms derived from alternatively spliced ie3 transcripts. Construction of an IE3-hemagglutinin (IE3-HA) virus by insertion of an in-frame HA epitope sequence allowed detection of the IE3 isoforms in infected cells, verifying that the newly identified transcripts code for proteins. This prompted the construction of an MCMV mutant lacking ie611 but retaining the coding capacity for the newly identified isoforms ie453 and ie310. Using Δie611 MCMV, we demonstrated the dispensability of the canonical ie3 gene product pIE611 for viral replication. To determine the role of pIE611 for viral gene expression during MCMV infection in an unbiased global approach, we used label-free quantitative mass spectrometry to delineate pIE611-dependent changes of the MCMV proteome. Interestingly, further analysis revealed transcriptional as well as posttranscriptional regulation of MCMV gene products by pIE611. Cytomegaloviruses are pathogenic betaherpesviruses persisting in a lifelong latency from which reactivation can occur under conditions of immunosuppression, immunoimmaturity, or inflammation. The switch from latency to reactivation requires expression of immediate early genes. Therefore, understanding of immediate early gene regulation might add insights into viral pathogenesis. The mouse cytomegalovirus (MCMV) immediate early 3 protein (611 amino acids; pIE611) is considered essential for viral replication. The identification of novel protein isoforms derived from alternatively spliced ie3 transcripts prompted

  5. Early life traumatic stressors and the mediating role of PTSD in incident HIV infection among US men, comparisons by sexual orientation and race/ethnicity: results from the NESARC, 2004-2005.

    Science.gov (United States)

    Reisner, Sari L; Falb, Kathryn L; Mimiaga, Matthew J

    2011-08-01

    Stressful life events in childhood during critical periods of development have long-term psychological and neurobiological sequelae, which may affect risk for HIV infection across the life course. Data were from a nationally representative sample of 13,274 US men (National Epidemiologic Survey on Alcohol and Related Conditions, 2004-2005). Weighted multivariable logistic regression models examined (1) the association of childhood violent events before age 18 on 12-month incident HIV infection and (2) whether posttraumatic stress disorder (PTSD) diagnosis (clinical interview) mediated the association between early life events and HIV. Overall, the 12-month HIV incidence was incident HIV infection (aOR = 5.75; 95% CI: 4.76 to 6.95). There was evidence that PTSD partially mediated the relationship between early life events and HIV (aOR = 1.14; 95% CI: 1.02 to 1.28). Experiencing early life violent family stressors was associated with HIV infection among men. Early life events and HIV infection were mediated by PTSD, which has implications for understanding disparities in HIV infection. Interventions are urgently needed that address the long-term sequelae of childhood violence.

  6. Budesonide and formoterol reduce early innate anti-viral immune responses in vitro.

    Directory of Open Access Journals (Sweden)

    Janet M Davies

    Full Text Available Asthma is a chronic inflammatory airways disease in which respiratory viral infections frequently trigger exacerbations. Current treatment of asthma with combinations of inhaled corticosteroids and long acting beta2 agonists improves asthma control and reduces exacerbations but what impact this might have on innate anti-viral immunity is unclear. We investigated the in vitro effects of asthma drugs on innate anti-viral immunity. Peripheral blood mononuclear cells (PBMC from healthy and asthmatic donors were cultured for 24 hours with the Toll-like receptor 7 agonist, imiquimod, or rhinovirus 16 (RV16 in the presence of budesonide and/or formoterol. Production of proinflammatory cytokines and expression of anti-viral intracellular signalling molecules were measured by ELISA and RT-PCR respectively. In PBMC from healthy donors, budesonide alone inhibited IP-10 and IL-6 production induced by imiquimod in a concentration-dependent manner and the degree of inhibition was amplified when budesonide and formoterol were used in combination. Formoterol alone had little effect on these parameters, except at high concentrations (10⁻⁶ M when IL-6 production increased. In RV16 stimulated PBMC, the combination of budesonide and formoterol inhibited IFNα and IP-10 production in asthmatic as well as healthy donors. Combination of budesonide and formoterol also inhibited RV16-stimulated expression of the type I IFN induced genes myxovirus protein A and 2', 5' oligoadenylate synthetise. Notably, RV16 stimulated lower levels of type Myxovirus A and oligoadenylate synthase in PBMC of asthmatics than control donors. These in vitro studies demonstrate that combinations of drugs commonly used in asthma therapy inhibit both early pro-inflammatory cytokines and key aspects of the type I IFN pathway. These findings suggest that budesonide and formoterol curtail excessive inflammation induced by rhinovirus infections in patients with asthma, but whether this inhibits

  7. FEVER AS INDICATOR TO SECONDARY INFECTION IN DENGUE VIRAL INFECTION

    Directory of Open Access Journals (Sweden)

    Soegeng Soegijanto

    2018-04-01

    Full Text Available Dengue Virus Infections are distributed in tropical and sub-tropical regions and transmitted by the mosquitoes such as Aedes aegypti and Aedes albopictus. Dengue virus can cause dengue fever, dengue hemorrhagic fever and dengue shock syndrome or dengue and severe dengue classified by World Health Organization. Beside it concurrent infection virus salmonella had been found some cases who showed fever more than 7 days. Concurrent infection with two agents can result in an illness having overlapping symptoms creating a diagnostic dilemma for treating physician, such as dengue fever with typhoid fever. The aim of this research is detection of dengue virus and secondary infection with Salmonella typhi in patients suspected dengue virus infection. Detection of dengue virus and Salmonella typhi using immunochromatography test such as NS1, IgG/IgM for dengue virus infection, and IgM/IgG Salmonella and blood culture. The fifty children with dengue virus infection came to Soerya hospital and 17 cases suspected dengue virus infection, five cases showed a positive NS1 on the second day of fever and one case concurrent with clinical manifestation of convulsi on the third days of fever there were five cases only showed positive. It was showed in this study that on the fourth to six day of fever in dengue virus infection accompanied by antibody IgM & IgG dengue. There were 12 cases showed the clinical manifestation of concurrent dengue viral infection and Salmonella, all of them showed a mild clinical manifestation and did not show plasma leakage and shock. In this study we found the length of stay of concurrent Dengue Virus Infection and Salmonella infection is more than 10 days. These patients were also more likely to have co-existing haemodynamic disturbances and bacterial septicaemia which would have required treatment with inotropes and antibiotics. This idea is very important to make update dengue viral management to decrease mortality in outbreak try to

  8. Viral MicroRNAs Repress the Cholesterol Pathway, and 25-Hydroxycholesterol Inhibits Infection.

    Science.gov (United States)

    Serquiña, Anna K P; Kambach, Diane M; Sarker, Ontara; Ziegelbauer, Joseph M

    2017-07-11

    From various screens, we found that Kaposi's sarcoma-associated herpesvirus (KSHV) viral microRNAs (miRNAs) target several enzymes in the mevalonate/cholesterol pathway. 3-Hydroxy-3-methylglutaryl-coenzyme A (CoA) synthase 1 (HMGCS1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR [a rate-limiting step in the mevalonate pathway]), and farnesyl-diphosphate farnesyltransferase 1 (FDFT1 [a committed step in the cholesterol branch]) are repressed by multiple KSHV miRNAs. Transfection of viral miRNA mimics in primary endothelial cells (human umbilical vein endothelial cells [HUVECs]) is sufficient to reduce intracellular cholesterol levels; however, small interfering RNAs (siRNAs) targeting only HMGCS1 did not reduce cholesterol levels. This suggests that multiple targets are needed to perturb this tightly regulated pathway. We also report here that cholesterol levels were decreased in de novo -infected HUVECs after 7 days. This reduction is at least partially due to viral miRNAs, since the mutant form of KSHV lacking 10 of the 12 miRNA genes had increased cholesterol compared to wild-type infections. We hypothesized that KSHV is downregulating cholesterol to suppress the antiviral response by a modified form of cholesterol, 25-hydroxycholesterol (25HC). We found that the cholesterol 25-hydroxylase (CH25H) gene, which is responsible for generating 25HC, had increased expression in de novo -infected HUVECs but was strongly suppressed in long-term latently infected cell lines. We found that 25HC inhibits KSHV infection when added exogenously prior to de novo infection. In conclusion, we found that multiple KSHV viral miRNAs target enzymes in the mevalonate pathway to modulate cholesterol in infected cells during latency. This repression of cholesterol levels could potentially be beneficial to viral infection by decreasing the levels of 25HC. IMPORTANCE A subset of viruses express unique microRNAs (miRNAs), which act like cellular miRNAs to generally repress host gene

  9. A review of hepatitis viral infections in Pakistan

    International Nuclear Information System (INIS)

    Bosan, A.; Qureshi, H.; Bile, K.M.; Ahmad, I.; Hafiz, R.

    2010-01-01

    A review of published literature on viral hepatitis infections in Pakistan is presented. A total of 220 abstracts available in the Pakmedinet and Medline have been searched. All relevant articles were reviewed to determine the prevalence of hepatitis viral infections in Pakistan. Two hundred and three (203) relevant articles/abstracts including twenty nine supporting references are included in this review. Of the articles on prevalence of hepatitis infection, seven were related to Hepatitis A, fifteen to Hepatitis E while the remaining articles were on frequency of hepatitis B and C in different disease and healthy population groups. These included eight studies on healthy children, three on vertical transmission, nineteen on pregnant women, fifteen on healthy individuals, six on army recruits, thirty one on blood donors, thirteen on health care workers, five on unsafe injections, seventeen on high risk groups, five on patients with provisional diagnosis of hepatitis, thirty three on patients with chronic liver disease, four on genotypes of HBV and five on genotypes of HCV. This review highlights the lack of community-based epidemiological work as the number of subjects studied were predominantly patients, high risk groups and healthy blood donors. High level of Hepatitis A seroconversion was found in children and this viral infection accounts for almost 50%- 60% of all cases of acute viral hepatitis in children in Pakistan. Hepatitis E is endemic in the country affecting mostly the adult population and epidemic situations have been reported from many parts of the country. The mean results of HBsAg and Anti-HCV prevalence on the basis of data aggregated from several studies was calculated which shows 2.3% and 2.5% prevalence of HBsAg and Anti-HCV in children, 2.5% and 5.2% among pregnant women, 2.6% and 5.3% in general population, 3.5% and 3.1% in army recruits, 2.4% and 3.6% in blood donors, 6.0% and 5.4% in health care workers, 13.0% and 10.3% in high risk groups

  10. Interferon-inducible protein 10 (IP-10) is associated with viremia of early HIV-1 infection in Korean patients.

    Science.gov (United States)

    Lee, SoYong; Chung, Yoon-Seok; Yoon, Cheol-Hee; Shin, YoungHyun; Kim, SeungHyun; Choi, Byeong-Sun; Kim, Sung Soon

    2015-05-01

    Cytokines/chemokines play key roles in modulating disease progression in human immunodeficiency virus (HIV) infection. Although it is known that early HIV-1 infection is associated with increased production of proinflammatory cytokines, the relationship between cytokine levels and HIV-1 pathogenesis is not clear. The concentrations of 18 cytokines/chemokines in 30 HIV-1 negative and 208 HIV-1 positive plasma samples from Korean patients were measured by the Luminex system. Early HIV-1 infection was classified according to the Fiebig stage (FS) based on the characteristics of the patients infected with HIV-1. Concentrations of interleukin-12 (IL-12), interferon-inducible protein-10 (IP-10), macrophage inflammatory protein-1α (MIP-1α) and regulated upon activation, normal T cells expressed and secreted (RANTES) were increased significantly during the early stage of HIV-1 infection (FS II-IV) compared with the HIV-1-negative group. Of these cytokines, an elevated level of IP-10 was the only factor to be correlated positively with a higher viral load during the early stages of HIV-1 infection (FS II-IV) in Koreans (R = 0.52, P IP-10 may be an indicator for HIV-1 viremia and associated closely with viral replication in patients with early HIV-1 infection. © 2015 Wiley Periodicals, Inc.

  11. Compartmentalization of the gut viral reservoir in HIV-1 infected patients

    Directory of Open Access Journals (Sweden)

    Grant Tannika

    2007-12-01

    Full Text Available Abstract Background Recently there has been an increasing interest and appreciation for the gut as both a viral reservoir as well as an important host-pathogen interface in human immunodefiency virus type 1 (HIV-1 infection. The gut associated lymphoid tissue (GALT is the largest lymphoid organ infected by HIV-1. In this study we examined if different HIV-1 quasispecies are found in different parts of the gut of HIV-1 infected individuals. Results Gut biopsies (esophagus, stomach, duodenum and colorectum were obtained from eight HIV-1 infected preHAART (highly active antiretroviral therapy patients. HIV-1 Nef and Reverse transcriptase (RT encoding sequences were obtained through nested PCR amplification from DNA isolated from the gut biopsy tissues. The PCR fragments were cloned and sequenced. The resulting sequences were subjected to various phylogenetic analyses. Expression of the nef gene and viral RNA in the different gut tissues was determined using real-time RT-PCR. Phylogenetic analysis of the Nef protein-encoding region revealed compartmentalization of viral replication in the gut within patients. Viral diversity in both the Nef and RT encoding region varied in different parts of the gut. Moreover, increased nef gene expression (p Conclusion Our results indicated that different HIV-1 quasispecies populate different parts of the gut, and that viral replication in the gut is compartmentalized. These observations underscore the importance of the gut as a host-pathogen interface in HIV-1 infection.

  12. Early life insults as determinants of chronic obstructive pulmonary disease in adult life

    DEFF Research Database (Denmark)

    Savran, Osman; Ulrik, Charlotte Suppli

    2018-01-01

    Background: Early life events may predispose to the development of chronic lung disease in adulthood. Aim: To provide an update on current knowledge of early nongenetic origins of COPD. Materials and methods: Systematic literature review was performed according to the Preferred Reporting Items...... in utero and early life is a risk factor for subsequent development of COPD. Furthermore, low birth weight, lower respiratory tract infections and asthma, including wheezy bronchitis, in childhood also seem to be important determinants for later development of COPD. Early life insults may, therefore...

  13. Respiratory viral infections in infants with clinically suspected pertussis

    Directory of Open Access Journals (Sweden)

    Angela E. Ferronato

    2013-11-01

    Conclusion: the results suggest that viral infection can be present in hospitalized infants with clinical suspicion of pertussis, and etiological tests may enable a reduction in the use of macrolides in some cases. However, the etiological diagnosis of respiratory virus infection, by itself, does not exclude the possibility of infection with BP.

  14. Patterns of viral infection in honey bee queens

    DEFF Research Database (Denmark)

    Francis, Roy Mathew; Kryger, Per; Nielsen, Steen Lykke

    2013-01-01

    by two real-time PCRs: one for the presence of deformed wing virus (DWV), and one that would detect sequences of acute bee-paralysis virus, Kashmir bee virus and Israeli acute paralysis virus (AKI complex). Worker bees accompanying the queen were also analysed. The queens could be divided into three......The well-being of a colony and replenishment of the workers depends on a healthy queen. Diseases in queens are seldom reported, and our knowledge on viral infection in queens is limited. In this study, 86 honey bee queens were collected from beekeepers in Denmark. All queens were tested separately...... groups based on the level of infection in their head, thorax, ovary, intestines and spermatheca. Four queens exhibited egg-laying deficiency, but visually all queens appeared healthy. Viral infection was generally at a low level in terms of AKI copy numbers, with 134/430 tissues (31 %) showing...

  15. Interferon therapy of acute respiratory viral infections in children

    Directory of Open Access Journals (Sweden)

    A.E. Abaturov

    2017-04-01

    Full Text Available The purpose of our study was to evaluate the efficacy and tolerability of nasal spray Laferobionum® (100,000 IU/ml in children with acute respiratory viral infections. Materials and methods. The study included 84 children aged 12 to 18 years. Children of the main group (42 persons received Laferobionum® spray in addition to the standard treatment for acute respiratory viral infections. The drug was administered to children of 12–14 years for 2 spray doses in each nasal passage 4–5 times a day at regular intervals (with the exception of sleep time, children aged 14–18 years received 3 spray-doses per each nasal passage 5–6 times a day at regular intervals (excluding sleep time. The course of treatment for all subjects was 5 days. Children of the control group received standard treatment for acute respiratory viral infections without Laferobionum®. Objective research included: auscultation of the heart and lungs, examination of the skin and mucous membranes, measurement of heart rate, blood pressure and body temperature. All patients underwent a general blood test, a general urinalysis, identification of the pathogen using the method of direct immunofluorescence (in smears taken from the nasal passages in the laboratory “Medical Diagnostic Center of Dnipropetrovsk Medical Academy”. Results. In the non-epidemic period, the respiratory syncytial virus and adenoviruses were the leading viral pathogens of acute respiratory viral infections. The main clinical manifestations of acute respiratory viral infection in the observed patients were signs of general inflammatory and catarrhal syndromes. All patients had not severe course of the disease. The data of the physical examination performed before the beginning of treatment indicated the absence of clinically significant deviations from the cardiovascular system in the children of the main and control groups. Arterial blood pressure and heart rate in the subjects of both groups were

  16. Productive infection of human immunodeficiency virus type 1 in dendritic cells requires fusion-mediated viral entry

    International Nuclear Information System (INIS)

    Janas, Alicia M.; Dong, Chunsheng; Wang Jianhua; Wu Li

    2008-01-01

    Human immunodeficiency virus type 1 (HIV-1) enters dendritic cells (DCs) through endocytosis and viral receptor-mediated fusion. Although endocytosis-mediated HIV-1 entry can generate productive infection in certain cell types, including human monocyte-derived macrophages, productive HIV-1 infection in DCs appears to be dependent on fusion-mediated viral entry. It remains to be defined whether endocytosed HIV-1 in DCs can initiate productive infection. Using HIV-1 infection and cellular fractionation assays to measure productive viral infection and entry, here we show that HIV-1 enters monocyte-derived DCs predominately through endocytosis; however, endocytosed HIV-1 cannot initiate productive HIV-1 infection in DCs. In contrast, productive HIV-1 infection in DCs requires fusion-mediated viral entry. Together, these results provide functional evidence in understanding HIV-1 cis-infection of DCs, suggesting that different pathways of HIV-1 entry into DCs determine the outcome of viral infection

  17. Emerging infectious diseases with cutaneous manifestations: Viral and bacterial infections.

    Science.gov (United States)

    Nawas, Zeena Y; Tong, Yun; Kollipara, Ramya; Peranteau, Andrew J; Woc-Colburn, Laila; Yan, Albert C; Lupi, Omar; Tyring, Stephen K

    2016-07-01

    Given increased international travel, immigration, and climate change, bacterial and viral infections that were once unrecognized or uncommon are being seen more frequently in the Western Hemisphere. A delay in diagnosis and treatment of these diseases can lead to significant patient morbidity and mortality. However, the diagnosis and management of these infections is fraught with a lack of consistency because there is a dearth of dermatology literature on the cutaneous manifestations of these infections. We review the epidemiology, cutaneous manifestations, diagnosis, and management of these emerging bacterial and viral diseases. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  18. Antibody maturation and viral diversification in HIV-infected women.

    Directory of Open Access Journals (Sweden)

    Maria M James

    Full Text Available The Post-exposure Prophylaxis in Infants (PEPI-Malawi trial evaluated infant antiretroviral regimens for prevention of post-natal HIV transmission. A multi-assay algorithm (MAA that includes the BED capture immunoassay, an avidity assay, CD4 cell count, and viral load was used to identify women who were vs. were not recently infected at the time of enrollment (MAA recent, N = 73; MAA non-recent, N = 2,488; a subset of the women in the MAA non-recent group known to have been HIV infected for at least 2 years before enrollment (known non-recent, N = 54. Antibody maturation and viral diversification were examined in these women.Samples collected at enrollment (N = 2,561 and 12-24 months later (N = 1,306 were available for serologic analysis using the BED and avidity assays. A subset of those samples was used for analysis of viral diversity, which was performed using a high resolution melting (HRM diversity assay. Viral diversity analysis was performed using all available samples from women in the MAA recent group (61 enrollment samples, 38 follow-up samples and the known non-recent group (43 enrollment samples, 22 follow-up samples. Diversity data from PEPI-Malawi were also compared to similar data from 169 adults in the United States (US with known recent infection (N = 102 and known non-recent infection (N = 67.In PEPI-Malawi, results from the BED and avidity assays increased over time in the MAA recent group, but did not change significantly in the MAA non-recent group. At enrollment, HIV diversity was lower in the MAA recent group than in the known non-recent group. HRM diversity assay results from women in PEPI-Malawi were similar to those from adults in the US with known duration of HIV infection.Antibody maturation and HIV diversification patterns in African women provide additional support for use of the MAA to identify populations with recent HIV infection.

  19. T Cell Immunosenescence after Early Life Adversity: Association with Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Martha M. C. Elwenspoek

    2017-10-01

    Full Text Available Early life adversity (ELA increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences. However, it is unclear what drives ELA-associated immunosenescence and which cells are primarily affected. We investigated different biomarkers of immunosenescence in a healthy subset of the EpiPath cohort. Participants were either parent-reared (Ctrl, n = 59 or had experienced separation from their parents in early childhood and were subsequently adopted (ELA, n = 18. No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood, containing a heterogeneous mixture of immune cells. However, when specifically investigating T cells, we found a higher expression of senescence markers (CD57 in ELA. In addition, senescent T cells (CD57+ in ELA had an increased cytolytic potential compared to senescent cells in controls. With a mediation analysis we demonstrated that cytomegalovirus (CMV infection, which is an important driving force of immunosenescence, largely accounted for elevated CD57 expression observed in ELA. Leukocyte telomere length may obscure cell-specific immunosenescence; here, we demonstrated that the use of cell surface markers of senescence can be more informative. Our data suggest that ELA may increase the risk of CMV infection in early childhood, thereby mediating the effect of ELA on T cell-specific immunosenescence. Thus, future studies should include CMV as a confounder or selectively investigate CMV seronegative cohorts.

  20. Acute hepatitis A virus infection is associated with a limited type I interferon response and persistence of intrahepatic viral RNA.

    Science.gov (United States)

    Lanford, Robert E; Feng, Zongdi; Chavez, Deborah; Guerra, Bernadette; Brasky, Kathleen M; Zhou, Yan; Yamane, Daisuke; Perelson, Alan S; Walker, Christopher M; Lemon, Stanley M

    2011-07-05

    Hepatitis A virus (HAV) is an hepatotropic human picornavirus that is associated only with acute infection. Its pathogenesis is not well understood because there are few studies in animal models using modern methodologies. We characterized HAV infections in three chimpanzees, quantifying viral RNA by quantitative RT-PCR and examining critical aspects of the innate immune response including intrahepatic IFN-stimulated gene expression. We compared these infection profiles with similar studies of chimpanzees infected with hepatitis C virus (HCV), an hepatotropic flavivirus that frequently causes persistent infection. Surprisingly, HAV-infected animals exhibited very limited induction of type I IFN-stimulated genes in the liver compared with chimpanzees with acute resolving HCV infection, despite similar levels of viremia and 100-fold greater quantities of viral RNA in the liver. Minimal IFN-stimulated gene 15 and IFIT1 responses peaked 1-2 wk after HAV challenge and then subsided despite continuing high hepatic viral RNA. An acute inflammatory response at 3-4 wk correlated with the appearance of virus-specific antibodies and apoptosis and proliferation of hepatocytes. Despite this, HAV RNA persisted in the liver for months, remaining present long after clearance from serum and feces and revealing dramatic differences in the kinetics of clearance in the three compartments. Viral RNA was detected in the liver for significantly longer (35 to >48 wk) than HCV RNA in animals with acute resolving HCV infection (10-20 wk). Collectively, these findings indicate that HAV is far stealthier than HCV early in the course of acute resolving infection. HAV infections represent a distinctly different paradigm in virus-host interactions within the liver.

  1. DNA cleavage enzymes for treatment of persistent viral infections: Recent advances and the pathway forward

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Nicholas D., E-mail: nweber@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Department of Laboratory Medicine, University of Washington, Seattle, WA 98195 (United States); Aubert, Martine, E-mail: maubert@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Dang, Chung H., E-mail: cdang@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Stone, Daniel, E-mail: dstone2@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Jerome, Keith R., E-mail: kjerome@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Department of Laboratory Medicine, University of Washington, Seattle, WA 98195 (United States); Department of Microbiology, University of Washington, Seattle, WA 98195 (United States)

    2014-04-15

    Treatment for most persistent viral infections consists of palliative drug options rather than curative approaches. This is often because long-lasting viral DNA in infected cells is not affected by current antivirals, providing a source for viral persistence and reactivation. Targeting latent viral DNA itself could therefore provide a basis for novel curative strategies. DNA cleavage enzymes can be used to induce targeted mutagenesis of specific genes, including those of exogenous viruses. Although initial in vitro and even in vivo studies have been carried out using DNA cleavage enzymes targeting various viruses, many questions still remain concerning the feasibility of these strategies as they transition into preclinical research. Here, we review the most recent findings on DNA cleavage enzymes for human viral infections, consider the most relevant animal models for several human viral infections, and address issues regarding safety and enzyme delivery. Results from well-designed in vivo studies will ideally provide answers to the most urgent remaining questions, and allow continued progress toward clinical application. - Highlights: • Recent in vitro and in vivo results for DNA cleavage enzymes targeting persistent viral infections. • Analysis of the best animal models for testing enzymes for HBV, HSV, HIV and HPV. • Challenges facing in vivo delivery of therapeutic enzymes for persistent viral infections. • Safety issues to be addressed with proper animal studies.

  2. [Prevalence and risk factors of respiratory viral infection in acute exacerbation of chronic obstructive pulmonary disease].

    Science.gov (United States)

    Du, X B; Ma, X; Gao, Y; Wen, L F; Li, J; Wang, Z Z; Liu, S

    2017-04-12

    Objective: To study the prevalence of respiratory viral infection in chronic obstructive pulmonary disease(COPD) exacerbations and to find the factors associated with susceptibility to viral infections. Methods: Eighty patients with exacerbations of COPD and 50 stable COPD patients were recruited. Nasopharyngeal swabs were tested for a range of 18 different respiratory viruses using PCR. Results: Among the COPD exacerbations, viral infection was detected in 18 episodes (22.5%) . The most common virus was rhinovirus (33.3%), followed by coronavirus(27.8%), parainfluenza(22.2%), metapneumovirus(11.1%) and influenza virus B(5.6%). The prevalence of viral infection was 8% in the stable COPD patients. In multivariate regression analysis fever was found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 4.99, 95% CI 1.51-16.48, P =0.008). Conclusion: Viral respiratory pathogens were more often detected in respiratory specimens from hospitalized patients with AECOPD than those with stable COPD. Rhinovirus was the most common infecting agent identified. The symptom of fever was associated with viral detection.

  3. Clinical definition of respiratory viral infections in young children and potential bronchiolitis misclassification.

    Science.gov (United States)

    Megalaa, Rosemary; Perez, Geovanny F; Kilaikode-Cheruveettara, Sasikumar; Kotwal, Nidhi; Rodriguez-Martinez, Carlos E; Nino, Gustavo

    2018-01-01

    Viral respiratory infections are often grouped as a single respiratory syndrome named 'viral bronchiolitis', independently of the viral etiology or individual risk factors. Clinical trials and guidelines have used a more stringent definition of viral bronchiolitis, including only the first episode of wheezing in children less than 12 months of age without concomitant respiratory comorbidities. There is increasing evidence suggesting that this definition is not being followed by pediatric care providers, but it is unclear to what extent viral respiratory infections are currently misclassified as viral bronchiolitis using standard definitions. We conducted a retrospective analysis of hospitalized young children (≤3 years) due to viral respiratory infections. Bronchiolitis was defined as the first wheezing episode less than 12 months of age. Demographic variables and comorbidities were obtained by electronic medical record review. The study comprised a total of 513 hospitalizations (n=453). Viral bronchiolitis was diagnosed in 144 admissions (28.1%). Notably, we identified that the majority of children diagnosed with bronchiolitis (63%) were misclassified as they had prior episodes of wheezing. Many children with bronchiolitis misclassification had significant comorbidities, including prematurity (51%), neuromuscular conditions (9.8%), and congenital heart disease (9.8%). Misclassification of bronchiolitis is a common problem that may lead to inappropriate management of viral respiratory infections in young children. A comprehensive approach that takes into consideration viral etiology and individual risk factors may lead to a more accurate clinical assessment of this condition and would potentially prevent bronchiolitis misclassification. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. MODERN APPROACHES TO THE THERAPY OF VIRAL PAPILLOMA SKIN INFECTION IN INFANCY

    Directory of Open Access Journals (Sweden)

    L.K. Aslamazian

    2006-01-01

    Full Text Available To improve the methods of prevention and treatment of viral papilloma infection, the researchers examined 80 children, suffering from skin forms of a disease. They examined peculiarities of a disease and interferon status of all the children. The data of clinic and laboratory research allowed them to assume that viral papilloma infection grows along with the reduction of immune mechanisms and it grows among the children, suffering from the genetic burden to viral diseases. All the patients, suffering from the disorder of interferon status, have undergone the complex therapy, which included medications of recombinant interferon (Viferon in suppositories and extrinsic. For the first time, the researchers removed the skin papillomas by a combination method: cryofreezing and photovaporization. The analysis of treatment and observation within a year and a half showed that in a group of children, who received a combination treatment, including Viferon therapy and removal of verrucas by 2 surgical methods. No backset of a disease detected. In general, the findings of the research pointed out the high efficiency of topical and systemic Viferon medications, as well as combination method of verruca removal in complex treatment of viral papilloma skin infection among the children.Key words: interferon status of children, interferon al'fa 2b, verrucas, viral papilloma infection.

  5. Viral kinetics of Enterovirus 71 in human abdomyosarcoma cells

    Science.gov (United States)

    Lu, Jing; He, Ya-Qing; Yi, Li-Na; Zan, Hong; Kung, Hsiang-Fu; He, Ming-Liang

    2011-01-01

    AIM: To characterise the viral kinetics of enterovirus 71 (EV71). METHODS: In this study, human rhabdomyosarcoma (RD) cells were infected with EV71 at different multiplicity of infection (MOI). After infection, the cytopathic effect (CPE) was monitored and recorded using a phase contrast microscope associated with a CCD camera at different time points post viral infection (0, 6, 12, 24 h post infection). Cell growth and viability were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in both EV71 infected and mock infected cells at each time point. EV71 replication kinetics in RD cells was determined by measuring the total intracellular viral RNA with real-time reverse-transcription polymerase chain reaction (qRT-PCR). Also, the intracellular and extracellular virion RNA was isolated and quantified at different time points to analyze the viral package and secretion. The expression of viral protein was determined by analyze the levels of viral structure protein VP1 with Western blotting. RESULTS: EV71 infection induced a significant CPE as early as 6 h post infection (p.i.) in both RD cells infected with high ratio of virus (MOI 10) and low ratio of virus (MOI 1). In EV71 infected cells, the cell growth was inhibited and the number of viable cells was rapidly decreased in the later phase of infection. EV71 virions were uncoated immediately after entry. The intracellular viral RNA began to increase at as early as 3 h p.i. and the exponential increase was found between 3 h to 6 h p.i. in both infected groups. For viral structure protein synthesis, results from western-blot showed that intracellular viral protein VP1 could not be detected until 6 h p.i. in the cells infected at either MOI 1 or MOI 10; and reached the peak at 9 h p.i. in the cells infected with EV71 at both MOI 1 and MOI 10. Simultaneously, the viral package and secretion were also actively processed as the virus underwent rapid replication. The viral package kinetics

  6. Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at early and late times after infection.

    Science.gov (United States)

    Price, Alexander M; Dai, Joanne; Bazot, Quentin; Patel, Luv; Nikitin, Pavel A; Djavadian, Reza; Winter, Peter S; Salinas, Cristina A; Barry, Ashley Perkins; Wood, Kris C; Johannsen, Eric C; Letai, Anthony; Allday, Martin J; Luftig, Micah A

    2017-04-20

    Latent Epstein-Barr virus (EBV) infection is causally linked to several human cancers. EBV expresses viral oncogenes that promote cell growth and inhibit the apoptotic response to uncontrolled proliferation. The EBV oncoprotein LMP1 constitutively activates NFκB and is critical for survival of EBV-immortalized B cells. However, during early infection EBV induces rapid B cell proliferation with low levels of LMP1 and little apoptosis. Therefore, we sought to define the mechanism of survival in the absence of LMP1/NFκB early after infection. We used BH3 profiling to query mitochondrial regulation of apoptosis and defined a transition from uninfected B cells (BCL-2) to early-infected (MCL-1/BCL-2) and immortalized cells (BFL-1). This dynamic change in B cell survival mechanisms is unique to virus-infected cells and relies on regulation of MCL-1 mitochondrial localization and BFL-1 transcription by the viral EBNA3A protein. This study defines a new role for EBNA3A in the suppression of apoptosis with implications for EBV lymphomagenesis.

  7. Early viral replication and induced or constitutive immunity in rainbow trout families with differential resistance to Infectious hematopoietic necrosis virus (IHNV)

    Science.gov (United States)

    Purcell, M.K.; LaPatra, S.E.; Woodson, J.C.; Kurath, G.; Winton, J.R.

    2010-01-01

    The main objective of this study was to assess correlates of innate resistance in rainbow trout full-sibling families that differ in susceptibility to Infectious hematopoietic necrosis virus (IHNV). As part of a commercial breeding program, full-sibling families were challenged with IHNV by waterborne exposure at the 1 g size to determine susceptibility to IHNV. Progeny from select families (N = 7 families) that varied in susceptibility (ranging from 32 to 90% cumulative percent mortality (CPM)) were challenged again at the 10 g size by intra-peritoneal injection and overall mortality, early viral replication and immune responses were evaluated. Mortality challenges included 20–40 fish per family while viral replication and immune response studies included 6 fish per family at each time point (24, 48 and 72 h post-infection (hpi)). CPM at the 1 g size was significantly correlated with CPM at the 10 g size, indicating that inherent resistance was a stable trait irrespective of size. In the larger fish, viral load was measured by quantitative reverse-transcriptase PCR in the anterior kidney and was a significant predictor of family disease outcome at 48 hpi. Type I interferon (IFN) transcript levels were significantly correlated with an individual's viral load at 48 and 72 hpi, while type II IFN gene expression was significantly correlated with an individual's viral load at 24 and 48 hpi. Mean family type I but not type II IFN gene expression was weakly associated with susceptibility at 72 hpi. There was no association between mean family susceptibility and the constitutive expression of a range of innate immune genes (e.g. type I and II IFN pathway genes, cytokine and viral recognition receptor genes). The majority of survivors from the challenge had detectable serum neutralizing antibody titers but no trend was observed among families. This result suggests that even the most resistant families experienced sufficient levels of viral replication to trigger specific

  8. Novel microRNA-like viral small regulatory RNAs arising during human hepatitis A virus infection.

    Science.gov (United States)

    Shi, Jiandong; Sun, Jing; Wang, Bin; Wu, Meini; Zhang, Jing; Duan, Zhiqing; Wang, Haixuan; Hu, Ningzhu; Hu, Yunzhang

    2014-10-01

    MicroRNAs (miRNAs), including host miRNAs and viral miRNAs, play vital roles in regulating host-virus interactions. DNA viruses encode miRNAs that regulate the viral life cycle. However, it is generally believed that cytoplasmic RNA viruses do not encode miRNAs, owing to inaccessible cellular miRNA processing machinery. Here, we provide a comprehensive genome-wide analysis and identification of miRNAs that were derived from hepatitis A virus (HAV; Hu/China/H2/1982), which is a typical cytoplasmic RNA virus. Using deep-sequencing and in silico approaches, we identified 2 novel virally encoded miRNAs, named hav-miR-1-5p and hav-miR-2-5p. Both of the novel virally encoded miRNAs were clearly detected in infected cells. Analysis of Dicer enzyme silencing demonstrated that HAV-derived miRNA biogenesis is Dicer dependent. Furthermore, we confirmed that HAV mature miRNAs were generated from viral miRNA precursors (pre-miRNAs) in host cells. Notably, naturally derived HAV miRNAs were biologically and functionally active and induced post-transcriptional gene silencing (PTGS). Genomic location analysis revealed novel miRNAs located in the coding region of the viral genome. Overall, our results show that HAV naturally generates functional miRNA-like small regulatory RNAs during infection. This is the first report of miRNAs derived from the coding region of genomic RNA of a cytoplasmic RNA virus. These observations demonstrate that a cytoplasmic RNA virus can naturally generate functional miRNAs, as DNA viruses do. These findings also contribute to improved understanding of host-RNA virus interactions mediated by RNA virus-derived miRNAs. © FASEB.

  9. Viral infection causes rapid sensitization to lipopolysaccharide: central role of IFN-alpha beta

    DEFF Research Database (Denmark)

    Nansen, A; Randrup Thomsen, A

    2001-01-01

    LPS is the major active agent in the pathogenesis of Gram-negative septic shock. In this report we have studied the influence of concurrent viral infection on the outcome of LPS-induced shock. We find that infection with vesicular stomatitis virus sensitizes mice to LPS at an early time point...... following infection. Treatment of mice with the chemical IFN inducer, polyinosinic:polycytidylic acid, has a similar effect. This hypersensitivity to LPS correlated with hyperproduction of TNF-alpha in vivo. The cellular and molecular mechanisms underlying this phenomenon were investigated using Ab......-depleted and gene-targeted mice. Our results revealed that while NK cell depletion and elimination of IFN-gamma partially protected against the sensitizing effects of vesicular stomatitis virus and polyinosinic:polycytidylic acid, the most striking effect was observed in IFN-alphabetaR-deficient mice. Thus...

  10. Eicosanoids and Respiratory Viral Infection: Coordinators of Inflammation and Potential Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Mary K. McCarthy

    2012-01-01

    Full Text Available Viruses are frequent causes of respiratory infection, and viral respiratory infections are significant causes of hospitalization, morbidity, and sometimes mortality in a variety of patient populations. Lung inflammation induced by infection with common respiratory pathogens such as influenza and respiratory syncytial virus is accompanied by increased lung production of prostaglandins and leukotrienes, lipid mediators with a wide range of effects on host immune function. Deficiency or pharmacologic inhibition of prostaglandin and leukotriene production often results in a dampened inflammatory response to acute infection with a respiratory virus. These mediators may, therefore, serve as appealing therapeutic targets for disease caused by respiratory viral infection.

  11. Dengue viral infection monitoring from diagnostic to recovery using Raman spectroscopy

    International Nuclear Information System (INIS)

    Firdous, Shamaraz; Anwar, Shahzad

    2015-01-01

    Raman spectroscopy has been found useful for monitoring the dengue patient diagnostic and recovery after infection. In the present work, spectral changes that occurred in the blood sera of a dengue infected patient and their possible utilization for monitoring of infection and recovery were investigated using 532 nm wavelength of light. Raman spectrum peaks for normal and after recovery of dengue infection are observed at 1527, 1170, 1021 cm −1 attributed to guanine, adenine, TRP (protein) carbohydrates peak for solids, and skeletal C–C stretch of lipids acyl chains. Where in the dengue infected patient Raman peaks are at 1467, 1316, 1083, and 860 attributed to CH2/CH3 deformation of lipids and collagen, guanine (B, Z-marker), lipids and protein bands. Due to antibodies and antigen reactions the portions and lipids concentration totally changes in dengue viral infection compared to normal blood. These chemical changes in blood sera of dengue viral infection in human blood may be used as possible markers to indicate successful remission and suggest that Raman spectroscopy may provide a rapid optical method for continuous monitoring or evaluation of a protein bands and an antibodies population. Accumulate acquisition mode was used to reduce noise and thermal fluctuation and improve signal to noise ratio. This in vitro dengue infection monitoring methodology will lead in vivo noninvasive on-line monitoring and screening of viral infected patients and their recovery. (letter)

  12. Respiratory viral infections in infants with clinically suspected pertussis.

    Science.gov (United States)

    Ferronato, Angela E; Gilio, Alfredo E; Vieira, Sandra E

    2013-01-01

    to evaluate the frequency of respiratory viral infections in hospitalized infants with clinical suspicion of pertussis, and to analyze their characteristics at hospital admission and clinical outcomes. a historical cohort study was performed in a reference service for pertussis, in which the research of respiratory viruses was also a routine for infants hospitalized with respiratory problems. All infants reported as suspected cases of pertussis were included. Tests for Bordetella pertussis (BP) (polymerase chain reaction/culture) and for respiratory viruses (RVs) (immunofluorescence) were performed. Patients who received macrolides before hospitalization were excluded. Clinical data were obtained from medical records. Among the 67 patients studied, BP tests were positive in 44%, and 26% were positive for RV. There was no etiological identification in 35%, and RV combined with BP was identified in 5%. All patients had similar demographic characteristics. Cough followed by inspiratory stridor or cyanosis was a strong predictor of pertussis, as well as prominent leukocytosis and lymphocytosis. Rhinorrhea and dyspnea were more frequent in viral infections. Macrolides were discontinued in 40% of patients who tested positive for RV and negative for BP. the results suggest that viral infection can be present in hospitalized infants with clinical suspicion of pertussis, and etiological tests may enable a reduction in the use of macrolides in some cases. However, the etiological diagnosis of respiratory virus infection, by itself, does not exclude the possibility of infection with BP. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  13. A temporal gate for viral enhancers to co-opt Toll-like-receptor transcriptional activation pathways upon acute infection.

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    Kai A Kropp

    2015-04-01

    Full Text Available Viral engagement with macrophages activates Toll-Like-Receptors (TLRs and viruses must contend with the ensuing inflammatory responses to successfully complete their replication cycle. To date, known counter-strategies involve the use of viral-encoded proteins that often employ mimicry mechanisms to block or redirect the host response to benefit the virus. Whether viral regulatory DNA sequences provide an opportunistic strategy by which viral enhancer elements functionally mimic innate immune enhancers is unknown. Here we find that host innate immune genes and the prototypical viral enhancer of cytomegalovirus (CMV have comparable expression kinetics, and positively respond to common TLR agonists. In macrophages but not fibroblasts we show that activation of NFκB at immediate-early times of infection is independent of virion-associated protein, M45. We find upon virus infection or transfection of viral genomic DNA the TLR-agonist treatment results in significant enhancement of the virus transcription-replication cycle. In macrophage time-course infection experiments we demonstrate that TLR-agonist stimulation of the viral enhancer and replication cycle is strictly delimited by a temporal gate with a determined half-maximal time for enhancer-activation of 6 h; after which TLR-activation blocks the viral transcription-replication cycle. By performing a systematic siRNA screen of 149 innate immune regulatory factors we identify not only anticipated anti-viral and pro-viral contributions but also new factors involved in the CMV transcription-replication cycle. We identify a central convergent NFκB-SP1-RXR-IRF axis downstream of TLR-signalling. Activation of the RXR component potentiated direct and indirect TLR-induced activation of CMV transcription-replication cycle; whereas chromatin binding experiments using wild-type and enhancer-deletion virus revealed IRF3 and 5 as new pro-viral host transcription factor interactions with the CMV enhancer in

  14. Patterns and rates of viral evolution in HIV-1 subtype B infected females and males.

    Directory of Open Access Journals (Sweden)

    Michael J Dapp

    Full Text Available Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS. However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men. We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS participants who had not received combination antiretroviral therapy (ART. This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes. No differences in ensuing nucleotide substitution rates were found between the female and male cohorts studied herein. As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017, and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region. These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.

  15. Rabies Virus Infection Induces the Formation of Stress Granules Closely Connected to the Viral Factories.

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    Jovan Nikolic

    2016-10-01

    Full Text Available Stress granules (SGs are membrane-less dynamic structures consisting of mRNA and protein aggregates that form rapidly in response to a wide range of environmental cellular stresses and viral infections. They act as storage sites for translationally silenced mRNAs under stress conditions. During viral infection, SG formation results in the modulation of innate antiviral immune responses, and several viruses have the ability to either promote or prevent SG assembly. Here, we show that rabies virus (RABV induces SG formation in infected cells, as revealed by the detection of SG-marker proteins Ras GTPase-activating protein-binding protein 1 (G3BP1, T-cell intracellular antigen 1 (TIA-1 and poly(A-binding protein (PABP in the RNA granules formed during viral infection. As shown by live cell imaging, RABV-induced SGs are highly dynamic structures that increase in number, grow in size by fusion events, and undergo assembly/disassembly cycles. Some SGs localize in close proximity to cytoplasmic viral factories, known as Negri bodies (NBs. Three dimensional reconstructions reveal that both structures remain distinct even when they are in close contact. In addition, viral mRNAs synthesized in NBs accumulate in the SGs during viral infection, revealing material exchange between both compartments. Although RABV-induced SG formation is not affected in MEFs lacking TIA-1, TIA-1 depletion promotes viral translation which results in an increase of viral replication indicating that TIA-1 has an antiviral effect. Inhibition of PKR expression significantly prevents RABV-SG formation and favors viral replication by increasing viral translation. This is correlated with a drastic inhibition of IFN-B gene expression indicating that SGs likely mediate an antiviral response which is however not sufficient to fully counteract RABV infection.

  16. Safety and immunogenicity of therapeutic DNA vaccination in individuals treated with antiretroviral therapy during acute/early HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Eric S Rosenberg

    2010-05-01

    Full Text Available An effective therapeutic vaccine that could augment immune control of HIV-1 replication may abrogate or delay the need for antiretroviral therapy. AIDS Clinical Trials Group (ACTG A5187 was a phase I/II, randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of an HIV-1 DNA vaccine (VRC-HVDNA 009-00-VP in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. (clinicaltrials.gov NCT00125099Twenty healthy HIV-1 infected subjects who were treated with antiretroviral therapy during acute/early HIV-1 infection and had HIV-1 RNA<50 copies/mL were randomized to receive either vaccine or placebo. The objectives of this study were to evaluate the safety and immunogenicity of the vaccine. Following vaccination, subjects interrupted antiretroviral treatment, and set-point HIV-1 viral loads and CD4 T cell counts were determined 17-23 weeks after treatment discontinuation.Twenty subjects received all scheduled vaccinations and discontinued antiretroviral therapy at week 30. No subject met a primary safety endpoint. No evidence of differences in immunogenicity were detected in subjects receiving vaccine versus placebo. There were also no significant differences in set-point HIV-1 viral loads or CD4 T cell counts following treatment discontinuation. Median set-point HIV-1 viral loads after treatment discontinuation in vaccine and placebo recipients were 3.5 and 3.7 log(10 HIV-1 RNA copies/mL, respectively.The HIV-1 DNA vaccine (VRC-HIVDNA 009-00-VP was safe but poorly immunogenic in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. Viral set-points were similar between vaccine and placebo recipients following treatment interruption. However, median viral load set-points in both groups were lower than in historical controls, suggesting a possible role for antiretroviral therapy in persons with acute or early HIV-1 infection and supporting the safety of

  17. Final Technical Report: Viral Infection of Subsurface Microorganisms and Metal/Radionuclide Transport

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Karrie A.; Bender, Kelly S.; Li, Yusong

    2013-09-28

    Microbially mediated metabolisms have been identified as a significant factor either directly or indirectly impacting the fate and transport of heavy metal/radionuclide contaminants. To date microorganisms have been isolated from contaminated environments. Examination of annotated finished genome sequences of many of these subsurface isolates from DOE sites, revealed evidence of prior viral infection. To date the role that viruses play influencing microbial mortality and the resulting community structure which directly influences biogeochemical cycling in soils and sedimentary environments remains poorly understood. The objective of this exploratory study was to investigate the role of viral infection of subsurface bacteria and the formation of contaminant-bearing viral particles. This objective was approached by examining the following working hypotheses: (i) subsurface microorganisms are susceptible to viral infections by the indigenous subsurface viral community, and (ii) viral surfaces will adsorb heavy metals and radionuclides. Our results have addressed basic research needed to accomplish the BER Long Term Measure to provide sufficient scientific understanding such that DOE sites would be able to incorporate coupled physical, chemical and biological processes into decision making for environmental remediation or natural attenuation and long-term stewardship by establishing viral-microbial relationships on the subsequent fate and transport of heavy metals and radionuclides. Here we demonstrated that viruses play a significant role in microbial mortality and community structure in terrestrial subsurface sedimentary systems. The production of viral-like particles within subsurface sediments in response to biostimulation with dissolved organic carbon and a terminal electron acceptor resulted in the production of viral-like particles. Organic carbon alone did not result in significant viral production and required the addition of a terminal electron acceptor

  18. Peripheral immunophenotype and viral promoter variants during the asymptomatic phase of feline immunodeficiency virus infection.

    Science.gov (United States)

    Murphy, B; Hillman, C; McDonnel, S

    2014-01-22

    Feline immunodeficiency virus (FIV)-infected cats enter a clinically asymptomatic phase during chronic infection. Despite the lack of overt clinical disease, the asymptomatic phase is characterized by persistent immunologic impairment. In the peripheral blood obtained from cats experimentally infected with FIV-C for approximately 5 years, we identified a persistent inversion of the CD4/CD8 ratio. We cloned and sequenced the FIV-C long terminal repeat containing the viral promoter from cells infected with the inoculating virus and from in vivo-derived peripheral blood mononuclear cells and CD4 T cells isolated at multiple time points throughout the asymptomatic phase. Relative to the inoculating virus, viral sequences amplified from cells isolated from all of the infected animals demonstrated multiple single nucleotide mutations and a short deletion within the viral U3, R and U5 regions. A transcriptionally inactivating proviral mutation in the U3 promoter AP-1 site was identified at multiple time points from all of the infected animals but not within cell-associated viral RNA. In contrast, no mutations were identified within the sequence of the viral dUTPase gene amplified from PBMC isolated at approximately 5 years post-infection relative to the inoculating sequence. The possible implications of these mutations to viral pathogenesis are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Impact of Early-Life Exposures to Infections, Antibiotics, and Vaccines on Perinatal and Long-term Health and Disease

    Directory of Open Access Journals (Sweden)

    Steven L. Raymond

    2017-06-01

    Full Text Available Essentially, all neonates are exposed to infections, antibiotics, or vaccines early in their lives. This is especially true for those neonates born underweight or premature. In contrast to septic adults and children who are at an increased risk for subsequent infections, exposure to infection during the neonatal period is not associated with an increased risk of subsequent infection and may be paradoxically associated with reductions in late-onset sepsis (LOS in the most premature infants. Perinatal inflammation is also associated with a decreased incidence of asthma and atopy later in life. Conversely, septic neonates are at increased risk of impaired long-term neurodevelopment. While the positive effects of antibiotics in the setting of infection are irrefutable, prolonged administration of broad-spectrum, empiric antibiotics in neonates without documented infection is associated with increased risk of LOS, necrotizing enterocolitis, or death. Vaccines provide a unique opportunity to prevent infection-associated disease; unfortunately, vaccinations have been largely unsuccessful when administered in the first month of life with the exception of vaccines against hepatitis B and tuberculosis. Future vaccines will require the use of novel adjuvants to overcome this challenge. This review describes the influence of infections, antibiotics, and vaccines during the first days of life, as well as the influence on future health and disease. We will also discuss potential immunomodulating therapies, which may serve to train the preterm immune system and reduce subsequent infectious burden without subjecting neonates to the risks accompanied by virulent pathogens.

  20. Viral hemagglutinin is involved in promoting the internalisation of Staphylococcus aureus into human pneumocytes during influenza A H1N1 virus infection.

    Science.gov (United States)

    Passariello, Claudio; Nencioni, Lucia; Sgarbanti, Rossella; Ranieri, Danilo; Torrisi, Maria Rosaria; Ripa, Sandro; Garaci, Enrico; Palamara, Anna Teresa

    2011-02-01

    Secondary pneumonia caused by Staphylococcus aureus is reemerging as a primary cause of excess mortality associated with infection by the influenza A virus. We have investigated in vitro the cellular and molecular mechanisms underlying this synergism. Experimental data show a significant increase in the efficiency of internalisation of S. aureus into cultured pneumocytes during the early phases of viral infection, while a relevant increase in the efficiency of adhesion is evident only later during viral infection, suggesting that the 2 effects are based on different molecular mechanisms. Data reported in this paper show that S. aureus cells can bind the viral hemagglutinin (HA) and that this binding promotes enhanced bacterial internalisation by 2 mechanisms: binding to HA exposed at the surface of infected cells and binding to free extracellular virions, enabling internalisation at high efficiency also in cells that are not infected by the virus. The affinity of binding that involves S. aureus and HA was shown to be enhanced by the reducing extracellular environment that the virus can generate. Copyright © 2010 Elsevier GmbH. All rights reserved.

  1. Viral phenotype, antiretroviral resistance and clinical evolution in human immunodeficiency virus-infected children.

    Science.gov (United States)

    Mellado, M J; Cilleruelo, M J; Ortiz, M; Villota, J; García, M; Perez-Jurado, M L; Barreiro, G; Martín-Fontelos, P; Bernal, A

    1997-11-01

    The syncytium-inducing (SI) viral phenotype and the emergence of viral strains resistant to zidovudine have been described in persons infected with HIV, and in some cases they have been associated with poor prognosis. HIV isolates obtained from 37 HIV-infected children were analyzed to determine whether the SI viral phenotype and the mutation on the 215 position of the reverse transcriptase (M215) could be used as markers of disease progression. We performed peripheral blood coculture mononuclear cells, and we analyzed the induction of syncytia using the MT-2 cell line. The emergence of mutations on the 215 position was determined by PCR. We found a statistically significant association (P < 0.05) between SI viral phenotype and (1) recurrent serious bacterial infections, (2) absolute CD4+ cell counts <2 SD, (3) progression to AIDS and (4) death. Sixty percent of the children treated with zidovudine developed 215 mutant viral strains without statistically significant association with clinical or immunologic findings. The SI viral phenotype was statistically associated with the presence of the 215 mutation (P < 0.05). SI viral phenotype is a marker associated with a poor clinical and immunologic progression of the disease and it may facilitate the emergence of mutant strains in children treated with zidovudine.

  2. Early RNA of adenovirus type 3 in permissive and abortive infections.

    OpenAIRE

    Groff, D E; Daniell, E

    1981-01-01

    Early adenovirus type 3 cytoplasmic polyadenylated RNAs from HeLa and BHK-21 cells were detected and mapped on the viral genome by gel blotting and hybridization techniques. The sizes and locations of the 16 adenovirus type 3 RNAs were identical in the two cell types, although relative molarities of the various RNA species differed. Each of the early adenovirus type 3 RNAs was associated with polysomes in both cell types, suggesting that the abortive infection of hamster cells does not result...

  3. Imaging Early Steps of Sindbis Virus Infection by Total Internal Reflection Fluorescence Microscopy

    Directory of Open Access Journals (Sweden)

    Youling Gu

    2011-01-01

    Full Text Available Sindbis virus (SINV is an alphavirus that has a broad host range and has been widely used as a vector for recombinant gene transduction, DNA-based vaccine production, and oncolytic cancer therapy. The mechanism of SINV entry into host cells has yet to be fully understood. In this paper, we used single virus tracking under total internal reflection fluorescence microscopy (TIRFM to investigate SINV attachment to cell surface. Biotinylated viral particles were labeled with quantum dots, which retained viral viability and infectivity. By time-lapse imaging, we showed that the SINV exhibited a heterogeneous dynamics on the surface of the host cells. Analysis of SINV motility demonstrated a two-step attachment reaction. Moreover, dual color TIRFM of GFP-Rab5 and SINV suggested that the virus was targeted to the early endosomes after endocytosis. These findings demonstrate the utility of quantum dot labeling in studying the early steps and behavior of SINV infection.

  4. p53 Activation following Rift Valley fever virus infection contributes to cell death and viral production.

    Directory of Open Access Journals (Sweden)

    Dana Austin

    Full Text Available Rift Valley fever virus (RVFV is an emerging viral zoonosis that is responsible for devastating outbreaks among livestock and is capable of causing potentially fatal disease in humans. Studies have shown that upon infection, certain viruses have the capability of utilizing particular cellular signaling pathways to propagate viral infection. Activation of p53 is important for the DNA damage signaling cascade, initiation of apoptosis, cell cycle arrest and transcriptional regulation of multiple genes. The current study focuses on the role of p53 signaling in RVFV infection and viral replication. These results show an up-regulation of p53 phosphorylation at several serine sites after RVFV MP-12 infection that is highly dependent on the viral protein NSs. qRT-PCR data showed a transcriptional up-regulation of several p53 targeted genes involved in cell cycle and apoptosis regulation following RVFV infection. Cell viability assays demonstrate that loss of p53 results in less RVFV induced cell death. Furthermore, decreased viral titers in p53 null cells indicate that RVFV utilizes p53 to enhance viral production. Collectively, these experiments indicate that the p53 signaling pathway is utilized during RVFV infection to induce cell death and increase viral production.

  5. Viral infection of human lung macrophages increases PDL1 expression via IFNβ.

    Directory of Open Access Journals (Sweden)

    Karl J Staples

    Full Text Available Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection. Ex-vivo viral infection models using influenza and RSV were established in human lung explants, isolated lung macrophages and monocyte-derived macrophages (MDM and analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung macrophages and MDM with X31 resulted in mean cellular infection rates of 18%, 18% and 29% respectively. Viral infection significantly increased cell surface expression of PDL1 on explant macrophages, lung macrophages and MDM but not explant epithelial cells. Infected MDM induced IFNγ release from autologous CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1 mRNA and IFNβ mRNA and protein release by MDM in response to influenza infection. Knockdown of IFNβ by siRNA, resulted in a 37.5% reduction in IFNβ gene expression in response to infection, and a significant decrease in PDL1 mRNA. Furthermore, when MDM were incubated with IFNβ, this cytokine caused increased expression of PDL1 mRNA. These data indicate that human macrophage PDL1 expression modulates CD8+ cell IFNγ release in response to virus and that this expression is regulated by autologous IFNβ production.

  6. Viral Small-RNA Analysis of Bombyx mori Larval Midgut during Persistent and Pathogenic Cytoplasmic Polyhedrosis Virus Infection.

    Science.gov (United States)

    Zografidis, Aris; Van Nieuwerburgh, Filip; Kolliopoulou, Anna; Apostolou-Karampelis, Konstantinos; Head, Steven R; Deforce, Dieter; Smagghe, Guy; Swevers, Luc

    2015-11-01

    The lepidopteran innate immune response against RNA viruses remains poorly understood, while in other insects several studies have highlighted an essential role for the exo-RNAi pathway in combating viral infection. Here, by using deep-sequencing technology for viral small-RNA (vsRNA) assessment, we provide evidence that exo-RNAi is operative in the silkworm Bombyx mori against both persistent and pathogenic infection of B. mori cytoplasmic polyhedrosis virus (BmCPV) which is characterized by a segmented double-stranded RNA (dsRNA) genome. Further, we show that Dicer-2 predominantly targets viral dsRNA and produces 20-nucleotide (nt) vsRNAs, whereas an additional pathway is responsive to viral mRNA derived from segment 10. Importantly, vsRNA distributions, which define specific hot and cold spot profiles for each viral segment, to a considerable degree overlap between Dicer-2-related (19 to 21 nt) and Dicer-2-unrelated vsRNAs, suggesting a common origin for these profiles. We found a degenerate motif significantly enriched at the cut sites of vsRNAs of various lengths which link an unknown RNase to the origins of vsRNAs biogenesis and distribution. Accordingly, the indicated RNase activity may be an important early factor for the host's antiviral defense in Lepidoptera. This work contributes to the elucidation of the lepidopteran antiviral response against infection of segmented double-stranded RNA (dsRNA) virus (CPV; Reoviridae) and highlights the importance of viral small-RNA (vsRNA) analysis for getting insights into host-pathogen interactions. Three vsRNA pathways are implicated in antiviral defense. For dsRNA, two pathways are proposed, either based on Dicer-2 cleavage to generate 20-nucleotide vsRNAs or based on the activity of an uncharacterized endo-RNase that cleaves the viral RNA substrate at a degenerate motif. The analysis also indicates the existence of a degradation pathway that targets the positive strand of segment 10. Copyright © 2015, American

  7. Combined administration of oseltamivir and hochu-ekki-to (TJ-41) dramatically decreases the viral load in lungs of senescence-accelerated mice during influenza virus infection.

    Science.gov (United States)

    Ohgitani, Eriko; Kita, Masakazu; Mazda, Osam; Imanishi, Jiro

    2014-02-01

    To enhance the effect of anti-influenza-virus agent treatment, the effect of combined administration of oseltamivir phosphate and hochu-ekki-to (Japanese traditional herbal medicine, HET) on early viral clearance was examined. Senescence-accelerated mice were given HET in drinking water for 2 weeks, followed by intranasal infection with influenza A virus strain PR8. After 4 hours of infection, oseltamivir was administered orally for 5 days. The viral loads in the lungs of the group receiving combined treatment were dramatically lower when compared with the viral loads in the lungs of the group receiving oseltamivir alone. HET significantly increased the induction of IL-1β and TNF-α in the lungs of PR8-infected mice and stimulated alveolar macrophage phagocytosis. From these results, we conclude that these functions may be responsible the increased effect on viral load reduction. Here, we show that the combined administration of oseltamivir and HET is very useful for influenza treatment in senescence-accelerated mice.

  8. Bm59 is an early gene, but is unessential for the propagation and assembly of Bombyx mori nucleopolyhedrovirus.

    Science.gov (United States)

    Hu, Xiaolong; Shen, Yunwang; Zheng, Qin; Wang, Guobao; Wu, Xiaofeng; Gong, Chengliang

    2016-02-01

    Bombyx mori nucleopolyhedrovirus (BmNPV) is a major pathogen that specifically infects the domestic silkworm and causes serious economic loss to sericulture around the world. The function of BmNPV Bm59 gene in the viral life cycle is inconclusive. To investigate the role of Bm59 during viral infection, the transcription initiation site and temporal expression of Bm59 were analyzed, and Bm59-knockout virus was generated through homologous recombination in Escherichia coli. The results showed that Bm59 is an early transcription gene with an atypia early transcriptional start motif. Budded virion (BV) production and DNA replication in the BmN cells transfected with the Bm59-knockout virus bacmid were similar to those in the cells transfected with the wild-type virus. Electron microscopy revealed that the occlusion-derived virus can be produced in cells infected with the Bm59-knockout virus. These results indicated that Bm59 is an early gene and is not essential for viral replication or assembly of BmNPV. These findings suggested that non-essential gene (Bm59) remained in the viral genome, which may interact with other viral/host genes in a certain situation.

  9. Mechanism of action and application of virocids in health care-associated viral infections

    Directory of Open Access Journals (Sweden)

    Babak Shahbaz

    2016-03-01

    Full Text Available Viruses are important causes of acute and chronic diseases in humans. Newer viruses are still being discovered. Apart from frequently causing infections in the general community, many types of viruses are significant nosocomial pathogens that with emerging viruses has become a real issue in medical field. There are specific treatments, vaccine and physical barrier to fight some of these infections. Health care-associated viral infections are an important source of patient’s morbidity and mortality. The method of sterilization or disinfection depends on the intended use of the medical devices (comprising critical, semicritical and noncritical items and failure to perform proper sterilization or disinfection of these items may leads to introduction of viruses, resulting in infection. Disinfection is an essential way in reducing or disruption of transmission of viruses by environmental surfaces, instruments and hands which achieves by chemical disinfectants and antiseptics, respectively. This review discusses about chemical agents with virocids properties (e.g. alcohols, chlorine compounds, formaldehyde, phenolic compounds, glutaraldehyde, ortho-phthaldehyde, hydrogen peroxide, peracetic acid, iodophor, ammonium compounds quaternary, bigunides and so on., mechanisms of action and their applications in health care-associated viral infection control. As well as, we described an overview for hierarchy of viruses in challenge with disinfantans, effective agents on viral inactivation, i.e.targect viruses, viral stability or survival duration time in enviromental surfaces and hands. We explained disinfection of surfaces, challenges in emerging viral pathogens inactivation, viral resistance to chemical disinfectants and antiseptics. Because, there are laboratory studies and clinical evidences for some viruses which viral resistance to biocide or failure to perform proper disinfection can lead to infection outbreaks. Also, we described virucidal

  10. Adenovirus-encoding virus-associated RNAs suppress HDGF gene expression to support efficient viral replication.

    Directory of Open Access Journals (Sweden)

    Saki Kondo

    Full Text Available Non-coding small RNAs are involved in many physiological responses including viral life cycles. Adenovirus-encoding small RNAs, known as virus-associated RNAs (VA RNAs, are transcribed throughout the replication process in the host cells, and their transcript levels depend on the copy numbers of the viral genome. Therefore, VA RNAs are abundant in infected cells after genome replication, i.e. during the late phase of viral infection. Their function during the late phase is the inhibition of interferon-inducible protein kinase R (PKR activity to prevent antiviral responses; recently, mivaRNAs, the microRNAs processed from VA RNAs, have been reported to inhibit cellular gene expression. Although VA RNA transcription starts during the early phase, little is known about its function. The reason may be because much smaller amount of VA RNAs are transcribed during the early phase than the late phase. In this study, we applied replication-deficient adenovirus vectors (AdVs and novel AdVs lacking VA RNA genes to analyze the expression changes in cellular genes mediated by VA RNAs using microarray analysis. AdVs are suitable to examine the function of VA RNAs during the early phase, since they constitutively express VA RNAs but do not replicate except in 293 cells. We found that the expression level of hepatoma-derived growth factor (HDGF significantly decreased in response to the VA RNAs under replication-deficient condition, and this suppression was also observed during the early phase under replication-competent conditions. The suppression was independent of mivaRNA-induced downregulation, suggesting that the function of VA RNAs during the early phase differs from that during the late phase. Notably, overexpression of HDGF inhibited AdV growth. This is the first report to show the function, in part, of VA RNAs during the early phase that may be contribute to efficient viral growth.

  11. Viral infection upregulates myostatin promoter activity in orange-spotted grouper (Epinephelus coioides).

    Science.gov (United States)

    Chen, Yi-Tien; Lin, Chao-Fen; Chen, Young-Mao; Lo, Chih-En; Chen, Wan-Erh; Chen, Tzong-Yueh

    2017-01-01

    Myostatin is a negative regulator of myogenesis and has been suggested to be an important factor in the development of muscle wasting during viral infection. The objective of this study was to characterize the main regulatory element of the grouper myostatin promoter and to study changes in promoter activity due to viral stimulation. In vitro and in vivo experiments indicated that the E-box E6 is a positive cis-and trans-regulation motif, and an essential binding site for MyoD. In contrast, the E-box E5 is a dominant negative cis-regulatory. The characteristics of grouper myostatin promoter are similar in regulation of muscle growth to that of other species, but mainly through specific regulatory elements. According to these results, we conducted a study to investigate the effect of viral infection on myostatin promoter activity and its regulation. The nervous necrosis virus (NNV) treatment significantly induced myostatin promoter activity. The present study is the first report describing that specific myostatin motifs regulate promoter activity and response to viral infection.

  12. Viral infection upregulates myostatin promoter activity in orange-spotted grouper (Epinephelus coioides.

    Directory of Open Access Journals (Sweden)

    Yi-Tien Chen

    Full Text Available Myostatin is a negative regulator of myogenesis and has been suggested to be an important factor in the development of muscle wasting during viral infection. The objective of this study was to characterize the main regulatory element of the grouper myostatin promoter and to study changes in promoter activity due to viral stimulation. In vitro and in vivo experiments indicated that the E-box E6 is a positive cis-and trans-regulation motif, and an essential binding site for MyoD. In contrast, the E-box E5 is a dominant negative cis-regulatory. The characteristics of grouper myostatin promoter are similar in regulation of muscle growth to that of other species, but mainly through specific regulatory elements. According to these results, we conducted a study to investigate the effect of viral infection on myostatin promoter activity and its regulation. The nervous necrosis virus (NNV treatment significantly induced myostatin promoter activity. The present study is the first report describing that specific myostatin motifs regulate promoter activity and response to viral infection.

  13. Diagnosing viral and bacterial respiratory infections in acute COPD exacerbations by an electronic nose: a pilot study.

    Science.gov (United States)

    van Geffen, Wouter H; Bruins, Marcel; Kerstjens, Huib A M

    2016-06-16

    Respiratory infections, viral or bacterial, are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). A rapid, point-of-care, and easy-to-use tool distinguishing viral and bacterial from other causes would be valuable in routine clinical care. An electronic nose (e-nose) could fit this profile but has never been tested in this setting before. In a single-center registered trial (NTR 4601) patients admitted with AECOPD were tested with the Aeonose(®) electronic nose, and a diagnosis of viral or bacterial infection was obtained by bacterial culture on sputa and viral PCR on nose swabs. A neural network with leave-10%-out cross-validation was used to assess the e-nose data. Forty three patients were included. In the bacterial infection model, 22 positive cases were tested versus the negatives; and similarly 18 positive cases were tested in the viral infection model. The Aeonose was able to distinguish between COPD-subjects suffering from a viral infection and COPD patients without infection, showing an area under the curve (AUC) of 0.74. Similarly, for bacterial infections, an AUC of 0.72 was obtained. The Aeonose e-nose yields promising results in 'smelling' the presence or absence of a viral or bacterial respiratory infection during an acute exacerbation of COPD. Validation of these results using a new and large cohort is required before introduction into clinical practice.

  14. Regulation of c-myc and c-fos mRNA levels by polyomavirus: distinct roles for the capsid protein VP1 and the viral early proteins

    International Nuclear Information System (INIS)

    Zullo, J.; Stiles, C.D.; Garcea, R.L.

    1987-01-01

    The levels of c-myc, c-fos, and JE mRNAs accumulate in a biphasic pattern following infection of quiescent BALB/c 3T3 mouse cells with polyomavirus. Maximal levels of c-myc and c-fos mRNAs were seen within 1 hr and were nearly undetectable at 6 hr after infection. At 12 hr after infection mRNA levels were again maximal and remained elevated thereafter. Empty virions (capsids) and recombinant VP 1 protein, purified from Escherichia coli, induced the early but not the late phase of mRNA accumulation. Virions, capsids, and recombinant VP 1 protein stimulated [ 3 H]thymidine nuclear labeling and c-myc mRNA accumulation in a dose-responsive manner paralleling their affinity for the cell receptor for polyoma. The second phase of mRNA accumulation is regulated by the viral early gene products, as shown by polyomavirus early gene mutants and by a transfected cell line (336a) expressing middle tumor antigen upon glucocorticoid addition. These results suggest that polyomavirus interacts with the cell membrane at the onset of infection to increase the levels of mRNA for the cellular genes associated with cell competence for DNA replication, and subsequently these levels are maintained by the action of the early viral proteins

  15. The risk of transfusion-transmissible viral infections in the Niger ...

    African Journals Online (AJOL)

    Background and objectives: Million\\'s of lives are saved each year through blood transfusion. Nevertheless people have increased risk of becoming infected with transfusion - transmissible viral infections through transfusion of blood and blood products that have not been tested correctly. This study was undertaken to ...

  16. MicroRNA Roles in the NF-κB Signaling Pathway during Viral Infections

    Directory of Open Access Journals (Sweden)

    Zeqian Gao

    2014-01-01

    Full Text Available NF-κB signaling network is a crucial component of innate immunity. miRNAs are a subtype of small noncoding RNAs, involved in regulation of gene expression at the posttranscriptional level. Increasing evidence has emerged that miRNAs play an important role in regulation of NF-κB signaling pathway during viral infections. Both host and viral miRNAs are attributed to modulation of NF-κB activity, thus affecting viral infection and clearance. Understandings of the mechanisms of these miRNAs will open a direction for development of novel antivirus drugs.

  17. The Ins and Outs of Viral Infection: Keystone Meeting Review

    Directory of Open Access Journals (Sweden)

    Sara W. Bird

    2014-09-01

    Full Text Available Newly observed mechanisms for viral entry, assembly, and exit are challenging our current understanding of the replication cycle of different viruses. To address and better understand these mechanisms, a Keystone Symposium was organized in the snowy mountains of Colorado (“The Ins and Outs of Viral Infection: Entry, Assembly, Exit, and Spread”; 30 March–4 April 2014, Beaver Run Resort, Breckenridge, Colorado, organized by Karla Kirkegaard, Mavis Agbandje-McKenna, and Eric O. Freed. The meeting served to bring together cell biologists, structural biologists, geneticists, and scientists expert in viral pathogenesis to discuss emerging mechanisms of viral ins and outs. The conference was organized around different phases of the viral replication cycle, including cell entry, viral assembly and post-assembly maturation, virus structure, cell exit, and virus spread. This review aims to highlight important topics and themes that emerged during the conference.

  18. Acute HBV infection in humanized chimeric mice has multiphasic viral kinetics.

    Science.gov (United States)

    Ishida, Yuji; Chung, Tje Lin; Imamura, Michio; Hiraga, Nobuhiko; Sen, Suranjana; Yokomichi, Hiroshi; Tateno, Chise; Canini, Laetitia; Perelson, Alan S; Uprichard, Susan L; Dahari, Harel; Chayama, Kazuaki

    2018-03-23

    Chimeric uPA/SCID mice reconstituted with humanized livers are useful for studying HBV infection in the absence of an adaptive immune response. However, the detailed characterization of HBV infection kinetics necessary to enable in-depth mechanistic studies in this novel in vivo HBV infection model is lacking. To characterize HBV kinetics post-inoculation (p.i.) to steady state, 42 mice were inoculated with HBV. Serum HBV DNA was frequently measured from 1 minute to 63 days p.i. Total intrahepatic HBV DNA, HBV cccDNA, and HBV RNA was measured in a subset of mice at 2, 4, 6, 10, and 13 weeks p.i. HBV half-life (t 1/2 ) was estimated using a linear mixed-effects model. During the first 6 h p.i. serum HBV declined in repopulated uPA/SCID mice with a t 1/2 =62 min [95%CI=59-67min]. Thereafter, viral decline slowed followed by a 2 day lower plateau. Subsequent viral amplification was multiphasic with an initial mean doubling time of t 2 =8±3 h followed by an interim plateau before prolonged amplification (t 2 =2±0.5 days) to a final HBV steady state of 9.3±0.3 log copies/ml. Serum HBV and intrahepatic HBV DNA were positively correlated (R 2 =0.98). HBV infection in uPA/SCID chimeric mice is highly dynamic despite the absence of an adaptive immune response. The serum HBV t 1/2 in humanized uPA/SCID mice was estimated to be ∼1 h regardless of inoculum size. The HBV acute infection kinetics presented here is an important step in characterizing this experimental model system so that it can be effectively used to elucidate the dynamics of the HBV lifecycle and thus possibly reveal effective antiviral drug targets. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  19. Hepatitis A virus-encoded miRNAs attenuate the accumulation of viral genomic RNAs in infected cells.

    Science.gov (United States)

    Shi, Jiandong; Sun, Jing; Wu, Meini; Hu, Ningzhu; Hu, Yunzhang

    2016-06-01

    The establishment of persistent infection with hepatitis A virus (HAV) is the common result of most HAV/cell culture systems. Previous observations show that the synthesis of viral RNAs is reduced during infection. However, the underlying mechanism is poorly understood. We characterized three HAV-encoded miRNAs in our previous study. In this study, we aim to investigate the impact of these miRNAs on the accumulation of viral RNAs. The results indicated that the synthesis of viral genomic RNAs was dramatically reduced (more than 75 % reduction, P viral miRNA mimics. Conversely, they were significantly increased (more than 3.3-fold addition, P viral miRNA inhibitors. The luciferase reporter assay of miRNA targets showed that viral miRNAs were fully complementary to specific sites of the viral plus or minus strand RNA and strongly inhibited their expressions. Further data showed that the relative abundance of viral genomic RNA fragments that contain miRNA targets was also dramatically reduced (more than 80 % reduction, P viral miRNAs were overexpressed with miRNA mimics. In contrast, they were significantly increased (approximately 2-fold addition, P viral miRNAs were inhibited with miRNA inhibitors. In conclusion, these data suggest a possible mechanism for the reduction of viral RNA synthesis during HAV infection. Thus, we propose that it is likely that RNA virus-derived miRNA could serve as a self-mediated feedback regulator during infection.

  20. Viral infection of the pregnant cervix predisposes to ascending bacterial infection

    Science.gov (United States)

    Racicot, Karen; Cardenas, Ingrid; Wünsche, Vera; Aldo, Paulomi; Guller, Seth; Means, Robert; Romero, Roberto; Mor, Gil

    2014-01-01

    Preterm birth is the major cause of neonatal mortality and morbidity, and bacterial infections that ascend from the lower female reproductive tract (FRT) are the most common route of uterine infection leading to preterm birth. The uterus and growing fetus are protected from ascending infection by the cervix, which controls and limits microbial access by the production of mucus, cytokines and anti-microbial peptides (AMPs). If this barrier is compromised, bacteria may enter the uterine cavity leading to preterm birth. Using a mouse model, we demonstrate, for the first time, that viral infection of the cervix, during pregnancy, reduces the capacity of the FRT to prevent bacterial infection of the uterus. This is due to differences in susceptibility of the cervix to infection by virus during pregnancy and the associated changes in TLR and AMP expression and function. We suggest that preterm labor is a polymicrobial disease, which requires a multifactorial approach for its prevention and treatment. PMID:23752614

  1. Comparison of viral infection in healthcare-associated pneumonia (HCAP) and community-acquired pneumonia (CAP)

    Science.gov (United States)

    Park, Kyoung Un; Lee, Sang Hoon; Lee, Yeon Joo; Park, Jong Sun; Cho, Young-Jae; Yoon, Ho Il; Lee, Choon-Taek

    2018-01-01

    Background Although viruses are known to be the second most common etiological factor in community-acquired pneumonia (CAP), the respiratory viral profile of the patients with healthcare-associated pneumonia (HCAP) has not yet been elucidated. We investigated the prevalence and the clinical impact of respiratory virus infection in adult patients with HCAP. Methods Patients admitted with HCAP or CAP, between January and December 2016, to a tertiary referral hospital in Korea, were prospectively enrolled, and virus identification was performed using reverse-transcription polymerase chain reaction (RT-PCR). Results Among 452 enrolled patients (224 with HCAP, 228 with CAP), samples for respiratory viruses were collected from sputum or endotracheal aspirate in 430 (95.1%) patients and from nasopharyngeal specimens in 22 (4.9%) patients. Eighty-seven (19.2%) patients had a viral infection, and the proportion of those with viral infection was significantly lower in the HCAP than in the CAP group (13.8% vs 24.6%, p = 0.004). In both the HCAP and CAP groups, influenza A was the most common respiratory virus, followed by entero-rhinovirus. The seasonal distributions of respiratory viruses were also similar in both groups. In the HCAP group, the viral infection resulted in a similar length of hospital stay and in-hospital mortality as viral–bacterial coinfection and bacterial infection, and the CAP group showed similar results. Conclusions The prevalence of viral infection in patients with HCAP was lower than that in patients with CAP, and resulted in a similar prognosis as viral–bacterial coinfection or bacterial infection. PMID:29447204

  2. Hepatitis B and C Viral Infections Among Blood Donors from Rural ...

    African Journals Online (AJOL)

    Hepatitis B and C Viral Infections Among Blood Donors from Rural Ghana. B Nkrumah, M Owusu, HO Frempong, P Averu. Abstract. Objective: To investigate the prevalence of Hepatitis B and C infections and co-infections among blood donors in a rural community of Ghana. Design: A retrospective study. Method: Samples ...

  3. Dynamics of a viral infection model with delayed CTL response and immune circadian rhythm

    International Nuclear Information System (INIS)

    Bai Zhenguo; Zhou Yicang

    2012-01-01

    This paper studies the global dynamics of a viral infection model that takes into account circadian rhythm and time delay in the CTL response. It is shown that the basic reproduction numbers, R 0 and R 1 , determine the outcome of viral infection. Numerical simulations demonstrate that the changes in the amplitude of lytic component can generate a variety of dynamical patterns, ranging from simple daily oscillation to multi-day dynamics and eventually chaos, whereas time delay can alter the period of oscillation for the larger level of periodic forcing. These results can help to explain the viral oscillation behaviors, which were observed in chronic HBV and HCV infection patients.

  4. Viral gene products and replication of the human immunodeficiency type 1 virus.

    Science.gov (United States)

    Morrow, C D; Park, J; Wakefield, J K

    1994-05-01

    The acquired immunodeficiency syndrome (AIDS) epidemic represents a modern-day plague that has not only resulted in a tragic loss of people from a wide spectrum of society but has reshaped our viewpoints regarding health care, the treatment of infectious diseases, and social issues regarding sexual behavior. There is little doubt now that the cause of the disease AIDS is a virus known as the human immunodeficiency virus (HIV). The HIV virus is a member of a large family of viruses termed retroviruses, which have as a hallmark the capacity to convert their RNA genome into a DNA form that then undergoes a process of integration into the host cell chromosome, followed by the expression of the viral genome and translation of viral proteins in the infected cell. This review describes the organization of the HIV-1 viral genome, the expression of viral proteins, as well as the functions of the accessory viral proteins in HIV replication. The replication of the viral genome is divided into two phases, the early phase and the late phase. The early phase consists of the interaction of the virus with the cell surface receptor (CD4 molecule in most cases), the uncoating and conversion of the viral RNA genome into a DNA form, and the integration into the host cell chromosome. The late phase consists of the expression of the viral proteins from the integrated viral genome, the translation of viral proteins, and the assembly and release of the virus. Points in the HIV-1 life cycle that are targets for therapeutic intervention are also discussed.

  5. UV-enhanced reactivation of minute-virus-of-mice: stimulation of a late step in the viral life cycle

    International Nuclear Information System (INIS)

    Rommelaere, J.; Vos, J.-M.; Cornelis, J.J.

    1981-01-01

    UV-enhanced reactivation of minute-virus-of-mice (MVM), an autonomous parvovirus, was studied in parasynchronous mouse A9 cells. The survival of UV-irradiated MVM is increased in cells which have been UV-irradiated prior to infection. UV-enhanced reactivation can be explained neither by facilitated plaque detection on UV-treated indicator cells, nor by altered kinetics of virus production by UV-irradiated cells. No effect of the multiplicity of infection on virus survival was detected in unirradiated or irradiated cells. The magnitude of UV-enhanced reactivation is a direct exponential function of the UV dose administered to the virus while virus survival is inversely proportional to the UV dosage. The expression of UV-enhanced reactivation can be activated in cells arrested in G 0 , it requires de novo protein synthesis and it is maximal when cells are irradiated 30 h before the onset of viral DNA replication. Early phases of the viral cycle, such as adsorption to cellular receptors, migration to the nucleus and uncoating were not affected by cell irradiation and are unlikely targets of the UV-enhanced reactivation function(s). These results, together with the single-strandedness of the viral genome, strongly suggest that the step stimulated in UV-irradiated cells functions concomitant with, or subsequent to, viral DNA replication. (author)

  6. Evaluation of green tea extract as a safe personal hygiene against viral infections.

    Science.gov (United States)

    Lee, Yun Ha; Jang, Yo Han; Kim, Young-Seok; Kim, Jinku; Seong, Baik Lin

    2018-01-01

    Viral infections often pose tremendous public health concerns as well as economic burdens. Despite the availability of vaccines or antiviral drugs, personal hygiene is considered as effective means as the first-hand measure against viral infections. The green tea catechins, in particular, epigallocatechin-3-gallate (EGCG), are known to exert potent antiviral activity. In this study, we evaluated the green tea extract as a safe personal hygiene against viral infections. Using the influenza virus A/Puerto Rico/8/34 (H1N1) as a model, we examined the duration of the viral inactivating activity of green tea extract (GTE) under prolonged storage at various temperature conditions. Even after the storage for 56 days at different temperatures, 0.1% GTE completely inactivated 10 6 PFU of the virus (6 log 10 reduction), and 0.01% and 0.05% GTE resulted in 2 log 10 reduction of the viral titers. When supplemented with 2% citric acid, 0.1% sodium benzoate, and 0.2% ascorbic acid as anti-oxidant, the inactivating activity of GTE was temporarily compromised during earlier times of storage. However, the antiviral activity of the GTE was steadily recovered up to similar levels with those of the same concentrations of GTE without the supplements, effectively prolonging the duration of the virucidal function over extended period. Cryo-EM and DLS analyses showed a slight increase in the overall size of virus particles by GTE treatment. The results suggest that the virucidal activity of GTE is mediated by oxidative crosslinking of catechins to the viral proteins and the change of physical properties of viral membranes. The durability of antiviral effects of GTE was examined as solution type and powder types over extended periods at various temperature conditions using human influenza A/H1N1 virus. GTE with supplements demonstrated potent viral inactivating activity, resulting in greater than 4 log 10 reduction of viral titers even after storage for up to two months at a wide range of

  7. Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections.

    Directory of Open Access Journals (Sweden)

    S Gnanakaran

    2011-09-01

    Full Text Available Here we have identified HIV-1 B clade Envelope (Env amino acid signatures from early in infection that may be favored at transmission, as well as patterns of recurrent mutation in chronic infection that may reflect common pathways of immune evasion. To accomplish this, we compared thousands of sequences derived by single genome amplification from several hundred individuals that were sampled either early in infection or were chronically infected. Samples were divided at the outset into hypothesis-forming and validation sets, and we used phylogenetically corrected statistical strategies to identify signatures, systematically scanning all of Env. Signatures included single amino acids, glycosylation motifs, and multi-site patterns based on functional or structural groupings of amino acids. We identified signatures near the CCR5 co-receptor-binding region, near the CD4 binding site, and in the signal peptide and cytoplasmic domain, which may influence Env expression and processing. Two signatures patterns associated with transmission were particularly interesting. The first was the most statistically robust signature, located in position 12 in the signal peptide. The second was the loss of an N-linked glycosylation site at positions 413-415; the presence of this site has been recently found to be associated with escape from potent and broad neutralizing antibodies, consistent with enabling a common pathway for immune escape during chronic infection. Its recurrent loss in early infection suggests it may impact fitness at the time of transmission or during early viral expansion. The signature patterns we identified implicate Env expression levels in selection at viral transmission or in early expansion, and suggest that immune evasion patterns that recur in many individuals during chronic infection when antibodies are present can be selected against when the infection is being established prior to the adaptive immune response.

  8. The type I interferon response during viral infections: a "SWOT" analysis.

    Science.gov (United States)

    Gaajetaan, Giel R; Bruggeman, Cathrien A; Stassen, Frank R

    2012-03-01

    The type I interferon (IFN) response is a strong and crucial moderator for the control of viral infections. The strength of this system is illustrated by the fact that, despite some temporary discomfort like a common cold or diarrhea, most viral infections will not cause major harm to the healthy immunocompetent host. To achieve this, the immune system is equipped with a wide array of pattern recognition receptors and the subsequent coordinated type I IFN response orchestrated by plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs). The production of type I IFN subtypes by dendritic cells (DCs), but also other cells is crucial for the execution of many antiviral processes. Despite this coordinated response, morbidity and mortality are still common in viral disease due to the ability of viruses to exploit the weaknesses of the immune system. Viruses successfully evade immunity and infection can result in aberrant immune responses. However, these weaknesses also open opportunities for improvement via clinical interventions as can be seen in current vaccination and antiviral treatment programs. The application of IFNs, Toll-like receptor ligands, DCs, and antiviral proteins is now being investigated to further limit viral infections. Unfortunately, a common threat during stimulation of immunity is the possible initiation or aggravation of autoimmunity. Also the translation from animal models to the human situation remains difficult. With a Strengths-Weaknesses-Opportunities-Threats ("SWOT") analysis, we discuss the interaction between host and virus as well as (future) therapeutic options, related to the type I IFN system. Copyright © 2011 John Wiley & Sons, Ltd.

  9. Diagnosis, gB genotype distribution and viral load of symptomatic congenitally infected CMV patients in Cuba.

    Science.gov (United States)

    Correa, C; Kourí, V; Pérez, L; Soto, Y; Limia, C

    2016-10-01

    Cytomegalovirus (CMV) is the leading cause of viral congenital infection. Some viral factors have been proposed to be CMV pathogenicity markers. The objective of this study was to investigate the frequency of congenital CMV infection in symptomatic patients and the possible association with the CMV glycoprotein B (gB) genotype and viral load. A total of 361 newborns (NB) and 158 pregnant women (PW) with clinically suspected CMV infection were enrolled. Studied samples included urine, saliva, serum, vaginal swabs and amniotic fluid. CMV infection was diagnosed by multiplex nested PCR. CMV gB genotyping was performed on infected samples, followed by viral load determination. Overall, 18.7% of the tested patients were positive for CMV infection, 19.7% of NB were congenitally infected and 16.5% of PW showed active CMV infection. gB-2 was the most prevalent genotype detected (39/97 patients). gB CMV mixed infections were detected in 12 patients. gB-2 was associated with mono-infections (PCMV load was statistically significant among patients presenting different clinical signs (P=0.04). This study showed that CMV is a frequent cause of congenital infection in symptomatic Cuban patients. Despite gB2 being the most frequently detected, gB-4 was the only genotype associated with clinical features (sepsis-like syndrome in NB). No other associations among specific genotypes and clinical characteristics were found. Further studies are needed to clarify the role that viral load and genotype play in the outcome of congenital infection.

  10. TLR3 signaling is either protective or pathogenic for the development of Theiler's virus-induced demyelinating disease depending on the time of viral infection

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    Jin Young-Hee

    2011-12-01

    Full Text Available Abstract Background We have previously shown that toll-like receptor 3 (TLR3-mediated signaling plays an important role in the induction of innate cytokine responses to Theiler's murine encephalomyelitis virus (TMEV infection. In addition, cytokine levels produced after TMEV infection are significantly higher in the glial cells of susceptible SJL mice compared to those of resistant C57BL/6 mice. However, it is not known whether TLR3-mediated signaling plays a protective or pathogenic role in the development of demyelinating disease. Methods SJL/J and B6;129S-Tlr3tm1Flv/J (TLR3KO-B6 mice, and TLR3KO-SJL mice that TLR3KO-B6 mice were backcrossed to SJL/J mice for 6 generations were infected with Theiler's murine encephalomyelitis virus (2 × 105 PFU with or without treatment with 50 μg of poly IC. Cytokine production and immune responses in the CNS and periphery of infected mice were analyzed. Results We investigated the role of TLR3-mediated signaling in the protection and pathogenesis of TMEV-induced demyelinating disease. TLR3KO-B6 mice did not develop demyelinating disease although they displayed elevated viral loads in the CNS. However, TLR3KO-SJL mice displayed increased viral loads and cellular infiltration in the CNS, accompanied by exacerbated development of demyelinating disease, compared to the normal littermate mice. Late, but not early, anti-viral CD4+ and CD8+ T cell responses in the CNS were compromised in TLR3KO-SJL mice. However, activation of TLR3 with poly IC prior to viral infection also exacerbated disease development, whereas such activation after viral infection restrained disease development. Activation of TLR3 signaling prior to viral infection hindered the induction of protective IFN-γ-producing CD4+ and CD8+ T cell populations. In contrast, activation of these signals after viral infection improved the induction of IFN-γ-producing CD4+ and CD8+ T cells. In addition, poly IC-pretreated mice displayed elevated PDL-1 and

  11. Severe hindrance of viral infection propagation in spatially extended hosts.

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    José A Capitán

    Full Text Available The production of large progeny numbers affected by high mutation rates is a ubiquitous strategy of viruses, as it promotes quick adaptation and survival to changing environments. However, this situation often ushers in an arms race between the virus and the host cells. In this paper we investigate in depth a model for the dynamics of a phenotypically heterogeneous population of viruses whose propagation is limited to two-dimensional geometries, and where host cells are able to develop defenses against infection. Our analytical and numerical analyses are developed in close connection to directed percolation models. In fact, we show that making the space explicit in the model, which in turn amounts to reducing viral mobility and hindering the infective ability of the virus, connects our work with similar dynamical models that lie in the universality class of directed percolation. In addition, we use the fact that our model is a multicomponent generalization of the Domany-Kinzel probabilistic cellular automaton to employ several techniques developed in the past in that context, such as the two-site approximation to the extinction transition line. Our aim is to better understand propagation of viral infections with mobility restrictions, e.g., in crops or in plant leaves, in order to inspire new strategies for effective viral control.

  12. Honeybee (Apis mellifera Venom Reinforces Viral Clearance during the Early Stage of Infection with Porcine Reproductive and Respiratory Syndrome Virus through the Up-Regulation of Th1-Specific Immune Responses

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    Jin-A Lee

    2015-05-01

    Full Text Available Porcine reproductive and respiratory syndrome (PRRS is a chronic and immunosuppressive viral disease that is responsible for substantial economic losses for the swine industry. Honeybee venom (HBV is known to possess several beneficial biological properties, particularly, immunomodulatory effects. Therefore, this study aimed at evaluating the effects of HBV on the immune response and viral clearance during the early stage of infection with porcine reproductive and respiratory syndrome virus (PRRSV in pigs. HBV was administered via three routes of nasal, neck, and rectal and then the pigs were inoculated with PRRSV intranasally. The CD4+/CD8+ cell ratio and levels of interferon (IFN-γ and interleukin (IL-12 were significantly increased in the HBV-administered healthy pigs via nasal and rectal administration. In experimentally PRRSV-challenged pigs with virus, the viral genome load in the serum, lung, bronchial lymph nodes and tonsil was significantly decreased, as was the severity of interstitial pneumonia, in the nasal and rectal administration group. Furthermore, the levels of Th1 cytokines (IFN-γ and IL-12 were significantly increased, along with up-regulation of pro-inflammatory cytokines (TNF-α and IL-1β with HBV administration. Thus, HBV administration—especially via the nasal or rectal route—could be a suitable strategy for immune enhancement and prevention of PRRSV infection in pigs.

  13. FEVER IN CHILDREN WITH RESPIRATORY VIRAL INFECTIONS: EFFECTIVE AND SAFE METHODS OF TREATMENT

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    T. E. Taranushenko

    2013-01-01

    Full Text Available One of the most important — the problem of treatment of fever in children with respiratory viral infections — is discussed in this article. It is fever as one of the first symptoms of disease which often frightens parents and leads to inappropriate and excess usage of antipyretic agents, which in its turn can cause unfavorable consequences. The authors represent their own data on frequency of antipyretic drugs usage in children with respiratory viral infections, as well as the answers of pediatricians to the questionnaires on methods of choice in temperature normalization. According to the modern Russian as well as European and American clinical guidelines on treatment of fever in children the management of selection of patients demanding antipyretic treatment is detailed, indications and contraindications to such therapy are described, the most effective methods of temperature normalization in children with acute respiratory infection are discussed. The authors suggested the data on recommended dosages of paracetamol, which were revised in 2011 by the UK Medicines Control Agency, to be very useful. The current information on advantages of ibuprofen in comparison to paracetamol in treatment of fever in children with respiratory viral infections is shown. The main target of this article is understanding and acceptance by pediatricians of the modern recommendation on differential and reasonable approach to administration of antipyretic drugs in children with respiratory viral infections.

  14. Persistent viral infections and immune aging.

    Science.gov (United States)

    Brunner, Stefan; Herndler-Brandstetter, Dietmar; Weinberger, Birgit; Grubeck-Loebenstein, Beatrix

    2011-07-01

    Immunosenescence comprises a set of dynamic changes occurring to both, the innate as well as the adaptive immune system that accompany human aging and result in complex manifestations of still poorly defined deficiencies in the elderly population. One of the most prominent alterations during aging is the continuous involution of the thymus gland which is almost complete by the age of 50. Consequently, the output of naïve T cells is greatly diminished in elderly individuals which puts pressure on homeostatic forces to maintain a steady T cell pool for most of adulthood. In a great proportion of the human population, this fragile balance is challenged by persistent viral infections, especially Cytomegalovirus (CMV), that oblige certain T cell clones to monoclonally expand repeatedly over a lifetime which then occupy space within the T cell pool. Eventually, these inflated memory T cell clones become exhausted and their extensive accumulation accelerates the age-dependent decline of the diversity of the T cell pool. As a consequence, infectious diseases are more frequent and severe in elderly persons and immunological protection following vaccination is reduced. This review therefore aims to shed light on how various types of persistent viral infections, especially CMV, influence the aging of the immune system and highlight potential measures to prevent the age-related decline in immune function. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Functional Role of Infective Viral Particles on Metal Reduction

    Energy Technology Data Exchange (ETDEWEB)

    Coates, John D.

    2014-04-01

    A proposed strategy for the remediation of uranium (U) contaminated sites was based on the immobilization of U by reducing the oxidized soluble U, U(VI), to form a reduced insoluble end product, U(IV). Previous studies identified Geobacter sp., including G. sulfurreducens and G. metallireducens, as predominant U(VI)-reducing bacteria under acetate-oxidizing and U(VI)-reducing conditions. Examination of the finished genome sequence annotation of the canonical metal reducing species Geobacter sulfurreducens strain PCA and G. metallireduceans strain GS-15 as well as the draft genome sequence of G. uraniumreducens strain Rf4 identified phage related proteins. In addition, the completed genome for Anaeromyxobacter dehalogenans and the draft genome sequence of Desulfovibrio desulfuricans strain G20, two more model metal-reducing bacteria, also revealed phage related sequences. The presence of these gene sequences indicated that Geobacter spp., Anaeromyxobacter spp., and Desulfovibrio spp. are susceptible to viral infection. Furthermore, viral populations in soils and sedimentary environments in the order of 6.4×10{sup 6}–2.7×10{sup 10} VLP’s cm{sup -3} have been observed. In some cases, viral populations exceed bacterial populations in these environments suggesting that a relationship may exist between viruses and bacteria. Our preliminary screens of samples collected from the ESR FRC indicated that viral like particles were observed in significant numbers. The objective of this study was to investigate the potential functional role viruses play in metal reduction specifically Fe(III) and U(VI) reduction, the environmental parameters affecting viral infection of metal reducing bacteria, and the subsequent effects on U transport.

  16. FIV establishes a latent infection in feline peripheral blood CD4+ T lymphocytes in vivo during the asymptomatic phase of infection

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    Murphy Brian

    2012-02-01

    Full Text Available Abstract Background Feline immunodeficiency virus (FIV is a lentivirus of cats that establishes a lifelong persistent infection with immunologic impairment. Results In an approximately 2 year-long experimental infection study, cats infected with a biological isolate of FIV clade C demonstrated undetectable plasma viral loads from 10 months post-infection onward. Viral DNA was detected in CD4+CD25+ and CD4+CD25- T cells isolated from infected cats whereas viral RNA was not detected at multiple time points during the early chronic phase of infection. Viral transcription could be reactivated in latently infected CD4+ T cells ex vivo as demonstrated by detectable FIV gag RNA and 2-long terminal repeat (LTR circle junctions. Viral LTR and gag sequences amplified from peripheral blood mononuclear cells during early and chronic stages of infection demonstrated minimal to no viral sequence variation. Conclusions Collectively, these findings are consistent with FIV latency in peripheral blood CD4+ T cells isolated from chronically infected cats. The ability to isolate latently FIV-infected CD4+ T lymphocytes from FIV-infected cats provides a platform for the study of in vivo mechanisms of lentiviral latency.

  17. 454-Pyrosequencing: A Molecular Battiscope for Freshwater Viral Ecology

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    David J. Rooks

    2010-07-01

    Full Text Available Viruses, the most abundant biological entities on the planet, are capable of infecting organisms from all three branches of life, although the majority infect bacteria where the greatest degree of cellular diversity lies. However, the characterization and assessment of viral diversity in natural environments is only beginning to become a possibility. Through the development of a novel technique for the harvest of viral DNA and the application of 454 pyrosequencing, a snapshot of the diversity of the DNA viruses harvested from a standing pond on a cattle farm has been obtained. A high abundance of viral genotypes (785 were present within the virome. The absolute numbers of lambdoid and Shiga toxin (Stx encoding phages detected suggested that the depth of sequencing had enabled recovery of only ca. 8% of the total virus population, numbers that agreed within less than an order of magnitude with predictions made by rarefaction analysis. The most abundant viral genotypes in the pond were bacteriophages (93.7%. The predominant viral genotypes infecting higher life forms found in association with the farm were pathogens that cause disease in cattle and humans, e.g. members of the Herpesviridae. The techniques and analysis described here provide a fresh approach to the monitoring of viral populations in the aquatic environment, with the potential to become integral to the development of risk analysis tools for monitoring the dissemination of viral agents of animal, plant and human diseases.

  18. Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children.

    Science.gov (United States)

    Herberg, Jethro A; Kaforou, Myrsini; Wright, Victoria J; Shailes, Hannah; Eleftherohorinou, Hariklia; Hoggart, Clive J; Cebey-López, Miriam; Carter, Michael J; Janes, Victoria A; Gormley, Stuart; Shimizu, Chisato; Tremoulet, Adriana H; Barendregt, Anouk M; Salas, Antonio; Kanegaye, John; Pollard, Andrew J; Faust, Saul N; Patel, Sanjay; Kuijpers, Taco; Martinón-Torres, Federico; Burns, Jane C; Coin, Lachlan J M; Levin, Michael

    Because clinical features do not reliably distinguish bacterial from viral infection, many children worldwide receive unnecessary antibiotic treatment, while bacterial infection is missed in others. To identify a blood RNA expression signature that distinguishes bacterial from viral infection in febrile children. Febrile children presenting to participating hospitals in the United Kingdom, Spain, the Netherlands, and the United States between 2009-2013 were prospectively recruited, comprising a discovery group and validation group. Each group was classified after microbiological investigation as having definite bacterial infection, definite viral infection, or indeterminate infection. RNA expression signatures distinguishing definite bacterial from viral infection were identified in the discovery group and diagnostic performance assessed in the validation group. Additional validation was undertaken in separate studies of children with meningococcal disease (n = 24) and inflammatory diseases (n = 48) and on published gene expression datasets. A 2-transcript RNA expression signature distinguishing bacterial infection from viral infection was evaluated against clinical and microbiological diagnosis. Definite bacterial and viral infection was confirmed by culture or molecular detection of the pathogens. Performance of the RNA signature was evaluated in the definite bacterial and viral group and in the indeterminate infection group. The discovery group of 240 children (median age, 19 months; 62% male) included 52 with definite bacterial infection, of whom 36 (69%) required intensive care, and 92 with definite viral infection, of whom 32 (35%) required intensive care. Ninety-six children had indeterminate infection. Analysis of RNA expression data identified a 38-transcript signature distinguishing bacterial from viral infection. A smaller (2-transcript) signature (FAM89A and IFI44L) was identified by removing highly correlated transcripts. When this 2-transcript

  19. Who Regulates Whom? An Overview of RNA Granules and Viral Infections

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    Natalia Poblete-Durán

    2016-06-01

    Full Text Available After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs, which are translationally silent sites of RNA triage and processing bodies (PBs, which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs.

  20. Genetic association of the functional CDHR3 genotype with early-onset adult asthma in Japanese populations

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    Jun Kanazawa

    2017-10-01

    Conclusions: Our study supports the concept that the CDHR3 variant is an important susceptibility factor for severe adult asthma in individuals who develop the disease in early life. The interaction between the CDHR3 variant and atopy indicates that genetic predisposition to early respiratory viral infection is combined with atopy in promoting asthma.

  1. Early life exposures and the risk of adult glioma.

    Science.gov (United States)

    Anic, Gabriella M; Madden, Melissa H; Sincich, Kelly; Thompson, Reid C; Nabors, L Burton; Olson, Jeffrey J; LaRocca, Renato V; Browning, James E; Pan, Edward; Egan, Kathleen M

    2013-09-01

    Exposure to common infections in early life may stimulate immune development and reduce the risk for developing cancer. Birth order and family size are proxies for the timing of exposure to childhood infections with several studies showing a reduced risk of glioma associated with a higher order of birth (and presumed younger age at infection). The aim of this study was to examine whether birth order, family size, and other early life exposures are associated with the risk of glioma in adults using data collected in a large clinic-based US case-control study including 889 glioma cases and 903 community controls. A structured interviewer-administered questionnaire was used to collect information on family structure, childhood exposures and other potential risk factors. Logistic regression was used to calculate odds ratios (OR) and corresponding 95% confidence intervals (CI) for the association between early life factors and glioma risk. Persons having any siblings were at significantly lower risk for glioma when compared to those reporting no siblings (OR=0.64; 95% CI 0.44-0.93; p=0.020). Compared to first-borns, individuals with older siblings had a significantly lower risk (OR=0.75; 95% CI 0.61-0.91; p=0.004). Birth weight, having been breast fed in infancy, and season of birth were not associated with glioma risk. The current findings lend further support to a growing body of evidence that early exposure to childhood infections reduces the risk of glioma onset in children and adults.

  2. Analysis of IAV Replication and Co-infection Dynamics by a Versatile RNA Viral Genome Labeling Method

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    Dan Dou

    2017-07-01

    Full Text Available Genome delivery to the proper cellular compartment for transcription and replication is a primary goal of viruses. However, methods for analyzing viral genome localization and differentiating genomes with high identity are lacking, making it difficult to investigate entry-related processes and co-examine heterogeneous RNA viral populations. Here, we present an RNA labeling approach for single-cell analysis of RNA viral replication and co-infection dynamics in situ, which uses the versatility of padlock probes. We applied this method to identify influenza A virus (IAV infections in cells and lung tissue with single-nucleotide specificity and to classify entry and replication stages by gene segment localization. Extending the classification strategy to co-infections of IAVs with single-nucleotide variations, we found that the dependence on intracellular trafficking places a time restriction on secondary co-infections necessary for genome reassortment. Altogether, these data demonstrate how RNA viral genome labeling can help dissect entry and co-infections.

  3. Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity

    International Nuclear Information System (INIS)

    Du, Lanying; Kao, Richard Y.; Zhou, Yusen; He, Yuxian; Zhao, Guangyu; Wong, Charlotte; Jiang, Shibo; Yuen, Kwok-Yung; Jin, Dong-Yan; Zheng, Bo-Jian

    2007-01-01

    The spike (S) protein of SARS coronavirus (SARS-CoV) has been known to recognize and bind to host receptors, whose conformational changes then facilitate fusion between the viral envelope and host cell membrane, leading to viral entry into target cells. However, other functions of SARS-CoV S protein such as proteolytic cleavage and its implications to viral infection are incompletely understood. In this study, we demonstrated that the infection of SARS-CoV and a pseudovirus bearing the S protein of SARS-CoV was inhibited by a protease inhibitor Ben-HCl. Also, the protease Factor Xa, a target of Ben-HCl abundantly expressed in infected cells, was able to cleave the recombinant and pseudoviral S protein into S1 and S2 subunits, and the cleavage was inhibited by Ben-HCl. Furthermore, this cleavage correlated with the infectivity of the pseudovirus. Taken together, our study suggests a plausible mechanism by which SARS-CoV cleaves its S protein to facilitate viral infection

  4. Host-derived viral transporter protein for nitrogen uptake in infected marine phytoplankton

    Science.gov (United States)

    Chambouvet, Aurélie; Milner, David S.; Attah, Victoria; Terrado, Ramón; Lovejoy, Connie; Moreau, Hervé; Derelle, Évelyne; Richards, Thomas A.

    2017-01-01

    Phytoplankton community structure is shaped by both bottom–up factors, such as nutrient availability, and top–down processes, such as predation. Here we show that marine viruses can blur these distinctions, being able to amend how host cells acquire nutrients from their environment while also predating and lysing their algal hosts. Viral genomes often encode genes derived from their host. These genes may allow the virus to manipulate host metabolism to improve viral fitness. We identify in the genome of a phytoplankton virus, which infects the small green alga Ostreococcus tauri, a host-derived ammonium transporter. This gene is transcribed during infection and when expressed in yeast mutants the viral protein is located to the plasma membrane and rescues growth when cultured with ammonium as the sole nitrogen source. We also show that viral infection alters the nature of nitrogen compound uptake of host cells, by both increasing substrate affinity and allowing the host to access diverse nitrogen sources. This is important because the availability of nitrogen often limits phytoplankton growth. Collectively, these data show that a virus can acquire genes encoding nutrient transporters from a host genome and that expression of the viral gene can alter the nutrient uptake behavior of host cells. These results have implications for understanding how viruses manipulate the physiology and ecology of phytoplankton, influence marine nutrient cycles, and act as vectors for horizontal gene transfer. PMID:28827361

  5. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection

    International Nuclear Information System (INIS)

    Nadarajah, Jeyaseelan; Madhusudhan, Kumble Seetharama; Yadav, Ajay Kumar; Gupta, Arun Kumar; Vikram, Naval Kumar

    2015-01-01

    Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT) scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF) and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI) revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR) hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made

  6. SPOC1-mediated antiviral host cell response is antagonized early in human adenovirus type 5 infection

    DEFF Research Database (Denmark)

    Schreiner, Sabrina; Kinkley, Sarah; Bürck, Carolin

    2013-01-01

    , and playing a role in DNA damage response. SPOC1 co-localized with viral replication centers in the host cell nucleus, interacted with Ad DNA, and repressed viral gene expression at the transcriptional level. We discovered that this SPOC1-mediated restriction imposed upon Ad growth is relieved by its...... viruses (HSV-1, HSV-2, HIV-1, and HCV) also depleted SPOC1 in infected cells. Our findings provide a general model for how pathogenic human viruses antagonize intrinsic SPOC1-mediated antiviral responses in their host cells. A better understanding of viral entry and early restrictive functions in host...

  7. Pharmacologic inhibition of COX-1 and COX-2 in influenza A viral infection in mice.

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    Michelle A Carey

    Full Text Available BACKGROUND: We previously demonstrated that cyclooxygenase (COX-1 deficiency results in greater morbidity and inflammation, whereas COX-2 deficiency leads to reduced morbidity, inflammation and mortality in influenza infected mice. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of COX-1 and COX-2 inhibitors in influenza A viral infection. Mice were given a COX-1 inhibitor (SC-560, a COX-2 inhibitor (celecoxib or no inhibitor beginning 2 weeks prior to influenza A viral infection (200 PFU and throughout the course of the experiment. Body weight and temperature were measured daily as indicators of morbidity. Animals were sacrificed on days 1 and 4 post-infection and bronchoalveolar lavage (BAL fluid was collected or daily mortality was recorded up to 2 weeks post-infection. Treatment with SC-560 significantly increased mortality and was associated with profound hypothermia and greater weight loss compared to celecoxib or control groups. On day 4 of infection, BAL fluid cells were modestly elevated in celecoxib treated mice compared to SC-560 or control groups. Viral titres were similar between treatment groups. Levels of TNF-alpha and G-CSF were significantly attenuated in the SC-560 and celecoxib groups versus control and IL-6 levels were significantly lower in BAL fluid of celecoxib treated mice versus control and versus the SC-560 group. The chemokine KC was significantly lower in SC-560 group versus control. CONCLUSIONS/SIGNIFICANCE: Treatment with a COX-1 inhibitor during influenza A viral infection is detrimental to the host whereas inhibition of COX-2 does not significantly modulate disease severity. COX-1 plays a critical role in controlling the thermoregulatory response to influenza A viral infection in mice.

  8. DMPD: Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune diseases. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18641647 Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune dise... (.csml) Show Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune diseases....iral infection andautoimmune diseases. Authors Gilliet M, Cao W, Liu YJ. Publication Nat Rev Immunol. 2008 A

  9. The importance of lytic and nonlytic immune responses in viral infections

    DEFF Research Database (Denmark)

    Wodarz, Dominik; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2002-01-01

    Antiviral immune effector mechanisms can be divided broadly into lytic and nonlytic components. We use mathematical models to investigate the fundamental question of which type of response is required to combat different types of viral infection. According to our model, the relative roles...... of the two types of component depend on the cytopathicity of the virus relative to its rate of replication. If the viral cytopathicity is low relative to the rate of viral replication, the model predicts that a combination of lytic and nonlytic effector mechanisms is likely to be required to resolve...

  10. [Relationship between viral load of human bocavirus and clinical characteristics in children with acute lower respiratory tract infection].

    Science.gov (United States)

    Ding, Xiao-Fang; Zhang, Bing; Zhong, Li-Li; Xie, Le-Yun; Xiao, Ni-Guang

    2017-03-01

    To investigate the prevalence of human bocavirus (HBoV) in children with acute lower respiratory tract infection and to explore the relationship between the viral load of HBoV and the clinical characteristics of acute lower respiratory tract infection in children. A total of 1 554 nasopharyngeal aspirates from children who were hospitalized due to acute lower respiratory tract infection between March 2011 and March 2014 were collected. Quantitative real-time PCR was used to detect 12 RNA and 2 DNA viruses, adenovirus (ADV) and HBoV, and to measure the viral load of HBoV in HBoV-positive children. A comprehensive analysis was performed with reference to clinical symptoms and indicators. In the 1 554 specimens, 1 212 (77.99%) were positive for viruses, and 275 (17.70%) were HBoV-positive. In HBoV-positive cases, 94.9% were aged infection, and 230 (83.64%) had mixed infection. There was no significant difference in viral load between children with single infection and mixed infection (P>0.05). The patients with fever had a significantly higher viral load than those without fever (Pacute lower respiratory tract infection (P>0.05). HBoV is one of the important pathogens of acute lower respiratory tract infection in children. Children with a higher viral load of HBoV are more likely to experience symptoms such as fever and wheezing. However, the severity of disease and mixed infection are not significantly related to viral load.

  11. A novel host-proteome signature for distinguishing between acute bacterial and viral infections.

    Directory of Open Access Journals (Sweden)

    Kfir Oved

    Full Text Available Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP, and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91, which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96. The signature was superior to any of the individual proteins (P<0.001, as well as routinely used clinical parameters and their combinations (P<0.001. It remained robust across different physiological systems

  12. PA from an H5N1 highly pathogenic avian influenza virus activates viral transcription and replication and induces apoptosis and interferon expression at an early stage of infection

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    Wang Qiang

    2012-06-01

    Full Text Available Abstract Background Although gene exchange is not likely to occur freely, reassortment between the H5N1 highly pathogenic avian influenza virus (HPAIV and currently circulating human viruses is a serious concern. The PA polymerase subunit of H5N1 HPAIV was recently reported to activate the influenza replicon activity. Methods The replicon activities of PR8 and WSN strains (H1N1 of influenza containing PA from HPAIV A/Cambodia/P0322095/2005 (H5N1 and the activity of the chimeric RNA polymerase were analyzed. A reassortant WSN virus containing the H5N1 Cambodia PA (C-PA was then reconstituted and its growth in cells and pathogenicity in mice examined. The interferon promoter, TUNEL, and caspase 3, 8, and 9 activities of C-PA-infected cells were compared with those of WSN-infected cells. Results The activity of the chimeric RNA polymerase was slightly higher than that of WSN, and C-PA replicated better than WSN in cells. However, the multi-step growth of C-PA and its pathogenicity in mice were lower than those of WSN. The interferon promoter, TUNEL, and caspase 3, 8, and 9 activities were strongly induced in early infection in C-PA-infected cells but not in WSN-infected cells. Conclusions Apoptosis and interferon were strongly induced early in C-PA infection, which protected the uninfected cells from expansion of viral infection. In this case, these classical host-virus interactions contributed to the attenuation of this strongly replicating virus.

  13. Influenza virus gene expression: viral RNA replication in vivo and in vitro

    International Nuclear Information System (INIS)

    Shapiro, G.I.

    1987-01-01

    To develop an overall scheme for the control of influenza virus gene expression, single-stranded M13 DNAs specific for the various genomic segments were used to analyze the synthesis of virus-specific RNAs in infected cells. The results showed that virus infection is divided into two distinct phases. During the early phase, the syntheses of specific virion RNAs (vRNAs), viral mRNAs, and viral proteins were coupled. This phase lasted for 2.5 hours in BHK-21 cells, the time when the rate of synthesis of all the viral mRNAs was maximal. During the late phase, the synthesis of all the vRNAs remained at or near maximum, whereas the rate of synthesis of all the viral mRNAs declined dramatically. Viral mRNA and protein syntheses were also not coupled, as the synthesis of all the viral proteins continued at maximum levels, indicating that protein synthesis during this phase was directed principally by previously synthesized viral mRNAs. Pulses with [ 3 H]uridine and nonaqueous fractionation of cells were used to show that influenza vRNA, like viral mRNAs, are synthesized in the nucleus and efficiently transported to the cytoplasm. In contrast, the full-length transcripts of the vRNAs, the templates for new vRNA synthesis, were synthesized only at early times, and remained sequestered in the nucleus to direct vRNA synthesis throughout infection

  14. Targeting membrane-bound viral RNA synthesis reveals potent inhibition of diverse coronaviruses including the middle East respiratory syndrome virus.

    Directory of Open Access Journals (Sweden)

    Anna Lundin

    2014-05-01

    Full Text Available Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs, a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6, a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV, and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.

  15. Perinatal Exposure to Environmental Tobacco Smoke (ETS Enhances Susceptibility to Viral and Secondary Bacterial Infections

    Directory of Open Access Journals (Sweden)

    Jocelyn A. Claude

    2012-10-01

    Full Text Available Studies suggest childhood exposure to environmental tobacco smoke (ETS leads to increased incidence of infections of the lower respiratory tract. The objective of this study was to determine whether perinatal exposure to ETS increases the incidence, morbidity and severity of respiratory influenza infection and whether a secondary bacterial challenge at the peak of a pre-existing viral infection creates an enhanced host-pathogen susceptibility to an opportunistic infection. Timed-pregnant female Balb/c mice were exposed to either ETS for 6 h/day, 7 d/week beginning on gestation day 14 and continuing with the neonates to 6 weeks of age. Control animals were exposed to filtered air (FA. At the end of exposure, mice were intranasally inoculated with a murine-adapted influenza A. One week later, an intranasal inoculation of S. aureus bacteria was administered. The respective treatment groups were: bacteria only, virus only or virus+bacteria for both FA and ETS-exposed animals for a total of six treatment groups. Animal behavior and body weights were documented daily following infection. Mice were necropsied 1-day post-bacterial infection. Bronchoalveolar lavage fluid (BALF cell analysis demonstrated perinatal exposure to ETS, compared to FA, leads to delayed but enhanced clinical symptoms and enhanced total cell influx into the lungs associated with viral infection followed by bacterial challenge. Viral infection significantly increases the number of neutrophils entering the lungs following bacterial challenge with either FA or ETS exposure, while the influx of lymphocytes and monocytes is significantly enhanced only by perinatal ETS exposure. There is a significant increase in peribronchiolar inflammation following viral infection in pups exposed to ETS compared with pups exposed to FA, but no change is noted in the degree of lung injury between FA and ETS-exposed animals following bacterial challenge. The data suggests perinatal exposure to ETS

  16. Impact of the Respiratory Microbiome on Host Responses to Respiratory Viral Infection

    Directory of Open Access Journals (Sweden)

    Maxime Pichon

    2017-11-01

    Full Text Available Viruses are responsible for most of both upper and lower acute respiratory infections (ARIs. The microbiome—the ecological community of microorganisms sharing the body space, which has gained considerable interest over the last decade—is modified in health and disease states. Even if most of these disturbances have been previously described in relation to chronic disorders of the gastrointestinal microbiome, after a short reminder of microbiome characteristics and methods of characterization, this review will describe the impact of the microbiome (mainly respiratory on host responses to viral ARIs. The microbiome has a direct environmental impact on the host cells but also an indirect impact on the immune system, by enhancing innate or adaptive immune responses. In microbial infections, especially in viral infections, these dramatic modifications could lead to a dramatic impact responsible for severe clinical outcomes. Studies focusing on the microbiome associated with transcriptomic analyses of the host response and deep characterization of the pathogen would lead to a better understanding of viral pathogenesis and open avenues for biomarker development and innovative therapeutics.

  17. Viral and atypical bacterial infections in the outpatient pediatric cystic fibrosis clinic

    DEFF Research Database (Denmark)

    Olesen, Hanne Vebert; Nielsen, Lars P; Schiotz, Peter Oluf

    2006-01-01

    BACKGROUND: Respiratory viral and atypical bacterial infections are associated with pulmonary exacerbations and hospitalisations in cystic fibrosis patients. We wanted to study the impact of such infections on children attending the outpatient clinic. METHODS: Seventy-five children were followed...

  18. The natural history of HIV infection

    DEFF Research Database (Denmark)

    Sabin, C.A.; Lundgren, J.D.

    2013-01-01

    PURPOSE OF REVIEW: To review recent published literature around three areas: long-term nonprogression/viral control; predictors of viral load set point/disease progression; and the potential impact of antiretroviral therapy (ART) in early HIV infection. RECENT FINDINGS: The natural course...... of untreated HIV infection varies widely with some HIV-positive individuals able to maintain high CD4 cell counts and/or suppressed viral load in the absence of ART. Although similar, the underlying mechanistic processes leading to long-term nonprogression and viral control are likely to differ. Concerted...... the immunological deterioration which would otherwise be seen in untreated HIV infection, recent studies do not address the longer term clinical benefits of ART at this very early stage. SUMMARY: A better understanding of the relative influences of viral, host, and environmental factors on the natural course of HIV...

  19. A Rapid Blood Test To Determine the Active Status and Duration of Acute Viral Infection.

    Science.gov (United States)

    Zheng, Tianyu; Finn, Caroline; Parrett, Christopher J; Dhume, Kunal; Hwang, Ji Hae; Sidhom, David; Strutt, Tara M; Li Sip, Yuen Yee; McKinstry, Karl K; Huo, Qun

    2017-11-10

    The ability to rapidly detect and diagnose acute viral infections is crucial for infectious disease control and management. Serology testing for the presence of virus-elicited antibodies in blood is one of the methods used commonly for clinical diagnosis of viral infections. However, standard serology-based tests have a significant limitation: they cannot easily distinguish active from past, historical infections. As a result, it is difficult to determine whether a patient is currently infected with a virus or not, and on an optimal course of action, based off of positive serology testing responses. Here, we report a nanoparticle-enabled blood test that can help overcome this major challenge. The new test is based on the analysis of virus-elicited immunoglobulin G (IgG) antibody present in the protein corona of a gold nanoparticle surface upon mixing the gold nanoparticles with blood sera. Studies conducted on mouse models of influenza A virus infection show that the test gives positive responses only in the presence of a recent acute viral infection, approximately between day 14 and day 21 following the infection, and becomes negative thereafter. When used together with the traditional serology testing, the nanoparticle test can determine clearly whether a positive serology response is due to a recent or historical viral infection. This new blood test can provide critical clinical information needed to optimize further treatment and/or to determine if further quarantining should be continued.

  20. Pseudothrombocytopenia or platelet clumping as a possible cause of low platelet count in patients with viral infection: a case series from single institution focusing on hepatitis A virus infection.

    Science.gov (United States)

    Choe, W-H; Cho, Y-U; Chae, J-D; Kim, S-H

    2013-02-01

    Pseudothrombocytopenia (PTCP) is the phenomenon of ethylenediaminetetraacetic acid anticoagulant-activated platelet clumping, which results in artificially low platelet counts. Other investigators have reported a few cases of PTCP associated with viral infections. The objective of this study was to demonstrate the association of viral infection with PTCP. Medical records of patients with thrombocytopenia who were tested for peripheral blood smear examination between March 2009 and February 2011 were reviewed for platelet clumping and viral infection. Thrombocytopenic patients with viral infection had a higher frequency of platelet clumping than those with other diseases, which was statistically significant (13.8% vs. 6.5%, respectively: P = 0.003). Among the 18 cases where PTCP or platelet clumping was related to viral infection, hepatitis A virus infection (72.2%) was most common, followed by cytomegalovirus (11.1%) and influenza A H1N1 infections (5.6%). A third (33.3%) of the patients had platelet counts viral infection, particularly if the platelet count is unexpectedly low, because failure to recognize PTCP may lead to unnecessary diagnostic tests and patient mismanagement. © 2012 Blackwell Publishing Ltd.

  1. Viral infections as potential triggers of type 1 diabetes

    NARCIS (Netherlands)

    van der Werf, Nienke; Kroese, Frans G. M.; Rozing, Jan; Hillebrands, Jan-Luuk

    During the last decades, the incidence of type 1 diabetes (T1D) has increased significantly, reaching percentages of 3% annually worldwide. This increase suggests that besides genetical factors environmental perturbations (including viral infections) are also involved in the pathogenesis of T1D. T1D

  2. Bombyx mori nucleopolyhedrovirus ORF54, a viral desmoplakin gene, is associated with the infectivity of budded virions.

    Science.gov (United States)

    Zhang, Min-Juan; Tian, Cai-Hong; Fan, Xiao-Ying; Lou, Yi-Han; Cheng, Ruo-Lin; Zhang, Chuan-Xi

    2012-07-01

    Bombyx mori nucleopolyhedrovirus (BmNPV) ORF54 (Bm54), a member of the viral desmoplakin N-terminus superfamily, is homologous to Autographa californica nucleopolyhedrovirus (AcMNPV) ORF66, which is required for the efficient egress of nucleocapsids from the nucleus and occlusion body formation. In this paper, we generated a bacmid with the Bm54 gene deleted via homologous recombination in Escherichia coli and characterized the mutant virus using a transfection-infection assay and transmission electron microscopy analysis. Our results demonstrated that the cells transfected with viral DNA lacking Bm54 produced non-infectious budded viruses (BVs). Electron microscopy showed that although the deletion of Bm54 did not affect assembly and release of nucleocapsids, it severely affected polyhedron formation. In conclusion, deletion of Bm54 resulted in non-infectious BV and defective polyhedra. Although the sequences of Bm54 and Ac66 are very similar, the two genes function quite differently in the regulation of viral life cycle.

  3. 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

  4. Évolution De La Prevalence Des Infections Virales Transmissibles ...

    African Journals Online (AJOL)

    Évolution De La Prevalence Des Infections Virales Transmissibles Par Transfusion Chez Les Donneurs De Sang Du Cnts De Cote D'ivoire De 2000 A 2010. B Dembélé, KA Inwoley, MK Diane, R Affi-Aboli, AS Abisse, BL Siransy, S Konate, AS Oga, D Sawadogo ...

  5. Establishment of human papillomavirus infection requires cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Dohun Pyeon

    2009-02-01

    Full Text Available Human papillomaviruses (HPVs are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, such as vaccines and microbicides, to prevent HPV infections. Developing the latter requires a better understanding of the infectious life cycle of HPVs. The HPV infectious life cycle is closely linked to the differentiation state of the stratified epithelium it infects, with progeny virus only made in the terminally differentiating suprabasal compartment. It has long been recognized that HPV must first establish its infection within the basal layer of stratified epithelium, but why this is the case has not been understood. In part this restriction might reflect specificity of expression of entry receptors. However, this hypothesis could not fully explain the differentiation restriction of HPV infection, since many cell types can be infected with HPVs in monolayer cell culture. Here, we used chemical biology approaches to reveal that cell cycle progression through mitosis is critical for HPV infection. Using infectious HPV16 particles containing the intact viral genome, G1-synchronized human keratinocytes as hosts, and early viral gene expression as a readout for infection, we learned that the recipient cell must enter M phase (mitosis for HPV infection to take place. Late M phase inhibitors had no effect on infection, whereas G1, S, G2, and early M phase cell cycle inhibitors efficiently prevented infection. We conclude that host cells need to pass through early prophase for successful onset of transcription of the HPV encapsidated genes. These findings provide one reason why HPVs initially establish infections in the basal compartment of stratified epithelia. Only this compartment of the epithelium contains cells progressing through the cell cycle, and therefore it is only in these cells that HPVs can establish their infection. By defining a major condition for cell susceptibility to HPV infection, these

  6. Zoonotic Viral Deseases and Virus Discovery

    DEFF Research Database (Denmark)

    Nielsen, Sandra Cathrine Abel

    Viruses are the most abundant organisms on earth and are ubiquitous in all environments where life is present. They are capable of infecting all cellular forms of life, sometimes causing disease in the infected host. This thesis is broadly divided into two main sections with three projects...... program of wildlife, and with the purpose of preventing the next disease emerging from these animals. Numerous viruses were detected of which many were novel variants, thus reaffirming the notion that attention should be focused at these animals. Near-complete viral genome sequencing was performed...

  7. A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China.

    Science.gov (United States)

    He, Ying; Lin, Guang-Yu; Wang, Qiong; Cai, Xiao-Ying; Zhang, Yin-Hui; Lin, Chuang-Xing; Lu, Chang-Dong; Lu, Xue-Dong

    2014-07-01

    The epidemiology of local viral etiologies is essential for the management of viral respiratory tract infections. Limited data are available in China to describe the epidemiology of viral respiratory infections, especially in small-medium cities and rural areas. To determine the viral etiology and seasonality of acute respiratory infections in hospitalized children, a 3-year study was conducted in Shenzhen, China. Nasopharyngeal aspirates from eligible children were collected. Influenza and other respiratory viruses were tested by molecular assays simultaneously. Data were analyzed to describe the frequency and seasonality. Of the 2025 children enrolled in the study, 971 (48.0%) were positive for at least one viral pathogen, in which 890 (91.7%) were respiratory syncytial virus (RSV; 30.5%) and human rhinovirus (HRV; 21.5%). Co-infections were found in 302 cases (31.1%), and dual viral infection was dominant. RSV, HRV and IAV were the most frequent viral agents involved in co-infection. On the whole, the obvious seasonal peaks mainly from March to May were observed with peak strength varying from 1 year to another. This study provides a basic profile of the epidemiology of acute respiratory viral infection in hospitalized children in Shenzhen. The spectrum of viruses in the study site is similar to that in other places, but the seasonality is closely related to geographic position, different from that in big cities in northern China and neighboring Hong Kong. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  8. The impact of transient combination antiretroviral treatment in early HIV infection on viral suppression and immunologic response in later treatment.

    Science.gov (United States)

    Pantazis, Nikos; Touloumi, Giota; Meyer, Laurence; Olson, Ashley; Costagliola, Dominique; Kelleher, Anthony D; Lutsar, Irja; Chaix, Marie-Laure; Fisher, Martin; Moreno, Santiago; Porter, Kholoud

    2016-03-27

    Effects of transient combination antiretroviral treatment (cART) initiated during early HIV infection (EHI) remain unclear. We investigate whether this intervention affects viral suppression and CD4 cell count increase following its reinitiation in chronic infection (CHI). Longitudinal observational study. We identified adult patients from Concerted Action of Seroconversion to AIDS and Death in Europe who seroconverted after 1/1/2000, had a 12 months or less HIV test interval and initiated cART from naive. We classified individuals as 'pretreated in EHI' if treated within 6 months of seroconversion, interrupted for at least 12 weeks, and reinitiated during CHI. Statistical analysis was performed using survival analysis methods and mixed models. Pretreated and initiated in CHI groups comprised 202 and 4263 individuals, with median follow-up after CHI treatment 4.5 and 3 years, respectively. Both groups had similar virologic response and relapse rates (P = 0.585 and P = 0.206) but pretreated individuals restarted treatment with higher baseline CD4 cell count (∼80 cells/μl; P treatment (re)initiation. Assuming common baseline CD4 cell count, differences in CD4 cell count slopes were nonsignificant. Immunovirologic response to CHI treatment was not associated with timing or duration of the transient treatment. Although treatment interruptions are not recommended, stopping cART initiated in EHI does not seem to reduce the chance of a successful outcome of treatment in CHI.

  9. Lack of viral selection in human immunodeficiency virus type 1 mother-to-child transmission with primary infection during late pregnancy and/or breastfeeding.

    Science.gov (United States)

    Ceballos, Ana; Andreani, Guadalupe; Ripamonti, Chiara; Dilernia, Dario; Mendez, Ramiro; Rabinovich, Roberto D; Cárdenas, Patricia Coll; Zala, Carlos; Cahn, Pedro; Scarlatti, Gabriella; Martínez Peralta, Liliana

    2008-11-01

    Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) as described for women with an established infection is, in most cases, associated with the transmission of few maternal variants. This study analysed virus variability in four cases of maternal primary infection occurring during pregnancy and/or breastfeeding. Estimated time of seroconversion was at 4 months of pregnancy for one woman (early seroconversion) and during the last months of pregnancy and/or breastfeeding for the remaining three (late seroconversion). The C2V3 envelope region was analysed in samples of mother-child pairs by molecular cloning and sequencing. Comparisons of nucleotide and amino acid sequences as well as phylogenetic analysis were performed. The results showed low variability in the virus population of both mother and child. Maximum-likelihood analysis showed that, in the early pregnancy seroconversion case, a minor viral variant with further evolution in the child was transmitted, which could indicate a selection event in MTCT or a stochastic event, whereas in the late seroconversion cases, the mother's and child's sequences were intermingled, which is compatible with the transmission of multiple viral variants from the mother's major population. These results could be explained by the less pronounced selective pressure exerted by the immune system in the early stages of the mother's infection, which could play a role in MTCT of HIV-1.

  10. Pharyngitis - viral

    Science.gov (United States)

    ... throat is due to a viral infection. The antibiotics will not help. Using them to treat viral infections helps bacteria become resistant to antibiotics. With some sore throats (such as those caused ...

  11. Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.

    Science.gov (United States)

    Ferns, R Bridget; Tarr, Alexander W; Hue, Stephane; Urbanowicz, Richard A; McClure, C Patrick; Gilson, Richard; Ball, Jonathan K; Nastouli, Eleni; Garson, Jeremy A; Pillay, Deenan

    2016-05-01

    HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village

    Directory of Open Access Journals (Sweden)

    Ricard Dominique

    2010-05-01

    Full Text Available Abstract Background There have been no previous studies of the long-term survival and temporal changes in plasma viral load among HIV-2 infected subjects. Methods 133 HIV-2 infected and 158 HIV-uninfected subjects from a rural area in North-west Guinea-Bissau, West Africa were enrolled into a prospective cohort study in 1991 and followed-up to mid-2009. Data were collected on four occasions during that period on HIV antibodies, CD4% and HIV-2 plasma viral load. Results Median age (interquartile range [IQR] of HIV-2 infected subjects at time of enrollment was 47 (36, 60 years, similar to that of HIV-uninfected control subjects, 49 (38, 62 (p = 0.4. Median (IQR plasma viral load and CD4 percentage were 347 (50, 4,300 copies/ml and 29 (22, 35 respectively. Overall loss to follow-up to assess vital status was small, at 6.7% and 6.3% for HIV-2 infected and uninfected subjects respectively. An additional 17 (12.8% and 16 (10.1% of HIV-2 infected and uninfected subjects respectively were censored during follow-up due to infection with HIV-1. The mortality rate per 100 person-years (95% CI was 4.5 (3.6, 5.8 among HIV-2 infected subjects compared to 2.1 (1.6, 2.9 among HIV-uninfected (age-sex adjusted rate ratio 1.9 (1.3, 2.8, p Viral load measurements were available for 98%, 78%, 77% and 61% HIV-2 infected subjects who were alive and had not become super-infected with HIV-1, in 1991, 1996, 2003 and 2006 respectively. Median plasma viral load (RNA copies per ml (IQR did not change significantly over time, being 150 (50, 1,554; n = 77 in 1996, 203 (50, 2,837; n = 47 in 2003 and 171 (50, 497; n = 31 in 2006. Thirty seven percent of HIV-2 subjects had undetectable viraemia ( Conclusions A substantial proportion of HIV-2 infected subjects in this cohort have stable plasma viral load, and those with an undetectable viral load (37% at study entry had a normal survival rate. However, the sequential laboratory findings need to be interpreted with caution given

  13. Complexities in Isolation and Purification of Multiple Viruses from Mixed Viral Infections: Viral Interference, Persistence and Exclusion.

    Directory of Open Access Journals (Sweden)

    Naveen Kumar

    Full Text Available Successful purification of multiple viruses from mixed infections remains a challenge. In this study, we investigated peste des petits ruminants virus (PPRV and foot-and-mouth disease virus (FMDV mixed infection in goats. Rather than in a single cell type, cytopathic effect (CPE of the virus was observed in cocultured Vero/BHK-21 cells at 6th blind passage (BP. PPRV, but not FMDV could be purified from the virus mixture by plaque assay. Viral RNA (mixture transfection in BHK-21 cells produced FMDV but not PPRV virions, a strategy which we have successfully employed for the first time to eliminate the negative-stranded RNA virus from the virus mixture. FMDV phenotypes, such as replication competent but noncytolytic, cytolytic but defective in plaque formation and, cytolytic but defective in both plaque formation and standard FMDV genome were observed respectively, at passage level BP8, BP15 and BP19 and hence complicated virus isolation in the cell culture system. Mixed infection was not found to induce any significant antigenic and genetic diversity in both PPRV and FMDV. Further, we for the first time demonstrated the viral interference between PPRV and FMDV. Prior transfection of PPRV RNA, but not Newcastle disease virus (NDV and rotavirus RNA resulted in reduced FMDV replication in BHK-21 cells suggesting that the PPRV RNA-induced interference was specifically directed against FMDV. On long-term coinfection of some acute pathogenic viruses (all possible combinations of PPRV, FMDV, NDV and buffalopox virus in Vero cells, in most cases, one of the coinfecting viruses was excluded at passage level 5 suggesting that the long-term coinfection may modify viral persistence. To the best of our knowledge, this is the first documented evidence describing a natural mixed infection of FMDV and PPRV. The study not only provides simple and reliable methodologies for isolation and purification of two epidemiologically and economically important groups of

  14. Transmission of clonal hepatitis C virus genomes reveals the dominant but transitory role of CD8¿ T cells in early viral evolution

    DEFF Research Database (Denmark)

    Callendret, Benoît; Bukh, Jens; Eccleston, Heather B

    2011-01-01

    occurred slowly over several years of chronic infection. Together these observations indicate that during acute hepatitis C, virus evolution was driven primarily by positive selection pressure exerted by CD8(+) T cells. This influence of immune pressure on viral evolution appears to subside as chronic......The RNA genome of the hepatitis C virus (HCV) diversifies rapidly during the acute phase of infection, but the selective forces that drive this process remain poorly defined. Here we examined whether Darwinian selection pressure imposed by CD8(+) T cells is a dominant force driving early amino acid...... replacement in HCV viral populations. This question was addressed in two chimpanzees followed for 8 to 10 years after infection with a well-defined inoculum composed of a clonal genotype 1a (isolate H77C) HCV genome. Detailed characterization of CD8(+) T cell responses combined with sequencing of recovered...

  15. Rapid host immune response and viral dynamics in herpes simplex virus-2 infection

    Science.gov (United States)

    Schiffer, Joshua T; Corey, Lawrence

    2014-01-01

    Herpes Simplex Virus-2 (HSV-2) is episodically shed throughout the human genital tract. While high viral load correlates with development of genital ulcers, shedding also commonly occurs even when ulcers are not present, allowing for silent transmission during coitus and contributing to high seroprevalence of HSV-2 worldwide. Frequent viral reactivation occurs despite diverse and complementary host and viral mechanisms within ganglionic tissue that predispose towards latency, suggesting that viral replication may be constantly occurring in a small minority of neurons within the ganglia. Within genital mucosa, the in vivo expansion and clearance rates of HSV-2 are extremely rapid. Resident dendritic cells and memory HSV-specific T cells persist at prior sites of genital tract reactivation, and in conjunction with prompt innate recognition of infected cells, lead to rapid containment of infected cells. Shedding episodes vary greatly in duration and severity within a single person over time: this heterogeneity appears best explained by variation in the densities of host immunity across the genital tract. The fact that immune responses usually control viral replication in genital skin prior to development of lesions provides optimism that enhancing such responses could lead to effective vaccines and immunotherapies. PMID:23467247

  16. Protective Effect of Surfactant Protein D in Pulmonary Vaccinia Virus Infection: Implication of A27 Viral Protein

    Directory of Open Access Journals (Sweden)

    Julien Perino

    2013-03-01

    Full Text Available Vaccinia virus (VACV was used as a surrogate of variola virus (VARV (genus Orthopoxvirus, the causative agent of smallpox, to study Orthopoxvirus infection. VARV is principally transmitted between humans by aerosol droplets. Once inhaled, VARV first infects the respiratory tract where it could encounter surfactant components, such as soluble pattern recognition receptors. Surfactant protein D (SP-D, constitutively present in the lining fluids of the respiratory tract, plays important roles in innate host defense against virus infection. We investigated the role of SP-D in VACV infection and studied the A27 viral protein involvement in the interaction with SP-D. Interaction between SP-D and VACV caused viral inhibition in a lung cell model. Interaction of SP-D with VACV was mediated by the A27 viral protein. Binding required Ca2+ and interactions were blocked in the presence of excess of SP-D saccharide ligands. A27, which lacks glycosylation, directly interacted with SP-D. The interaction between SP-D and the viral particle was also observed using electron microscopy. Infection of mice lacking SP-D (SP-D-/- resulted in increased mortality compared to SP-D+/+ mice. Altogether, our data show that SP-D participates in host defense against the vaccinia virus infection and that the interaction occurs with the viral surface protein A27.

  17. Diagnostic value of meat juice in early detection of classical swine fever infection

    DEFF Research Database (Denmark)

    Lohse, Louise; Uttenthal, Åse; Rasmussen, Thomas Bruun

    2011-01-01

    samples originated from pigs infected with low virulence CSFV strains and/or when samples were collected within the first days after infection. In conclusion, while not the first choice for sample material for CSFV diagnosis, meat juice may constitute a useful alternative for herd-based studies or when......To evaluate the diagnostic potential of meat juice for early detection of Classical swine fever virus (CSFV), meat juice and serum samples from pigs experimentally infected with different strains of CSFV were compared for virus load. From all samples, viral RNA was extracted by automated procedure...... blood and/or target organ material is not available. Strain virulence and time points for sample collection after infection are factors of importance for diagnostic success....

  18. Viral Reservoirs in Lymph Nodes of FIV-Infected Progressor and Long-Term Non-Progressor Cats during the Asymptomatic Phase.

    Directory of Open Access Journals (Sweden)

    C D Eckstrand

    Full Text Available Examination of a cohort of cats experimentally infected with feline immunodeficiency virus (FIV for 5.75 years revealed detectable proviral DNA in peripheral blood mononuclear cells (PBMCs harvested during the asymptomatic phase, undetectable plasma viral RNA (FIV gag, and rarely detectable cell-associated viral RNA. Despite apparent viral latency in peripheral CD4+ T cells, circulating CD4+ T cell numbers progressively declined in progressor animals. The aim of this study was to explore this dichotomy of peripheral blood viral latency in the face of progressive immunopathology. The viral replication status, cellular immunophenotypes, and histopathologic features were compared between popliteal lymph nodes (PLNs and peripheral blood. Also, we identified and further characterized one of the FIV-infected cats identified as a long-term non-progressor (LTNP.PLN-derived leukocytes from FIV-infected cats during the chronic asymptomatic phase demonstrated active viral gag transcription and FIV protein translation as determined by real-time RT-PCR, Western blot and in situ immunohistochemistry, whereas viral RNA in blood leukocytes was either undetectable or intermittently detectable and viral protein was not detected. Active transcription of viral RNA was detectable in PLN-derived CD4+ and CD21+ leukocytes. Replication competent provirus was reactivated ex vivo from PLN-derived leukocytes from three of four FIV-infected cats. Progressor cats showed a persistent and dramatically decreased proportion and absolute count of CD4+ T cells in blood, and a decreased proportion of CD4+ T cells in PLNs. A single long-term non-progressor (LTNP cat persistently demonstrated an absolute peripheral blood CD4+ T cell count indistinguishable from uninfected animals, a lower proviral load in unfractionated blood and PLN leukocytes, and very low amounts of viral RNA in the PLN.Collectively our data indicates that PLNs harbor important reservoirs of ongoing viral

  19. Reading the viral signature by Toll-like receptors and other pattern recognition receptors.

    Science.gov (United States)

    Mogensen, Trine H; Paludan, Søren R

    2005-03-01

    Successful host defense against viral infections relies on early production of type I interferon (IFN) and subsequent activation of a cellular cytotoxic response. The acute IFN and inflammatory response against virus infections is mediated by cellular pattern-recognition receptors (PRRs) that recognize specific molecular structures on viral particles or products of viral replication. Toll-like receptors (TLRs) constitute a class of membrane-bound PRRs capable of detecting microbial infections. While TLR2 and TLR4, which were first identified to recognize Gram-positive and Gram-negative bacteria, respectively, sense specific viral proteins on the cell surface, TLRs 3, 7, 8, and 9 serve as receptors for viral nucleic acids in endosomic compartments. In addition to TLRs, cells express cytoplasmic PRRs such as the RNA helicase retinoic acid inducible gene I and the kinase double-stranded RNA-activated protein kinase R, both of which sense dsRNA, a characteristic signature of viral replication, and initiate a protective cellular response. Here we review the recent progress in our understanding of PRRs and viral infections and discuss the molecular and cellular responses evoked by virus-activated PRRs. Finally, we look into what is currently known about the role of PRRs in viral infections in vivo.

  20. Innate immune responses of calves during transient infection with a noncytopathic strain of bovine viral diarrhea virus

    DEFF Research Database (Denmark)

    Muller-Doblies, D.; Arquint, A.; Schaller, P.

    2004-01-01

    In this study, six immunocompetent calves were experimentally infected with a noncytopathic strain of bovine viral diarrhea virus (BVDV), and the effects of the viral infection on parameters of the innate immune response of the host were analyzed. Clinical and virological data were compared...

  1. Targeting the IL-33/IL-13 Axis for Respiratory Viral Infections.

    Science.gov (United States)

    Donovan, Chantal; Bourke, Jane E; Vlahos, Ross

    2016-04-01

    Lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are highly prevalent worldwide. One of the major factors that limits the efficacy of current medication in these patients are viral infections, leading to exacerbations of symptoms and decreased quality of life. Current pharmacological strategies targeting virus-induced lung disease are problematic due to antiviral resistance and the requirement for strain-specific vaccination. Thus, new therapeutic strategies are urgently required. In this Opinion article, we provide state-of-the-art evidence from humans and preclinical animal models implicating the interleukin (IL)-33/IL-13 axis in virus-induced lung disease. Thus, targeting the IL-33/IL-13 axis may be a feasible way to overcome the limitations of current therapy used to treat virus-induced exacerbations of lung disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. A simulation framework to investigate in vitro viral infection dynamics

    NARCIS (Netherlands)

    Bankhead, A.; Mancini, E.; Sims, A.C.; Baric, R.S.; McWeeney, S.; Sloot, P.M.A.

    2013-01-01

    Virus infection is a complex biological phenomenon for which in vitro experiments provide a uniquely concise view where data is often obtained from a single population of cells, under controlled environmental conditions. Nonetheless, data interpretation and real understanding of viral dynamics is

  3. Skin Microvascular Thrombosis in Fusarium Infection in Two Early Biopsied Cases

    Directory of Open Access Journals (Sweden)

    Yang Fan

    2010-05-01

    Full Text Available Fusarium species cause rare and severe infections. Their incidence is increasing in immunocompromised patients but they are also observed in healthy hosts. Because of the rapid dissemination of infection and the frequent resistance of Fusarium species to antifungal drugs, histopathologic evidence of hyphae is very helpful to obtain the diagnosis rapidly. We report the clinical and pathological features of two patients with initial cutaneous lesions. Cutaneous early biopsies showed microvessel involvement with hyphae and thrombosis. Fusarium infection was confirmed by skin culture. Hyphae within a microvessel thrombus in the skin were highly suggestive of disseminated fungal infection. These pathological features enabled to establish an early diagnosis and to start efficient antifungal treatment. In early cutaneous biopsies of immunocompromised patients, the presence of cutaneous vessel thrombosis can suggest a fungal infection and may help to start specific therapy without delay for these life-threatening infections.

  4. Parallel epigenomic and transcriptomic responses to viral infection in honey bees (Apis mellifera).

    Science.gov (United States)

    Galbraith, David A; Yang, Xingyu; Niño, Elina Lastro; Yi, Soojin; Grozinger, Christina

    2015-03-01

    Populations of honey bees are declining throughout the world, with US beekeepers losing 30% of their colonies each winter. Though multiple factors are driving these colony losses, it is increasingly clear that viruses play a major role. However, information about the molecular mechanisms mediating antiviral immunity in honey bees is surprisingly limited. Here, we examined the transcriptional and epigenetic (DNA methylation) responses to viral infection in honey bee workers. One-day old worker honey bees were fed solutions containing Israeli Acute Paralysis Virus (IAPV), a virus which causes muscle paralysis and death and has previously been associated with colony loss. Uninfected control and infected, symptomatic bees were collected within 20-24 hours after infection. Worker fat bodies, the primary tissue involved in metabolism, detoxification and immune responses, were collected for analysis. We performed transcriptome- and bisulfite-sequencing of the worker fat bodies to identify genome-wide gene expression and DNA methylation patterns associated with viral infection. There were 753 differentially expressed genes (FDR<0.05) in infected versus control bees, including several genes involved in epigenetic and antiviral pathways. DNA methylation status of 156 genes (FDR<0.1) changed significantly as a result of the infection, including those involved in antiviral responses in humans. There was no significant overlap between the significantly differentially expressed and significantly differentially methylated genes, and indeed, the genomic characteristics of these sets of genes were quite distinct. Our results indicate that honey bees have two distinct molecular pathways, mediated by transcription and methylation, that modulate protein levels and/or function in response to viral infections.

  5. Parallel epigenomic and transcriptomic responses to viral infection in honey bees (Apis mellifera.

    Directory of Open Access Journals (Sweden)

    David A Galbraith

    2015-03-01

    Full Text Available Populations of honey bees are declining throughout the world, with US beekeepers losing 30% of their colonies each winter. Though multiple factors are driving these colony losses, it is increasingly clear that viruses play a major role. However, information about the molecular mechanisms mediating antiviral immunity in honey bees is surprisingly limited. Here, we examined the transcriptional and epigenetic (DNA methylation responses to viral infection in honey bee workers. One-day old worker honey bees were fed solutions containing Israeli Acute Paralysis Virus (IAPV, a virus which causes muscle paralysis and death and has previously been associated with colony loss. Uninfected control and infected, symptomatic bees were collected within 20-24 hours after infection. Worker fat bodies, the primary tissue involved in metabolism, detoxification and immune responses, were collected for analysis. We performed transcriptome- and bisulfite-sequencing of the worker fat bodies to identify genome-wide gene expression and DNA methylation patterns associated with viral infection. There were 753 differentially expressed genes (FDR<0.05 in infected versus control bees, including several genes involved in epigenetic and antiviral pathways. DNA methylation status of 156 genes (FDR<0.1 changed significantly as a result of the infection, including those involved in antiviral responses in humans. There was no significant overlap between the significantly differentially expressed and significantly differentially methylated genes, and indeed, the genomic characteristics of these sets of genes were quite distinct. Our results indicate that honey bees have two distinct molecular pathways, mediated by transcription and methylation, that modulate protein levels and/or function in response to viral infections.

  6. Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment.

    Science.gov (United States)

    Baroncelli, Silvia; Pirillo, Maria F; Tamburrini, Enrica; Guaraldi, Giovanni; Pinnetti, Carmela; Degli Antoni, Anna; Galluzzo, Clementina M; Stentarelli, Chiara; Amici, Roberta; Floridia, Marco

    2015-07-01

    There is limited information on full viral suppression and low-level HIV-RNA viremia in HIV-infected women at the end of pregnancy. We investigated HIV-RNA levels close to delivery in women on antiretroviral treatment in order to define rates of complete suppression, low-level viremia, and quantifiable HIV-RNA, exploring as potential determinants some clinical and viroimmunological variables. Plasma samples from a national study in Italy, collected between 2003 and 2012, were used. According to plasma HIV-RNA levels, three groups were defined: full suppression (target not detected), low-level viremia (target detected but HIV-RNA (≥37 copies/ml). Multivariable logistic regression was used to define determinants of full viral suppression and of quantifiable HIV-RNA. Among 107 women evaluated at a median gestational age of 35 weeks, 90 (84.1%) had HIV-RNA HIV-RNA was 109 copies/ml (IQR 46-251), with only one case showing resistance (mutation M184V; rate: 9.1%). In multivariable analyses, women with higher baseline HIV-RNA levels and with hepatitis C virus (HCV) coinfection were significantly more likely to have quantifiable HIV-RNA in late pregnancy. Full viral suppression was significantly more likely with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens and significantly less likely with higher HIV-RNA in early pregnancy. No cases of HIV transmission occurred. In conclusion, HIV-infected pregnant women showed a high rate of viral suppression and a low resistance rate before delivery. In most cases no target HIV-RNA was detected in plasma, suggesting a low risk of subsequent virological rebound and development of resistance. Women with high levels of HIV-RNA in early pregnancy and those who have concomitant HCV infection should be considered at higher risk of having quantifiable HIV-RNA at the end of pregnancy.

  7. ANTI-VIRAL ACTIVITY OF GLYCIRRHETINIC AND GLYCIRRHIZIC ACIDS

    Directory of Open Access Journals (Sweden)

    V. V. Zarubaev

    2016-01-01

    Full Text Available Influenza is a highly contagious human disease. In the course of use of antiviral drugs drug-resistant strains of the virus are formed, resulting in reduced efficiency of the chemotherapy. The review describes the biological activity of glycirrhetinic (GLA and glycirrhizic (GA acids in terms of their use as a therapeutic agent for viral infections. So, these compounds are against a broad spectrum of viruses, including herpes, corona-, alphaand flaviviruses, human immunodeficiency virus, vaccinia virus, poliovirus type I, vesicular stomatitis virus and influenza A virus. These data indicate that anti-viral effect of these compounds is due to several types of activity — direct antiviral effects, effects on cellular proand anti-viral and immunomodulating pathways, in particular by activation of innate immunity system. GA interferes with early steps of the viral reproductive cycle such as virus binding to its receptor, the absorption of the virus by endocytosis or virus decapsidation in the cytoplasm. This is due to the effect of GA-induced reduction of membrane fluidity. Thus, one mechanism for the antiviral activity of GA is that GA molecule increases the rigidity of cellular and viral membranes after incorporation in there. This results in increasing of energy threshold required for the formation of negative curvature at the fusion zones, as well as difficult lateral migration of the virus-receptor complexes. In addition, glycyrrhizin prevents interaction of viral nucleoprotein with cellular protein HMGB1, which is necessary for the viral life cycle. Glycyrrhizin also inhibits the induction of oxidative stress during influenza infection, exhibiting antioxidant properties, which leads to a reduction of virus-induced production of cytokines/chemokines, without affecting the replication of the virus. A wide spectrum of biological activity and effect on various aspects of the viral pathogenesis substantiate the effect of GA and GLA as a component

  8. The Translesion Polymerase Pol η Is Required for Efficient Epstein-Barr Virus Infectivity and Is Regulated by the Viral Deubiquitinating Enzyme BPLF1.

    Science.gov (United States)

    Dyson, Ossie F; Pagano, Joseph S; Whitehurst, Christopher B

    2017-10-01

    Epstein-Barr virus (EBV) infection and lytic replication are known to induce a cellular DNA damage response. We previously showed that the virally encoded BPLF1 protein interacts with and regulates several members of the translesion synthesis (TLS) pathway, a DNA damage tolerance pathway, and that these cellular factors enhance viral infectivity. BPLF1 is a late lytic cycle gene, but the protein is also packaged in the viral tegument, indicating that BPLF1 may function both early and late during infection. The BPLF1 protein expresses deubiquitinating activity that is strictly conserved across the Herpesviridae ; mutation of the active site cysteine results in a loss of enzymatic activity. Infection with an EBV BPLF1 knockout virus results in decreased EBV infectivity. Polymerase eta (Pol η), a specialized DNA repair polymerase, functions in TLS and allows for DNA replication complexes to bypass lesions in DNA. Here we report that BPLF1 interacts with Pol η and that Pol η protein levels are increased in the presence of functional BPLF1. BPLF1 promotes a nuclear relocalization of Pol η molecules which are focus-like in appearance, consistent with the localization observed when Pol η is recruited to sites of DNA damage. Knockdown of Pol η resulted in decreased production of infectious virus, and further, Pol η was found to bind to EBV DNA, suggesting that it may allow for bypass of damaged viral DNA during its replication. The results suggest a mechanism by which EBV recruits cellular repair factors, such as Pol η, to sites of viral DNA damage via BPLF1, thereby allowing for efficient viral DNA replication. IMPORTANCE Epstein-Barr virus is the causative agent of infectious mononucleosis and infects approximately 90% of the world's population. It causes lymphomas in individuals with acquired and innate immune disorders and is strongly associated with Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B-cell lymphomas, nasopharyngeal carcinoma (NPC), and

  9. Foxp3+ regulatory T cells control persistence of viral CNS infection.

    Directory of Open Access Journals (Sweden)

    Dajana Reuter

    Full Text Available We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified mice and recombinant measles virus (MV. Using this model infection we investigated the role of regulatory T cells (Tregs as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4(+ CD25(+ Foxp3(+ Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8(+ T cells predominantly recognising the H-2D(b-presented viral hemagglutinin epitope MV-H(22-30 (RIVINREHL were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p. application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT in DEREG (depletion of regulatory T cells-mice induced an increase of virus-specific CD8(+ effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.

  10. Characterization of viroplasm formation during the early stages of rotavirus infection

    Directory of Open Access Journals (Sweden)

    Isa Pavel

    2010-11-01

    Full Text Available Abstract Background During rotavirus replication cycle, electron-dense cytoplasmic inclusions named viroplasms are formed, and two non-structural proteins, NSP2 and NSP5, have been shown to localize in these membrane-free structures. In these inclusions, replication of dsRNA and packaging of pre-virion particles occur. Despite the importance of viroplasms in the replication cycle of rotavirus, the information regarding their formation, and the possible sites of their nucleation during the early stages of infection is scarce. Here, we analyzed the formation of viroplasms after infection of MA104 cells with the rotavirus strain RRV, using different multiplicities of infection (MOI, and different times post-infection. The possibility that viroplasms formation is nucleated by the entering viral particles was investigated using fluorescently labeled purified rotavirus particles. Results The immunofluorescent detection of viroplasms, using antibodies specific to NSP2 showed that both the number and size of viroplasms increased during infection, and depend on the MOI used. Small-size viroplasms predominated independently of the MOI or time post-infection, although at MOI's of 2.5 and 10 the proportion of larger viroplasms increased. Purified RRV particles were successfully labeled with the Cy5 mono reactive dye, without decrease in virus infectivity, and the labeled viruses were clearly observed by confocal microscope. PAGE gel analysis showed that most viral proteins were labeled; including the intermediate capsid protein VP6. Only 2 out of 117 Cy5-labeled virus particles colocalized with newly formed viroplasms at 4 hours post-infection. Conclusions The results presented in this work suggest that during rotavirus infection the number and size of viroplasm increases in an MOI-dependent manner. The Cy5 in vitro labeled virus particles were not found to colocalize with newly formed viroplasms, suggesting that they are not involved in viroplasm

  11. Interferon-alpha mediates restriction of human immunodeficiency virus type-1 replication in primary human macrophages at an early stage of replication.

    Directory of Open Access Journals (Sweden)

    Kelly M Cheney

    2010-10-01

    Full Text Available Type I interferons (IFNα and β are induced directly in response to viral infection, resulting in an antiviral state for the cell. In vitro studies have shown that IFNα is a potent inhibitor of viral replication; however, its role in HIV-1 infection is incompletely understood. In this study we describe the ability of IFNα to restrict HIV-1 infection in primary human macrophages in contrast to peripheral blood mononuclear cells and monocyte-derived dendritic cells. Inhibition to HIV-1 replication in cells pretreated with IFNα occurred at an early stage in the virus life cycle. Late viral events such as budding and subsequent rounds of infection were not affected by IFNα treatment. Analysis of early and late HIV-1 reverse transcripts and integrated proviral DNA confirmed an early post entry role for IFNα. First strand cDNA synthesis was slightly reduced but late and integrated products were severely depleted, suggesting that initiation or the nucleic acid intermediates of reverse transcription are targeted. The depletion of integrated provirus is disproportionally greater than that of viral cDNA synthesis suggesting the possibility of a least an additional later target. A role for either cellular protein APOBEC3G or tetherin in this IFNα mediated restriction has been excluded. Vpu, previously shown by others to rescue a viral budding restriction by tetherin, could not overcome this IFNα induced effect. Determining both the viral determinants and cellular proteins involved may lead to novel therapeutic approaches. Our results add to the understanding of HIV-1 restriction by IFNα.

  12. Quantum virology : improved management of viral infections through quantitative measurements

    NARCIS (Netherlands)

    Kalpoe, Jaijant Satishkumar

    2007-01-01

    Real-time monitoring of PCR has strongly supported the increased diagnostic use of nucleic acid detection assays in clinical virology. Particularly the improvements in the ability to quantify target nucleic acid sequences offer new opportunities in the management of viral infections. Real-time PCR

  13. Prior Virus Exposure Alters the Long-Term Landscape of Viral Replication during Feline Lentiviral Infection

    Directory of Open Access Journals (Sweden)

    Sue VandeWoude

    2011-10-01

    Full Text Available We developed a feline model of lentiviral cross-species transmission using a puma lentivirus (PLV or FIVPco which infects domestic cats but does not cause disease. Infection with PLV protects cats from CD4+ T-cell decline caused by subsequent infection with virulent feline immunodeficiency virus (FIV. Previous studies implicate innate immune and/or cellular restriction mechanisms for FIV disease attenuation in PLV-infected cats. In this study, we evaluated viral infection and cytokine mRNA transcription in 12 different tissue reservoirs approximately five months post infection. We quantitated tissue proviral load, viral mRNA load and relative transcription of IL-10, IL-12p40 and IFNγ from tissues of cats exposed to FIV, PLV or both viruses and analyzed these parameters using a multivariate statistical approach. The distribution and intensity of FIV infection and IFNγ transcription differed between single and co-infected cats, characterized by higher FIV proviral loads and IFNγ expression in co-infected cat tissues. Variability in FIV mRNA load and IFNγ was significantly more constrained in co-infected versus singly infected cat tissues. Single-infected:co-infected ratios of FIV mRNA load compared to FIV proviral load indicated that active viral transcription was apparently inhibited during co-infection. These results indicate that previous PLV infection increases activation of tissue innate immunity and constrains the ability of FIV to productively infect tissue reservoirs of infection for months, independent of FIV proviral load, supporting a model in which innate immunity and/or modulation of target cell susceptibility play a key role in PLV-induced protection from FIV disease.

  14. How to be good at being a virus : Biochemical constraints of viral life-history evolution

    NARCIS (Netherlands)

    Berngruber, Thomas

    2008-01-01

    Viral reproduction depends on a careful balance of the viral life-cycle in time and magnitude. Maintenance of this balance is granted by the regulation of viral protein production and protein interactions. Viral evolution therefore hinges on the possibilities to optimize these protein interactions.

  15. Profile of HIV-1 RNA viral load among HIV-TB co-infected patients in ...

    African Journals Online (AJOL)

    Profile of HIV-1 RNA viral load among HIV-TB co-infected patients in a tertiary health facility in Maiduguri, Northeastern Nigeria. ... This study aims to estimate the HIV-1 RNA viral load and impact of anti TB therapy (ATT) ... HOW TO USE AJOL.

  16. Viral agents that cause infection through the consumption and handling of food

    International Nuclear Information System (INIS)

    Gomez Murillo, Ileana

    2014-01-01

    Viral agents: Norovirus, Rotavirus, Hepatitis A and E, Nipah virus, highly pathogenic avian influenza and coronavirus that cause the SARS are studied as protagonists in the production of food-borne infectious processes. The most common sources of pollution, viral characteristics that influence the control, routes, methods of detection and prevention of pathogens in food are analyzed. Methodological techniques are investigated to improve early detection of viral pathogens in food, control measures and prevention of food contamination [es

  17. Massive activation of archaeal defense genes during viral infection.

    Science.gov (United States)

    Quax, Tessa E F; Voet, Marleen; Sismeiro, Odile; Dillies, Marie-Agnes; Jagla, Bernd; Coppée, Jean-Yves; Sezonov, Guennadi; Forterre, Patrick; van der Oost, John; Lavigne, Rob; Prangishvili, David

    2013-08-01

    Archaeal viruses display unusually high genetic and morphological diversity. Studies of these viruses proved to be instrumental for the expansion of knowledge on viral diversity and evolution. The Sulfolobus islandicus rod-shaped virus 2 (SIRV2) is a model to study virus-host interactions in Archaea. It is a lytic virus that exploits a unique egress mechanism based on the formation of remarkable pyramidal structures on the host cell envelope. Using whole-transcriptome sequencing, we present here a global map defining host and viral gene expression during the infection cycle of SIRV2 in its hyperthermophilic host S. islandicus LAL14/1. This information was used, in combination with a yeast two-hybrid analysis of SIRV2 protein interactions, to advance current understanding of viral gene functions. As a consequence of SIRV2 infection, transcription of more than one-third of S. islandicus genes was differentially regulated. While expression of genes involved in cell division decreased, those genes playing a role in antiviral defense were activated on a large scale. Expression of genes belonging to toxin-antitoxin and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems was specifically pronounced. The observed different degree of activation of various CRISPR-Cas systems highlights the specialized functions they perform. The information on individual gene expression and activation of antiviral defense systems is expected to aid future studies aimed at detailed understanding of the functions and interplay of these systems in vivo.

  18. Experimental infection of pregnant goats with bovine viral diarrhea virus (BVDV)1 or 2

    Science.gov (United States)

    Infections with bovine viral diarrhea virus (BVDV) of the genus pestivirus, family Flaviviridae, are not limited to cattle but occur in various artiodactyls. Persistently infected (PI) cattle are the main source of BVDV. Persistent infections also occur in heterologous hosts such as sheep and deer. ...

  19. Parvovirus infection-induced DNA damage response

    Science.gov (United States)

    Luo, Yong; Qiu, Jianming

    2014-01-01

    Parvoviruses are a group of small DNA viruses with ssDNA genomes flanked by two inverted terminal structures. Due to a limited genetic resource they require host cellular factors and sometimes a helper virus for efficient viral replication. Recent studies have shown that parvoviruses interact with the DNA damage machinery, which has a significant impact on the life cycle of the virus as well as the fate of infected cells. In addition, due to special DNA structures of the viral genomes, parvoviruses are useful tools for the study of the molecular mechanisms underlying viral infection-induced DNA damage response (DDR). This review aims to summarize recent advances in parvovirus-induced DDR, with a focus on the diverse DDR pathways triggered by different parvoviruses and the consequences of DDR on the viral life cycle as well as the fate of infected cells. PMID:25429305

  20. Evidence of bovine viral diarrhea virus infection in three species of sympatric wild ungulates in Nevada: life history strategies may maintain endemic infections in wild populations

    Directory of Open Access Journals (Sweden)

    Peregrine Lee Wolff

    2016-03-01

    Full Text Available Evidence for bovine viral diarrhea virus (BVDV infection was detected in 2009-10 while investigating a pneumonia die-off in Rocky Mountain bighorn sheep (Ovis canadensis canadensis, and sympatric mountain goats (Oreamnos americanum in adjacent mountain ranges in Elko County, Nevada. Seroprevalence to BVDV-1 was 81% (N=32 in the bighorns and 100% (N=3 in the mountain goats. Serosurveillance from 2011 to 2015 of surviving bighorns and mountain goats as well as sympatric mule deer (Odocoileus hemionus, indicated a prevalence of 72% (N=45, 45% (N=51, and 51% (N=342 respectively. All species had antibody titers to BVDV1 and BVDV2. BVDV1 was isolated in cell culture from three bighorn sheep and a mountain goat kid. BVDV2 was isolated from two mule deer. Six deer (N=96 sampled in 2013 were positive for BVDV by antigen-capture ELISA on ear notch. Wild ungulates and cattle concurrently graze public and private lands in these two mountain ranges, thus providing potential for interspecies viral transmission. Like cattle, mule deer, mountain goats, and bighorn sheep can be infected with BVDV and can develop clinical disease including immunosuppression. Winter migration patterns that increase densities and species interaction during the first and second trimester of gestation may contribute to the long term maintenance of the virus in these wild ungulates. More studies are needed to determine the population level impacts of BVDV infection on these three species.

  1. Interferon-γ Inhibits Ebola Virus Infection.

    Directory of Open Access Journals (Sweden)

    Bethany A Rhein

    Full Text Available Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  2. Interferon-γ Inhibits Ebola Virus Infection.

    Science.gov (United States)

    Rhein, Bethany A; Powers, Linda S; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A; Monick, Martha M; Maury, Wendy

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  3. Long-term follow up of feline leukemia virus infection and characterization of viral RNA loads using molecular methods in tissues of cats with different infection outcomes.

    Science.gov (United States)

    Helfer-Hungerbuehler, A Katrin; Widmer, Stefan; Kessler, Yvonne; Riond, Barbara; Boretti, Felicitas S; Grest, Paula; Lutz, Hans; Hofmann-Lehmann, Regina

    2015-02-02

    It is a remarkable feature for a retrovirus that an infection with feline leukemia virus (FeLV) can result in various outcomes. Whereas some cats contain the infection and show a regressive course, others stay viremic and succumb to the infection within a few years. We hypothesized, that differences in the infection outcome might be causally linked to the viral RNA and provirus loads within the host and these loads therefore may give additional insight into the pathogenesis of the virus. Thus, the goals of the present study were to follow-up on experimentally infected cats and investigate tissues from cats with different infection outcomes using sensitive, specific TaqMan real-time PCR and reverse transcriptase (RT)-PCR. Nineteen experimentally FeLV-A/Glasgow-1-infected cats were categorized into having regressive, progressive or reactivated FeLV infection according to follow-up of FeLV p27 antigen detection in the blood. Remarkably, regressively infected cats showed detectable provirus and viral RNA loads in almost all of the 27 tested tissues, even many years after virus exposure. Moreover, some regressively infected cats reactivated the infection, and these cats had intermediate to high viral RNA and provirus tissue loads. The highest loads were found in viremic cats, independent of their health status. Tissues that represented sites of virus replication and shedding revealed the highest viral RNA and provirus loads, while the lowest loads were present in muscle and nerve tissues. A supplementary analysis of 20 experimentally infected cats with progressive infection revealed a median survival time of 3.1 years (range from 0.6 to 6.5 years); ∼70% (n=14) of these cats developed lymphoma, while leukemia and non-regenerative anemia were observed less frequently. Our results demonstrate that the different infection outcomes are associated with differences in viral RNA and provirus tissue loads. Remarkably, no complete clearance of FeLV viral RNA or provirus was

  4. Persistent infections after natural transmission of bovine viral diarrhoea virus from cattle to goats and among goats

    Science.gov (United States)

    2013-01-01

    Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle worldwide. Infection of a pregnant animal may lead to persistent infection of the foetus and birth of a persistently infected (PI) calf that sheds the virus throughout its life. However, BVD viruses are not strictly species specific. BVDV has been isolated from many domesticated and wild ruminants. This is of practical importance as virus reservoirs in non-bovine hosts may hamper BVDV control in cattle. A goat given as a social companion to a BVDV PI calf gave birth to a PI goat kid. In order to test if goat to goat infections were possible, seronegative pregnant goats were exposed to the PI goat. In parallel, seronegative pregnant goats were kept together with the PI calf. Only the goat to goat transmission resulted in the birth of a next generation of BVDV PI kids whereas all goats kept together with the PI calf aborted. To our knowledge, this is the first report which shows that a PI goat cannot only transmit BVD virus to other goats but that such transmission may indeed lead to the birth of a second generation of PI goats. Genetic analyses indicated that establishment in the new host species may be associated with step-wise adaptations in the viral genome. Thus, goats have the potential to be a reservoir for BVDV. However, the PI goats showed growth retardation and anaemia and their survival under natural conditions remains questionable. PMID:23675947

  5. Persistent infections after natural transmission of bovine viral diarrhoea virus from cattle to goats and among goats.

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    Bachofen, Claudia; Vogt, Hans-Rudolf; Stalder, Hanspeter; Mathys, Tanja; Zanoni, Reto; Hilbe, Monika; Schweizer, Matthias; Peterhans, Ernst

    2013-05-15

    Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle worldwide. Infection of a pregnant animal may lead to persistent infection of the foetus and birth of a persistently infected (PI) calf that sheds the virus throughout its life. However, BVD viruses are not strictly species specific. BVDV has been isolated from many domesticated and wild ruminants. This is of practical importance as virus reservoirs in non-bovine hosts may hamper BVDV control in cattle. A goat given as a social companion to a BVDV PI calf gave birth to a PI goat kid. In order to test if goat to goat infections were possible, seronegative pregnant goats were exposed to the PI goat. In parallel, seronegative pregnant goats were kept together with the PI calf. Only the goat to goat transmission resulted in the birth of a next generation of BVDV PI kids whereas all goats kept together with the PI calf aborted. To our knowledge, this is the first report which shows that a PI goat cannot only transmit BVD virus to other goats but that such transmission may indeed lead to the birth of a second generation of PI goats. Genetic analyses indicated that establishment in the new host species may be associated with step-wise adaptations in the viral genome. Thus, goats have the potential to be a reservoir for BVDV. However, the PI goats showed growth retardation and anaemia and their survival under natural conditions remains questionable.

  6. Genetic Variability of Bovine Viral Diarrhea Virus and Evidence for a Possible Genetic Bottleneck during Vertical Transmission in Persistently Infected Cattle.

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    Natalie Dow

    Full Text Available Bovine viral diarrhea virus (BVDV, a Pestivirus in the family Flaviviridae, is an economically important pathogen of cattle worldwide. The primary propagators of the virus are immunotolerant persistently infected (PI cattle, which shed large quantities of virus throughout life. Despite the absence of an acquired immunity against BVDV in these PI cattle there are strong indications of viral variability that are of clinical and epidemiological importance. In this study the variability of E2 and NS5B sequences in multiple body compartments of PI cattle were characterized using clonal sequencing. Phylogenetic analyses revealed that BVDV exists as a quasispecies within PI cattle. Viral variants were clustered by tissue compartment significantly more often than expected by chance alone with the central nervous system appearing to be a particularly important viral reservoir. We also found strong indications for a genetic bottleneck during vertical transmission from PI animals to their offspring. These quasispecies analyses within PI cattle exemplify the role of the PI host in viral propagation and highlight the complex dynamics of BVDV pathogenesis, transmission and evolution.

  7. Presence of viral RNA and proteins in exosomes from the cellular clones resistant to Rift Valley Fever Virus infection.

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    Noor eAhsan

    2016-02-01

    Full Text Available Rift Valley Fever Virus (RVFV is a RNA virus that belongs to the genus Phlebovirus, family Bunyaviridae. It infects humans and livestock and causes Rift Valley fever. RVFV is considered an agricultural pathogen by the USDA, as it can cause up to 100% abortion in cattle and extensive death of newborns. In addition, it is designated as Category A pathogen by the CDC and the NIAID. In some human cases of RVFV infection, the virus causes fever, ocular damage, liver damage, hemorrhagic fever, and death. There are currently limited options for vaccine candidates, which include the MP-12 and clone 13 versions of RVFV. Viral infections often deregulate multiple cellular pathways that contribute to replication and host pathology. We have previously shown that latent HIV-1 and HTLV-1 infected cells secrete exosomes that contain short viral RNAs, limited number of genomic RNAs, and viral proteins. These exosomes largely target neighboring cells and activate the NF-кB pathway, leading to cell proliferation and overall better viral replication. In this manuscript, we studied the effects of exosome formation from RVFV infected cells and their function on recipient cells. We initially infected cells, isolated resistant clones, and further purified using dilution cloning. We then characterized these cells as resistant to new RVFV infection, but sensitive to other viral infections, including Venezuelan Equine Encephalitis Virus (VEEV. These clones contained normal markers (i.e. CD63 for exosomes and were able to activate the TLR pathway in recipient reporter cells. Interestingly, the exosome rich preparations, much like their host cell, contained viral RNA (L, M, and S genome. The RNAs were detected using qRT-PCR in both parental and exosomal preparations as well as in CD63 immunoprecipitates. Viral proteins such as N and a modified form of NSs were present in some of these exosomes. Finally, treatment of recipient cells (T- cells and monocytic cells showed

  8. Transient Oral Human Cytomegalovirus Infections Indicate Inefficient Viral Spread from Very Few Initially Infected Cells.

    Science.gov (United States)

    Mayer, Bryan T; Krantz, Elizabeth M; Swan, David; Ferrenberg, James; Simmons, Karen; Selke, Stacy; Huang, Meei-Li; Casper, Corey; Corey, Lawrence; Wald, Anna; Schiffer, Joshua T; Gantt, Soren

    2017-06-15

    Cytomegalovirus (CMV) is acquired by the oral route in children, and primary infection is associated with abundant mucosal replication, as well as the establishment of latency in myeloid cells that results in lifelong infection. The efficiency of primary CMV infection in humans following oral exposure, however, is unknown. We consistently detected self-limited, low-level oral CMV shedding events, which we termed transient CMV infections, in a prospective birth cohort of 30 highly exposed CMV-uninfected infants. We estimated the likelihood of transient oral CMV infections by comparing their observed frequency to that of established primary infections, characterized by persistent high-level shedding, viremia, and seroconversion. We developed mathematical models of viral dynamics upon initial oral CMV infection and validated them using clinical shedding data. Transient infections comprised 76 to 88% of oral CMV shedding events. For this high percentage of transient infections to occur, we identified two mathematical prerequisites: a very small number of initially infected oral cells (1 to 4) and low viral infectivity (<1.5 new cells infected/cell). These observations indicate that oral CMV infection in infants typically begins with a single virus that spreads inefficiently to neighboring cells. Thus, although the incidence of CMV infection is high during infancy, our data provide a mechanistic framework to explain why multiple CMV exposures are typically required before infection is successfully established. These findings imply that a sufficiently primed immune response could prevent CMV from establishing latent infection in humans and support the achievability of a prophylactic CMV vaccine. IMPORTANCE CMV infects the majority of the world's population and is a major cause of birth defects. Developing a vaccine to prevent CMV infection would be extremely valuable but would be facilitated by a better understanding of how natural human CMV infection is acquired. We

  9. Hepatitis B virus DNA integration occurs early in the viral life cycle in an in vitro infection model via NTCP-dependent uptake of enveloped virus particles.

    Science.gov (United States)

    Tu, Thomas; Budzinska, Magdalena A; Vondran, Florian W R; Shackel, Nicholas A; Urban, Stephan

    2018-02-07

    Chronic infection by the Hepatitis B Virus (HBV) is the major contributor to liver disease worldwide. Though HBV replicates via a nuclear episomal DNA (cccDNA), integration of HBV DNA into the host cell genome is regularly observed in the liver of infected patients. While reported as a pro-oncogenic alteration, the mechanism(s) and timing of HBV DNA integration are not well-understood, chiefly due to the lack of in vitro infection models that have detectable integration events. Here, we have established an in vitro system in which integration can be reliably detected following HBV infection. We measured HBV DNA integration using inverse nested PCR in primary human hepatocytes, HepaRG-NTCP, HepG2-NTCP, and Huh7-NTCP cells after HBV infection. Integration was detected in all cell types at a rate of >1 per 10000 cells, with the most consistent detection in Huh7-NTCP cells. Integration rate remained stable between 3 and 9 days post-infection. HBV DNA integration was efficiently blocked by treatment with 200nM of the HBV entry inhibitor Myrcludex B, but not with 10μM Tenofovir, 100U Interferon alpha, or 1μM of the capsid assembly inhibitor GLS4. This suggests integration of HBV DNA occurs immediately after infection of hepatocytes and is likely independent of de novo HBV replication in this model. Site analysis revealed that HBV DNA integrations were distributed over the entire human genome. Further, integrated HBV DNA sequences were consistent with double-stranded linear HBV DNA being the major precursor. Thus, we have established an in vitro system to interrogate the mechanisms of HBV DNA integration. Importance Hepatitis B Virus (HBV) is a common blood-borne pathogen and, following a chronic infection, can cause liver cancer and liver cirrhosis. Integration of HBV DNA into the host genome occurs in all known members of the hepadnaviridae family, despite this form not being necessary for viral replication. HBV DNA integration has been reported to drive liver cancer

  10. Sphingosine kinase-2 maintains viral latency and survival for KSHV-infected endothelial cells.

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    Lu Dai

    Full Text Available Phosphorylation of sphingosine by sphingosine kinases (SphK1 and SphK2 generates sphingosine-1-phosphate (S1P, a bioactive sphingolipid which promotes cancer cell survival and tumor progression in vivo. We have recently reported that targeting SphK2 induces apoptosis for human primary effusion lymphoma (PEL cell lines infected by the Kaposi's sarcoma-associated herpesvirus (KSHV, and this occurs in part through inhibition of canonical NF-κB activation. In contrast, pharmacologic inhibition of SphK2 has minimal impact for uninfected B-cell lines or circulating human B cells from healthy donors. Therefore, we designed additional studies employing primary human endothelial cells to explore mechanisms responsible for the selective death observed for KSHV-infected cells during SphK2 targeting. Using RNA interference and a clinically relevant pharmacologic approach, we have found that targeting SphK2 induces apoptosis selectively for KSHV-infected endothelial cells through induction of viral lytic gene expression. Moreover, this effect occurs through repression of KSHV-microRNAs regulating viral latency and signal transduction, including miR-K12-1 which targets IκBα to facilitate activation of NF-κB, and ectopic expression of miR-K12-1 restores NF-κB activation and viability for KSHV-infected endothelial cells during SphK2 inhibition. These data illuminate a novel survival mechanism and potential therapeutic target for KSHV-infected endothelial cells: SphK2-associated maintenance of viral latency.

  11. Retention on buprenorphine is associated with high levels of maximal viral suppression among HIV-infected opioid dependent released prisoners.

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    Sandra A Springer

    Full Text Available HIV-infected prisoners lose viral suppression within the 12 weeks after release to the community. This prospective study evaluates the use of buprenorphine/naloxone (BPN/NLX as a method to reduce relapse to opioid use and sustain viral suppression among released HIV-infected prisoners meeting criteria for opioid dependence (OD.From 2005-2010, 94 subjects meeting DSM-IV criteria for OD were recruited from a 24-week prospective trial of directly administered antiretroviral therapy (DAART for released HIV-infected prisoners; 50 (53% selected BPN/NLX and were eligible to receive it for 6 months; the remaining 44 (47% selected no BPN/NLX therapy. Maximum viral suppression (MVS, defined as HIV-1 RNA<50 copies/mL, was compared for the BPN/NLX and non-BPN/NLX (N = 44 groups.The two groups were similar, except the BPN/NLX group was significantly more likely to be Hispanic (56.0% v 20.4%, from Hartford (74.4% v 47.7% and have higher mean global health quality of life indicator scores (54.18 v 51.40. MVS after 24 weeks of being released was statistically correlated with 24-week retention on BPN/NLX [AOR = 5.37 (1.15, 25.1], having MVS at the time of prison-release [AOR = 10.5 (3.21, 34.1] and negatively with being Black [AOR = 0.13 (0.03, 0.68]. Receiving DAART or methadone did not correlate with MVS.In recognition that OD is a chronic relapsing disease, strategies that initiate and retain HIV-infected prisoners with OD on BPN/NLX is an important strategy for improving HIV treatment outcomes as a community transition strategy.

  12. Viral Interference and Persistence in Mosquito-Borne Flaviviruses

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    Juan Santiago Salas-Benito

    2015-01-01

    Full Text Available Mosquito-borne flaviviruses are important pathogens for humans, and the detection of two or more flaviviruses cocirculating in the same geographic area has often been reported. However, the epidemiological impact remains to be determined. Mosquito-borne flaviviruses are primarily transmitted through Aedes and Culex mosquitoes; these viruses establish a life-long or persistent infection without apparent pathological effects. This establishment requires a balance between virus replication and the antiviral host response. Viral interference is a phenomenon whereby one virus inhibits the replication of other viruses, and this condition is frequently associated with persistent infections. Viral interference and persistent infection are determined by several factors, such as defective interfering particles, competition for cellular factors required for translation/replication, and the host antiviral response. The interaction between two flaviviruses typically results in viral interference, indicating that these viruses share common features during the replicative cycle in the vector. The potential mechanisms involved in these processes are reviewed here.

  13. P53-mediated rapid induction of apoptosis conveys resistance to viral infection in Drosophila melanogaster.

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    Bo Liu

    2013-02-01

    Full Text Available Arthropod-borne pathogens account for millions of deaths each year. Understanding the genetic mechanisms controlling vector susceptibility to pathogens has profound implications for developing novel strategies for controlling insect-transmitted infectious diseases. The fact that many viruses carry genes that have anti-apoptotic activity has long led to the hypothesis that induction of apoptosis could be a fundamental innate immune response. However, the cellular mechanisms mediating the induction of apoptosis following viral infection remained enigmatic, which has prevented experimental verification of the functional significance of apoptosis in limiting viral infection in insects. In addition, studies with cultured insect cells have shown that there is sometimes a lack of apoptosis, or the pro-apoptotic response happens relatively late, thus casting doubt on the functional significance of apoptosis as an innate immunity. Using in vivo mosquito models and the native route of infection, we found that there is a rapid induction of reaper-like pro-apoptotic genes within a few hours following exposure to DNA or RNA viruses. Recapitulating a similar response in Drosophila, we found that this rapid induction of apoptosis requires the function of P53 and is mediated by a stress-responsive regulatory region upstream of reaper. More importantly, we showed that the rapid induction of apoptosis is responsible for preventing the expression of viral genes and blocking the infection. Genetic changes influencing this rapid induction of reaper-like pro-apoptotic genes led to significant differences in susceptibility to viral infection.

  14. Carbohydrate-Based Ice Recrystallization Inhibitors Increase Infectivity and Thermostability of Viral Vectors

    Science.gov (United States)

    Ghobadloo, Shahrokh M.; Balcerzak, Anna K.; Gargaun, Ana; Muharemagic, Darija; Mironov, Gleb G.; Capicciotti, Chantelle J.; Briard, Jennie G.; Ben, Robert N.; Berezovski, Maxim V.

    2014-07-01

    The inability of vaccines to retain sufficient thermostability has been an obstacle to global vaccination programs. To address this major limitation, we utilized carbohydrate-based ice recrystallization inhibitors (IRIs) to eliminate the cold chain and stabilize the potency of Vaccinia virus (VV), Vesicular Stomatitis virus (VSV) and Herpes virus-1 (HSV-1). The impact of these IRIs was tested on the potency of the viral vectors using a plaque forming unit assay following room temperature storage, cryopreservation with successive freeze-thaw cycles and lyophilization. Viral potency after storage with all three conditions demonstrated that N-octyl-gluconamide (NOGlc) recovered the infectivity of shelf stored VV, 5.6 Log10 PFU mL-1 during 40 days, and HSV-1, 2.7 Log10 PFU mL-1 during 9 days. Carbon-linked antifreeze glycoprotein analogue ornithine-glycine-glycine-galactose (OGG-Gal) increases the recovery of VV and VSV more than 1 Log10 PFU mL-1 after 10 freeze-thaw cycles. In VSV, cryostorage with OGG-Gal maintains high infectivity and reduces temperature-induced aggregation of viral particles by 2 times that of the control. In total, OGG-Gal and NOGlc preserve virus potency during cryostorage. Remarkably, NOGlc has potential to eliminate the cold chain and permit room temperature storage of viral vectors.

  15. Household sanitation is associated with lower risk of bacterial and protozoal enteric infections, but not viral infections and diarrhoea, in a cohort study in a low-income urban neighbourhood in Vellore, India.

    Science.gov (United States)

    Berendes, David; Leon, Juan; Kirby, Amy; Clennon, Julie; Raj, Suraja; Yakubu, Habib; Robb, Katharine; Kartikeyan, Arun; Hemavathy, Priya; Gunasekaran, Annai; Roy, Sheela; Ghale, Ben Chirag; Kumar, J Senthil; Mohan, Venkata Raghava; Kang, Gagandeep; Moe, Christine

    2017-09-01

    This study examined associations between household sanitation and enteric infection - including diarrhoeal-specific outcomes - in children 0-2 years of age in a low-income, dense urban neighbourhood. As part of the MAL-ED study, 230 children in a low-income, urban, Indian neighbourhood provided stool specimens at 14-17 scheduled time points and during diarrhoeal episodes in the first 2 years of life that were analysed for bacterial, parasitic (protozoa and helminths) and viral pathogens. From interviews with caregivers in 100 households, the relationship between the presence (and discharge) of household sanitation facilities and any, pathogen-specific, and diarrhoea-specific enteric infection was tested through mixed-effects Poisson regression models. Few study households (33%) reported having toilets, most of which (82%) discharged into open drains. Controlling for season and household socio-economic status, the presence of a household toilet was associated with lower risks of enteric infection (RR: 0.91, 95% CI: 0.79-1.06), bacterial infection (RR: 0.87, 95% CI: 0.75-1.02) and protozoal infection (RR: 0.64, 95% CI: 0.39-1.04), although not statistically significant, but had no association with diarrhoea (RR: 1.00, 95% CI: 0.68-1.45) or viral infections (RR: 1.12, 95% CI: 0.79-1.60). Models also suggested that the relationship between household toilets discharging to drains and enteric infection risk may vary by season. The presence of a household toilet was associated with lower risk of bacterial and protozoal enteric infections, but not diarrhoea or viral infections, suggesting the health effects of sanitation may be more accurately estimated using outcome measures that account for aetiologic agents. © 2017 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  16. Cost effectiveness of screening strategies for early identification of HIV and HCV infection in injection drug users.

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    Lauren E Cipriano

    Full Text Available To estimate the cost, effectiveness, and cost effectiveness of HIV and HCV screening of injection drug users (IDUs in opioid replacement therapy (ORT.Dynamic compartmental model of HIV and HCV in a population of IDUs and non-IDUs for a representative U.S. urban center with 2.5 million adults (age 15-59.We considered strategies of screening individuals in ORT for HIV, HCV, or both infections by antibody or antibody and viral RNA testing. We evaluated one-time and repeat screening at intervals from annually to once every 3 months. We calculated the number of HIV and HCV infections, quality-adjusted life years (QALYs, costs, and incremental cost-effectiveness ratios (ICERs.Adding HIV and HCV viral RNA testing to antibody testing averts 14.8-30.3 HIV and 3.7-7.7 HCV infections in a screened population of 26,100 IDUs entering ORT over 20 years, depending on screening frequency. Screening for HIV antibodies every 6 months costs $30,700/QALY gained. Screening for HIV antibodies and viral RNA every 6 months has an ICER of $65,900/QALY gained. Strategies including HCV testing have ICERs exceeding $100,000/QALY gained unless awareness of HCV-infection status results in a substantial reduction in needle-sharing behavior.Although annual screening for antibodies to HIV and HCV is modestly cost effective compared to no screening, more frequent screening for HIV provides additional benefit at less cost. Screening individuals in ORT every 3-6 months for HIV infection using both antibody and viral RNA technologies and initiating ART for acute HIV infection appears cost effective.

  17. Global Analysis of a Model of Viral Infection with Latent Stage and Two Types of Target Cells

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    Shuo Liu

    2013-01-01

    Full Text Available By introducing the probability function describing latency of infected cells, we unify some models of viral infection with latent stage. For the case that the probability function is a step function, which implies that the latency period of the infected cells is constant, the corresponding model is a delay differential system. The model with delay of latency and two types of target cells is investigated, and the obtained results show that when the basic reproduction number is less than or equal to unity, the infection-free equilibrium is globally stable, that is, the in-host free virus will be cleared out finally; when the basic reproduction number is greater than unity, the infection equilibrium is globally stable, that is, the viral infection will be chronic and persist in-host. And by comparing the basic reproduction numbers of ordinary differential system and the associated delayed differential system, we think that it is necessary to elect an appropriate type of probability function for predicting the final outcome of viral infection in-host.

  18. Acute mucosal pathogenesis of feline immunodeficiency virus is independent of viral dose in vaginally infected cats

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    Egan Erin A

    2010-01-01

    Full Text Available Abstract Background The mucosal pathogenesis of HIV has been shown to be an important feature of infection and disease progression. HIV-1 infection causes depletion of intestinal lamina propria CD4+ T cells (LPL, therefore, intestinal CD4+ T cell preservation may be a useful correlate of protection in evaluating vaccine candidates. Vaccine studies employing the cat/FIV and macaque/SIV models frequently use high doses of parenterally administered challenge virus to ensure high plasma viremia in control animals. However, it is unclear if loss of mucosal T cells would occur regardless of initial viral inoculum dose. The objective of this study was to determine the acute effect of viral dose on mucosal leukocytes and associated innate and adaptive immune responses. Results Cats were vaginally inoculated with a high, middle or low dose of cell-associated and cell-free FIV. PBMC, serum and plasma were assessed every two weeks with tissues assessed eight weeks following infection. We found that irrespective of mucosally administered viral dose, FIV infection was induced in all cats. However, viremia was present in only half of the cats, and viral dose was unrelated to the development of viremia. Importantly, regardless of viral dose, all cats experienced significant losses of intestinal CD4+ LPL and CD8+ intraepithelial lymphocytes (IEL. Innate immune responses by CD56+CD3- NK cells correlated with aviremia and apparent occult infection but did not protect mucosal T cells. CD4+ and CD8+ T cells in viremic cats were more likely to produce cytokines in response to Gag stimulation, whereas aviremic cats T cells tended to produce cytokines in response to Env stimulation. However, while cell-mediated immune responses in aviremic cats may have helped reduce viral replication, they could not be correlated to the levels of viremia. Robust production of anti-FIV antibodies was positively correlated with the magnitude of viremia. Conclusions Our results indicate

  19. Human Papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women

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    José E. Levi

    Full Text Available HIV-infected women from São Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV and cervical intraepithelial neoplasia (CIN prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD4+ cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%. Twenty (7.5% women were infected by one or more low-risk viruses, 89 (33% by one or more high-risk viruses, and 64 (24% harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD4/µL <100 were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

  20. Human Papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women

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    Levi José E.

    2002-01-01

    Full Text Available HIV-infected women from São Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV and cervical intraepithelial neoplasia (CIN prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD4+ cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%. Twenty (7.5% women were infected by one or more low-risk viruses, 89 (33% by one or more high-risk viruses, and 64 (24% harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD4/µL <100 were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

  1. Depressed Hypoxic and Hypercapnic Ventilatory Responses at Early Stage of Lethal Avian Influenza A Virus Infection in Mice.

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    Jianguo Zhuang

    Full Text Available H5N1 virus infection results in ~60% mortality in patients primarily due to respiratory failure, but the underlying causes of mortality are unclear. The goal of this study is to reveal respiratory disorders occurring at the early stage of infection that may be responsible for subsequent respiratory failure and death. BALB/c mice were intranasally infected with one of two H5N1 virus strains: HK483 (lethal or HK486 (non-lethal virus. Pulmonary ventilation and the responses to hypoxia (HVR; 7% O2 for 3 min and hypercapnia (HCVR; 7% CO2 for 5 min were measured daily at 2 days prior and 1, 2, and 3 days postinfection (dpi and compared to mortality typically by 8 dpi. At 1, 2, and 3 dpi, immunoreactivities (IR of substance P (SP-IR in the nodose ganglion or tyrosine hydroxylase (TH-IR in the carotid body coupled with the nucleoprotein of influenza A (NP-IR was examined in some mice, while arterial blood was collected in others. Our results showed that at 2 and 3 dpi: 1 both viral infections failed to alter body temperature and weight, [Formula: see text], or induce viremia while producing similarly high lung viral titers; 2 HK483, but not HK486, virus induced tachypnea and depressed HVR and HCVR without changes in arterial blood pH and gases; and 3 only HK483 virus led to NP-IR in vagal SP-IR neurons, but not in the carotid body, and increased density of vagal SP-IR neurons. In addition, all HK483, rather than HK486, mice died at 6 to 8 dpi and the earlier death was correlated with more severe depression of HVR and HCVR. Our data suggest that tachypnea and depressed HVR/HCVR occur at the early stage of lethal H5N1 viral infection associated with viral replication and increased SP-IR density in vagal neurons, which may contribute to the respiratory failure and death.

  2. HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell.

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    Mikaël Boullé

    2016-11-01

    Full Text Available Cell-to-cell spread of HIV, a directed mode of viral transmission, has been observed to be more rapid than cell-free infection. However, a mechanism for earlier onset of viral gene expression in cell-to-cell spread was previously uncharacterized. Here we used time-lapse microscopy combined with automated image analysis to quantify the timing of the onset of HIV gene expression in a fluorescent reporter cell line, as well as single cell staining for infection over time in primary cells. We compared cell-to-cell spread of HIV to cell-free infection, and limited both types of transmission to a two-hour window to minimize differences due to virus transit time to the cell. The mean time to detectable onset of viral gene expression in cell-to-cell spread was accelerated by 19% in the reporter cell line and by 35% in peripheral blood mononuclear cells relative to cell-free HIV infection. Neither factors secreted by infected cells, nor contact with infected cells in the absence of transmission, detectably changed onset. We recapitulated the earlier onset by infecting with multiple cell-free viruses per cell. Surprisingly, the acceleration in onset of viral gene expression was not explained by cooperativity between infecting virions. Instead, more rapid onset was consistent with a model where the fastest expressing virus out of the infecting virus pool sets the time for infection independently of the other co-infecting viruses.

  3. Recurrences after oral and genital herpes simplex virus infection. Influence of site of infection and viral type.

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    Lafferty, W E; Coombs, R W; Benedetti, J; Critchlow, C; Corey, L

    1987-06-04

    We prospectively followed 39 adults with concurrent primary herpes simplex virus (HSV) infection (12 with HSV type 1 and 27 with HSV type 2) of the oropharynx and genitalia, caused by the same virus in each person, to evaluate the influence of viral type (HSV-1 vs. HSV-2) and site of infection (oropharyngeal vs. genital) on the frequency of recurrence. The subsequent recurrence patterns of HSV infection differed markedly according to viral type and anatomical site. Oral-labial recurrences developed in 5 of 12 patients with HSV-1 and 1 of 27 patients with HSV-2 (P less than 0.001). Conversely, genital recurrences developed in 24 of 27 patients with HSV-2 and 3 of 12 patients with HSV-1 (P less than 0.01). The mean rate of subsequent genital recurrences (due to HSV-1 and HSV-2) was 0.23 per month, whereas the mean rate of oral-labial recurrences was only 0.04 per month (P less than 0.001). The mean monthly frequencies of recurrence were, in order, genital HSV-2 infections, 0.33 per month; oral-labial HSV-1 infections, 0.12 per month; genital HSV-1 infections, 0.020 per month; and oral HSV-2 infections, 0.001 per month (P less than 0.01 for each comparison). We conclude that the likelihood of reactivation of HSV infection differs between HSV-1 and HSV-2 infections and between the sacral and trigeminal anatomical sites. The sixfold more frequent clinical recurrence rate of genital HSV infections as compared with oral-labial HSV infections may account for the relatively rapid increase in the prevalence of clinically recognized genital herpes in recent years.

  4. Early Detection of Viral Hepatitis Can Save Lives - PSA (:30)

    Centers for Disease Control (CDC) Podcasts

    2010-05-12

    Early detection of viral hepatitis can help prevent liver damage, cirrhosis, and even liver cancer.  Created: 5/12/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 5/12/2010.

  5. HIV sequence diversity during the early phase of infection is associated with HIV DNA reductions during antiretroviral therapy.

    Science.gov (United States)

    Wang, Nidan; Li, Yijia; Han, Yang; Xie, Jing; Li, Taisheng

    2017-06-01

    The association between baseline human immunodeficiency virus (HIV) sequence diversity and HIV DNA decay after the initiation of antiretroviral therapy (ART) remains uncharacterized during the early stages of HIV infection. Samples were obtained from a cohort of 17 patients with early HIV infection (HIV-1 envelope (env) gene was amplified via single genome amplification (SGA) to determine the peripheral plasma HIV quasispecies. We categorized HIV quasispecies into two groups according to baseline viral sequence genetic distance, which was determined by the Poisson-Fitter tool. Total HIV DNA in peripheral blood mononuclear cells (PBMCs), viral load, and T cell subsets were measured prior to and after the initiation of ART. The median SGA sequence number was 17 (range 6-28). At baseline, we identified 7 patients with homogeneous viral populations (designated the Homogeneous group) and 10 patients with heterogeneous viral populations (designated the Heterogeneous group) based on SGA sequences. Both groups exhibited similar HIV DNA decay rates during the first 6 months of ART (P > 0.99), but the Homogenous group experienced more prominent decay than the Heterogeneous group after 6 months (P = 0.037). The Heterogeneous group had higher CD4 cell counts after ART initiation; however, both groups had comparable recovery in terms of CD4/CD8 ratios and CD8 T cell activation levels. Viral population homogeneity upon the initiation of ART is associated with a decrease in HIV DNA levels during ART. J. Med. Virol. 89:982-988, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Mucosal immunization with recombinant adenoviral vectors expressing murine gammaherpesvirus-68 genes M2 and M3 can reduce latent viral load.

    Science.gov (United States)

    Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P; Holst, Peter J

    2009-11-12

    Gammaherpesviruses establish life-long latent infections in their hosts. If the host becomes immunosuppressed, these viruses may reactivate and cause severe disease, and even in immunocompetent individuals the gammaherpesviruses are presumed to have an oncogenic potential. Murine gammaherpesvirus-68 (MHV-68) is a member of the Gammaherpesvirinae subfamily and represents a useful murine model for this category of infections, in which new vaccination strategies may initially be evaluated. Two attenuated variants of MHV-68 have successfully been used as vaccines, but the oncogenic potential of the gammaherpesvirinae speaks against using a similar approach in humans. DNA immunization with plasmids encoding the MHV-68 genes M2 or M3 caused a reduction in either acute or early latent viral load, respectively, but neither immunization had an effect at times later than 14 days post-infection. Adenovirus-based vaccines are substantially more immunogenic than DNA vaccines and can be applied to induce mucosal immunity. Here we show that a significant reduction of the late viral load in the spleens, at 60 days post-infection, was achieved when immunizing mice both intranasally and subcutaneously with adenoviral vectors encoding both M2 and M3. Additionally we show that M3 immunization prevented the usual development of virus-induced splenomegaly at 2-3 weeks post-infection. This is the first time that immunization with a non-replicating vaccine has lead to a significantly reduced viral load at time points beyond 14 days post-infection, and thus demonstrates that a non-replicating vaccine may successfully be employed to reduce the viral burden during chronic gammaherpesvirus infection.

  7. HIV taken by STORM: Super-resolution fluorescence microscopy of a viral infection

    Directory of Open Access Journals (Sweden)

    Pereira Cândida F

    2012-05-01

    Full Text Available Abstract Background The visualization of viral proteins has been hindered by the resolution limit of conventional fluorescent microscopes, as the dimension of any single fluorescent signal is often greater than most virion particles. Super-resolution microscopy has the potential to unveil the distribution of proteins at the resolution approaching electron microscopy without relying on morphological features of existing characteristics of the biological specimen that are needed in EM. Results Using direct stochastic optical reconstruction microscopy (dSTORM to achieve a lateral resolution of 15–20 nm, we quantified the 2-D molecular distribution of the major structural proteins of the infectious human immunodeficiency virus type 1 (HIV-1 before and after infection of lymphoid cells. We determined that the HIV-1 matrix and capsid proteins undergo restructuring soon after HIV-1 infection. Conclusions This study provides the proof-of-concept for the use of dSTORM to visualize the changes in the molecular distribution of viral proteins during an infection.

  8. Estimating Acute Viral Hepatitis Infections From Nationally Reported Cases

    Science.gov (United States)

    Liu, Stephen; Roberts, Henry; Jiles, Ruth B.; Holmberg, Scott D.

    2014-01-01

    Objectives. Because only a fraction of patients with acute viral hepatitis A, B, and C are reported through national surveillance to the Centers for Disease Control and Prevention, we estimated the true numbers. Methods. We applied a simple probabilistic model to estimate the fraction of patients with acute hepatitis A, hepatitis B, and hepatitis C who would have been symptomatic, would have sought health care tests, and would have been reported to health officials in 2011. Results. For hepatitis A, the frequencies of symptoms (85%), care seeking (88%), and reporting (69%) yielded an estimate of 2730 infections (2.0 infections per reported case). For hepatitis B, the frequencies of symptoms (39%), care seeking (88%), and reporting (45%) indicated 18 730 infections (6.5 infections per reported case). For hepatitis C, the frequency of symptoms among injection drug users (13%) and those infected otherwise (48%), proportion seeking care (88%), and percentage reported (53%) indicated 17 100 infections (12.3 infections per reported case). Conclusions. These adjustment factors will allow state and local health authorities to estimate acute hepatitis infections locally and plan prevention activities accordingly. PMID:24432918

  9. Integrase-independent HIV-1 infection is augmented under conditions of DNA damage and produces a viral reservoir

    International Nuclear Information System (INIS)

    Ebina, Hirotaka; Kanemura, Yuka; Suzuki, Yasutsugu; Urata, Kozue; Misawa, Naoko; Koyanagi, Yoshio

    2012-01-01

    HIV-1 possesses a viral protein, integrase (IN), which is necessary for its efficient integration in target cells. However, it has been reported that an IN-defective HIV strain is still capable of integration. Here, we assessed the ability of wild type (WT) HIV-1 to establish infection in the presence of IN inhibitors. We observed a low, yet clear infection of inhibitor-incubated cells infected with WT HIV which was identical to cells infected with IN-deficient HIV, D64A. Furthermore, the IN-independent integration could be enhanced by the pretreatment of cells with DNA-damaging agents suggesting that integration is mediated by a DNA repair system. Moreover, significantly faster viral replication kinetics with augmented viral DNA integration was observed after infection in irradiated cells treated with IN inhibitor compared to nonirradiated cells. Altogether, our results suggest that HIV DNA has integration potential in the presence of an IN inhibitor and may serve as a virus reservoir.

  10. Integrase-independent HIV-1 infection is augmented under conditions of DNA damage and produces a viral reservoir

    Energy Technology Data Exchange (ETDEWEB)

    Ebina, Hirotaka, E-mail: hebina@virus.kyoto-u.ac.jp; Kanemura, Yuka; Suzuki, Yasutsugu; Urata, Kozue; Misawa, Naoko; Koyanagi, Yoshio

    2012-05-25

    HIV-1 possesses a viral protein, integrase (IN), which is necessary for its efficient integration in target cells. However, it has been reported that an IN-defective HIV strain is still capable of integration. Here, we assessed the ability of wild type (WT) HIV-1 to establish infection in the presence of IN inhibitors. We observed a low, yet clear infection of inhibitor-incubated cells infected with WT HIV which was identical to cells infected with IN-deficient HIV, D64A. Furthermore, the IN-independent integration could be enhanced by the pretreatment of cells with DNA-damaging agents suggesting that integration is mediated by a DNA repair system. Moreover, significantly faster viral replication kinetics with augmented viral DNA integration was observed after infection in irradiated cells treated with IN inhibitor compared to nonirradiated cells. Altogether, our results suggest that HIV DNA has integration potential in the presence of an IN inhibitor and may serve as a virus reservoir.

  11. Early-life inflammation, immune response and ageing.

    Science.gov (United States)

    Khan, Imroze; Agashe, Deepa; Rolff, Jens

    2017-03-15

    Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. © 2017 The Author(s).

  12. Neurological manifestations of dengue viral infection

    Directory of Open Access Journals (Sweden)

    Carod-Artal FJ

    2014-10-01

    Full Text Available Francisco Javier Carod-Artal1,21Neurology Department, Raigmore hospital, Inverness, UK; 2Universitat Internacional de Catalunya (UIC, Barcelona, Spain Abstract: Dengue is the most common mosquito-borne viral infection worldwide. There is increased evidence for dengue virus neurotropism, and neurological manifestations could make part of the clinical picture of dengue virus infection in at least 0.5%–7.4% of symptomatic cases. Neurological complications have been classified into dengue virus encephalopathy, dengue virus encephalitis, immune-mediated syndromes (acute disseminated encephalomyelitis, myelitis, Guillain–Barré syndrome, neuritis brachialis, acute cerebellitis, and others, neuromuscular complications (hypokalemic paralysis, transient benign muscle dysfunction and myositis, and dengue-associated stroke. Common neuro-ophthalmic complications are maculopathy and retinal vasculopathy. Pathogenic mechanisms include systemic complications and metabolic disturbances resulting in encephalopathy, direct effect of the virus provoking encephalitis, and postinfectious immune mechanisms causing immune-mediated syndromes. Dengue viruses should be considered as a cause of neurological disorders in endemic regions. Standardized case definitions for specific neurological complications are still needed. Keywords: encephalitis, encephalopathy, dengue fever, neurological complications

  13. Environmental modulation of mucosal immunity : Opportunities in respiratory viral infections

    NARCIS (Netherlands)

    Schijf, M.A.

    2013-01-01

    The exact cause of severe disease in children during primary RSV infections is not completely clear. There is a link with viral load, but differences virus strains do not seem to be the major reason why in some children the disease manifests as a mild cold while others suffer from a severe lower

  14. Hepatitis B and C viral infections among blood donors from rural Ghana.

    Science.gov (United States)

    Nkrumah, B; Owusu, M; Frempong, H O; Averu, P

    2011-09-01

    To investigate the prevalence of Hepatitis B and C infections and co-infections among blood donors in a rural community of Ghana. A retrospective study. Samples of blood donated between January 2007 and December 2008 were screen for Hepatitis B and C viruses at the Agogo Presbyterian Hospital. The prevalence of Hepatitis B viral (HBV) infection was highest in females 21.4% (95% CI: 11.6-34.4) in 2006 than males in the same year 13.2% (95% CI: 10.8-15.9). Hepatitis C viral (HCV) infection was highest among males at 11.6% (95% CI: 9.5-13.8) in 2007. HBV and HCV co-infection was higher in males 2.6% (95% CI: 1.6-3.8) than females 1.3% (95% CI: 0-7.0) in 2007. The overall prevalence of HBV and HCV was 13.8% (95% CI: 11.4-16.4) and 9.4% (95% CI: 7.4-11.6) respectively in 2006. The rate of co-infection of HBV and HCV however increased from 1.6% (95% CI: 0.8-2.7) in 2006 to 2.2% (95% CI: 1.3-3.2) in 2008 in males and from 0% (95% CI: 0-6.4) in 2006 to 1.2% (95% CI: 0-6.5) in 2008 in females. The single infections of HBV and HCV reduced but co-infection of these transfusion transmitted infections (TTI) increased. Measures such as more sensitive techniques and education must be employed in these areas.

  15. A comparative review of HLA associations with hepatitis B and C viral infections across global populations

    Institute of Scientific and Technical Information of China (English)

    Rashmi Singh; Rashmi Kaul; Anil Kaul; Khalid Khan

    2007-01-01

    Hepatitis B (HBV) and hepatitis C (HCV) viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma (HCC). Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen (HLA) associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1*11/*12 alleles and DQB1*0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1*03 and *07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors (KIR) of natural killer (NK) cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance ofchronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific

  16. Flavonoids: promising natural compounds against viral infections.

    Science.gov (United States)

    Zakaryan, Hovakim; Arabyan, Erik; Oo, Adrian; Zandi, Keivan

    2017-09-01

    Flavonoids are widely distributed as secondary metabolites produced by plants and play important roles in plant physiology, having a variety of potential biological benefits such as antioxidant, anti-inflammatory, anticancer, antibacterial, antifungal and antiviral activity. Different flavonoids have been investigated for their potential antiviral activities and several of them exhibited significant antiviral properties in in vitro and even in vivo studies. This review summarizes the evidence for antiviral activity of different flavonoids, highlighting, where investigated, the cellular and molecular mechanisms of action on viruses. We also present future perspectives on therapeutic applications of flavonoids against viral infections.

  17. Evaluation of serial urine viral cultures for the diagnosis of cytomegalovirus infection in neonates and infants.

    Science.gov (United States)

    Chisholm, Karen M; Aziz, Natali; McDowell, Michal; Guo, Frances P; Srinivas, Nivedita; Benitz, William E; Norton, Mary E; Gutierrez, Kathleen; Folkins, Ann K; Pinsky, Benjamin A

    2014-01-01

    Cytomegalovirus (CMV) is the most common cause of congenital infection worldwide. Urine viral culture is the standard for CMV diagnosis in neonates and infants. The objectives of this study were to compare the performance of serial paired rapid shell vial cultures (SVC) and routine viral cultures (RVC), and to determine the optimal number of cultures needed to detect positive cases. From 2001 to 2011, all paired CMV SVC and RVC performed on neonates and infants less than 100 days of age were recorded. Testing episodes were defined as sets of cultures performed within 7 days of one another. A total of 1264 neonates and infants underwent 1478 testing episodes; 68 (5.4%) had at least one episode with a positive CMV culture. In episodes where CMV was detected before day 21 of life, the first specimen was positive in 100% (16/16) of cases. When testing occurred after 21 days of life, the first specimen was positive in 82.7% (43/52) of cases, requiring three cultures to reach 100% detection. The SVC was more prone to assay failure than RVC. Overall, when RVC was compared to SVC, there was 86.0% positive agreement and 99.9% negative agreement. In conclusion, three serial urine samples are necessary for detection of CMV in specimens collected between day of life 22 and 99, while one sample may be sufficient on or before day of life 21. Though SVC was more sensitive than RVC, the risk of SVC failure supports the use of multimodality testing to optimize detection.

  18. 3,4-Methylenedioxymethamphetamine (MDMA) alters acute gammaherpesvirus burden and limits Interleukin 27 responses in a mouse model of viral infection

    Science.gov (United States)

    Nelson, Daniel A.; Singh, Sam J.; Young, Amy B.; Tolbert, Melanie D.; Bost, Kenneth L.

    2011-01-01

    Aims To test whether 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) abuse might increase the susceptibility, or alter the immune response, to murine gammaherpesvirus 68 (HV-68) and/or bacterial lipopolysaccharide. Methods Groups of experimental and control mice were subjected to three day binges of MDMA, and the effect of this drug abuse on acute and latent HV-68 viral burden were assessed. In vitro and in vivo studies were also performed to assess the MDMA effect on IL-27 expression in virally infected or LPS-exposed macrophages and dendritic cells, and latently infected animals, exposed to this drug of abuse. Results Acute viral burden was significantly increased in MDMA-treated mice when compared to controls. However the latent viral burden, and physiological and behavioral responses were not altered in infected mice despite repeated bingeing with MDMA. MDMA could limit the IL-27 response of HV-68 infected or LPS-exposed macrophages and dendritic cells in vitro and in vivo, demonstrating the ability of this drug to alter normal cytokine responses in the context of a viral infection and/or a TLR4 agonist. Conclusion MDMA bingeing could alter the host’s immune response resulting in greater acute viral replication and reductions in the production of the cytokine, IL-27 during immune responses. PMID:21269783

  19. Studies on some biochemical parameters in viral hepatitis patients

    International Nuclear Information System (INIS)

    El-Sherbiny, E.M.

    2002-01-01

    The present investigation deals with studying liver amino transferases (ALT. AST). Cholesterol and triglycerides. As well as testosterone and protection hormones in blood of Egyptian men infected with hepatitis C virus.hepatitis B virus and mixed B and C viruses. These biochemical parameters were evaluated to be used in diagnosis and prognosis of viral hepatitis. Which considered the most important health problem in Egypt and developing countries. Biochemical analysis were performed using spectrophotometric and radioimmunoassay techniques. All data will be subjected to statistical analysis in order to detect the most suitable biochemical analysis that can be used as specific tests for early diagnosis of viral hepatitis and to detect the parameters that show abnormalities among the different groups of infected patients. The data revealed that AST and ALT levels were increased in all patient groups. Concerning the level of triglycerides, it was increased only in the group of mixed viral hepatitis B and C, while cholesterol showed non-significant changes in all viral hepatitis groups. The sex hormone testosterone was decreased in all infected patients while the prolactin level was increased only in case of patients infected with mixed B and C viruses. However, these abnormal values in such sex hormones play a serious role in male sterility

  20. Disruption of Claudin-1 Expression by miRNA-182 Alters the Susceptibility to Viral Infectivity in HCV Cell Models

    Directory of Open Access Journals (Sweden)

    Sarah E. Riad

    2018-03-01

    Full Text Available HCV entry involves a complex interplay between viral and host molecules. During post-binding interactions, the viral E2 complexes with CD81 receptor for delivery to the tight junction proteins CLDN1 and OCLN, which aid in viral internalization. Targeting HCV entry receptors represents an appealing approach to inhibit viral infectivity. This study aimed at investigating the impact of targeting CLDN1 by microRNAs on HCV infectivity. miR-155 was previously shown to target the 3′UTR of CLDN1 mRNA. Therefore, miR-155 was used as a control in this study. In-silico analysis and luciferase reporter assay were utilized to identify potential targeting miRNAs. The impact of the identified miRNAs on CLDN1 mRNA and protein expression was examined by qRT-PCR, indirect immunofluorescence and western blotting, respectively. The role of the selected miRNAs on HCV infectivity was assessed by measuring the viral load following the ectopic expression of the selected miRNAs. miR-182 was identified in-silico and by experimental validation to target CLDN1. Both miR-155 and miR-182 inhibited CLDN1 mRNA and protein expression in infected Huh7 cells. Ectopic expression of miR-155 increased, while miR-182 reduced the viral load. In conclusion, despite repressing CLDN1, the impact of miR-155 and miR-182 on HCV infectivity is contradictory. Ectopic miR-182 expression is suggested as an upstream regulator of the entry factor CLDN1, harnessing HCV infection.

  1. Viral infections in acute graft-versus-host disease: a review of diagnostic and therapeutic approaches.

    Science.gov (United States)

    Tong, Lana X; Worswick, Scott D

    2015-04-01

    While immunosuppressive therapy for acute graft-versus-host disease (aGVHD) advances, viral reactivation has been found to be an increasingly common complication in these patients. Dermatologists may often be consulted on inpatient services for evaluation. We investigated the literature for the role of viral infections in aGVHD and review the current evidence regarding management. Articles in the public domain regarding aGVHD, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, hepatitis viruses, parvovirus B19, and respiratory viruses were included. Dermatologic findings vary between different viral antigens, and some infections may be a marker for the development of aGVHD or worsen prognosis. The heterogeneous cohorts of the studies reviewed often preclude direct comparison between results. The relationship between viral reactivation and aGVHD may be bidirectional and is worthy of further exploration. Additional studies are needed to determine appropriate prophylaxis and treatment. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  2. Saffold virus, a human Theiler's-like cardiovirus, is ubiquitous and causes infection early in life.

    Directory of Open Access Journals (Sweden)

    Jan Zoll

    2009-05-01

    Full Text Available The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus. In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV and Theiler's murine encephalomyelits virus (TMEV. The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV. The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3 isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible

  3. Viral infection, proliferation, and hyperplasia of Hofbauer cells and absence of inflammation characterize the placental pathology of fetuses with congenital Zika virus infection.

    Science.gov (United States)

    Schwartz, David A

    2017-06-01

    Attention is increasingly focused on the potential mechanism(s) for Zika virus infection to be transmitted from an infected mother to her fetus. This communication addresses current evidence for the role of the placenta in vertical transmission of the Zika virus. Placentas from second and third trimester fetuses with confirmed intrauterine Zika virus infection were examined with routine staining to determine the spectrum of pathologic changes. In addition, immunohistochemical staining for macrophages and nuclear proliferation antigens was performed. Viral localization was identified using RNA hybridization. These observations were combined with the recent published results of placental pathology to increase the strength of the pathology data. Results were correlated with published data from experimental studies of Zika virus infection in placental cells and chorionic villous explants. Placentas from fetuses with congenital Zika virus infection are concordant in not having viral-induced placental inflammation. Special stains reveal proliferation and prominent hyperplasia of placental stromal macrophages, termed Hofbauer cells, in the chorionic villi of infected placentas. Zika virus infection is present in Hofbauer cells from second and third trimester placentas. Experimental studies and placentae from infected fetuses reveal that the spectrum of placental cell types infected with the Zika virus is broader during the first trimester than later in gestation. Inflammatory abnormalities of the placenta are not a component of vertical transmission of the Zika virus. The major placental response in second and third trimester transplacental Zika virus infection is proliferation and hyperplasia of Hofbauer cells, which also demonstrate viral infection.

  4. Pediatric Viral Exanthema: A Review Article

    Directory of Open Access Journals (Sweden)

    Mohammed Jafar Saffar

    2017-04-01

    Full Text Available Context Many diseases caused by viral agents are associated with fever and cutaneous manifestations. Viral exanthema is a widespread nonspecific skin rash, commonly characterized by generalized eruption of erythematous macules and papular lesions. Although these rashes are mostly benign and self-limited, some may be serious and life-threatening. Differentiation between severe and benign types is clinically important and life-saving. Evidence Acquisition In this narrative review, electronic databases, including Google Scholar, Science Direct, PubMed (including Medline, Web of Science, Scientific Information Database, and Scopus, were searched. We conducted a narrative review of papers published on pediatric viral exanthema during 2000 - 2016. The used keywords included “viral exanthema”, “fever”, and “skin rash”. Articles on skin rash, caused by drug reactions or nonviral exanthema, were excluded. Results Different viral agents can cause different types of skin reactions. Cutaneous manifestations and skin rashes can be categorized, based on the form of the rash (macular, papular, vesicular, blistery, petechial, and purpuric or the general term, which denotes illnesses such as measles-like morbilliform rash, rubella or rubelliform rash, and scarlatiniform rash, a scarlet-fever like infection. Conclusions Based on the findings, a systematic approach relying on accurate history-taking and analysis of epidemiological cues and rash characteristics is of great significance.

  5. The intermediate filament network protein, vimentin, is required for parvoviral infection

    Energy Technology Data Exchange (ETDEWEB)

    Fay, Nikta; Panté, Nelly, E-mail: pante@zoology.ubc.ca

    2013-09-15

    Intermediate filaments (IFs) have recently been shown to serve novel roles during infection by many viruses. Here we have begun to study the role of IFs during the early steps of infection by the parvovirus minute virus of mice (MVM). We found that during early infection with MVM, after endosomal escape, the vimentin IF network was considerably altered, yielding collapsed immunofluorescence staining near the nuclear periphery. Furthermore, we found that vimentin plays an important role in the life cycle of MVM. The number of cells, which successfully replicated MVM, was reduced in infected cells in which the vimentin network was genetically or pharmacologically modified; viral endocytosis, however, remained unaltered. Perinuclear accumulation of MVM-containing vesicles was reduced in cells lacking vimentin. Our data suggests that vimentin is required for the MVM life cycle, presenting possibly a dual role: (1) following MVM escape from endosomes and (2) during endosomal trafficking of MVM. - Highlights: • MVM infection changes the distribution of the vimentin network to perinuclear regions. • Disrupting the vimentin network with acrylamide decreases MVM replication. • MVM replication is significantly reduced in vimentin-null cells. • Distribution of MVM-containing vesicles is affected in MVM infected vimentin-null cells.

  6. The intermediate filament network protein, vimentin, is required for parvoviral infection

    International Nuclear Information System (INIS)

    Fay, Nikta; Panté, Nelly

    2013-01-01

    Intermediate filaments (IFs) have recently been shown to serve novel roles during infection by many viruses. Here we have begun to study the role of IFs during the early steps of infection by the parvovirus minute virus of mice (MVM). We found that during early infection with MVM, after endosomal escape, the vimentin IF network was considerably altered, yielding collapsed immunofluorescence staining near the nuclear periphery. Furthermore, we found that vimentin plays an important role in the life cycle of MVM. The number of cells, which successfully replicated MVM, was reduced in infected cells in which the vimentin network was genetically or pharmacologically modified; viral endocytosis, however, remained unaltered. Perinuclear accumulation of MVM-containing vesicles was reduced in cells lacking vimentin. Our data suggests that vimentin is required for the MVM life cycle, presenting possibly a dual role: (1) following MVM escape from endosomes and (2) during endosomal trafficking of MVM. - Highlights: • MVM infection changes the distribution of the vimentin network to perinuclear regions. • Disrupting the vimentin network with acrylamide decreases MVM replication. • MVM replication is significantly reduced in vimentin-null cells. • Distribution of MVM-containing vesicles is affected in MVM infected vimentin-null cells

  7. Real-time PCR versus viral culture on urine as a gold standard in the diagnosis of congenital cytomegalovirus infection

    NARCIS (Netherlands)

    de Vries, Jutte J. C.; van der Eijk, Annemiek A.; Wolthers, Katja C.; Rusman, Lisette G.; Pas, Suzan D.; Molenkamp, Richard; Claas, Eric C.; Kroes, Aloys C. M.; Vossen, Ann C. T. M.

    2012-01-01

    Background: Cytomegalovirus (CMV) infection is the most common cause of congenital infection. Whereas CMV PCR has replaced viral culture and antigen detection in immunocompromised patients because of higher sensitivity, viral culture of neonatal urine is still referred to as the gold standard in the

  8. Viral entry pathways: the example of common cold viruses.

    Science.gov (United States)

    Blaas, Dieter

    2016-05-01

    For infection, viruses deliver their genomes into the host cell. These nucleic acids are usually tightly packed within the viral capsid, which, in turn, is often further enveloped within a lipid membrane. Both protect them against the hostile environment. Proteins and/or lipids on the viral particle promote attachment to the cell surface and internalization. They are likewise often involved in release of the genome inside the cell for its use as a blueprint for production of new viruses. In the following, I shall cursorily discuss the early more general steps of viral infection that include receptor recognition, uptake into the cell, and uncoating of the viral genome. The later sections will concentrate on human rhinoviruses, the main cause of the common cold, with respect to the above processes. Much of what is known on the underlying mechanisms has been worked out by Renate Fuchs at the Medical University of Vienna.

  9. Development of a chick bioassay for determination of infectivity of viral pathogens in poultry litter.

    Science.gov (United States)

    Islam, A F M F; Walkden-Brown, S W; Groves, P J; Wells, B

    2013-01-01

    To develop a chicken bioassay to detect infective viral pathogens in poultry litter and to determine the effects of type of chicken and age of exposure, as well as the effect of simulated litter transportation, on the level of viral infectivity detected. A 5 × 2 × 2 factorial design, plus negative controls. Five chicken litters, including two with deliberate contamination (one transported and one not), two chicken types (specific-pathogen-free (SPF) Leghorns and Cobb broilers) and two ages at initial exposure (days 1 and 8). Two replicates of each treatment combination. The 10 chickens in each of 22 isolators were either exposed (20 isolators) or not (2 isolators) to 8 L of previously used or deliberately contaminated poultry litter in two deep scratch trays. At day 35 post-exposure, sera were assayed for antibodies against chicken anaemia virus (CAV), infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV), Newcastle disease virus (NDV) and fowl adenovirus (FAV). Spleen samples were tested for Marek's disease virus (MDV) using real-time polymerase chain reaction. The bioassay detected CAV, IBDV and FAV, but not NDV, IBV or MDV, in chickens exposed to infected litters. Infection in SPF chickens was detected with greater sensitivity than in the broiler chickens. Sensitivity increased with age at exposure in broiler but not SPF chickens. Simulated transportation for 24 h had little effect on pathogen detection. A bioassay based on the exposure of day-old SPF chickens to poultry litter and measurement of seroconversion at day 35 post-exposure is a useful semi-quantitative assay for viral infectivity in poultry litter, with overnight transportation of litter having little effect on the level of viral infectivity detected. This bioassay has applications in research on litter treatment protocols. © 2013 The Authors. Australian Veterinary Journal © 2013 Australian Veterinary Association.

  10. Viral Infectivity Markers in Donor Blood: A Retrospective Study of ...

    African Journals Online (AJOL)

    A total of 12,540 homologous donors seen between 1993 and 1999 at the University of Maiduguri Teaching Hospital (U.M.T.H) blood bank were analysed with respect to the frequency of viral infectivity markers (HBsAg and HIV antibodies) as it relates to donor categories. Fifteen percent and 4.07% of voluntary donors were ...

  11. Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

    Science.gov (United States)

    Chu, Li-Wei; Huang, Yi-Lung; Lee, Jin-Hui; Huang, Long-Ying; Chen, Wei-Jun; Lin, Ya-Hsuan; Chen, Jyun-Yu; Xiang, Rui; Lee, Chau-Hwang; Ping, Yueh-Hsin

    2014-01-01

    Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.

  12. Nuclear sensing of viral DNA, epigenetic regulation of herpes simplex virus infection, and innate immunity

    International Nuclear Information System (INIS)

    Knipe, David M.

    2015-01-01

    Herpes simplex virus (HSV) undergoes a lytic infection in epithelial cells and a latent infection in neuronal cells, and epigenetic mechanisms play a major role in the differential gene expression under the two conditions. HSV viron DNA is not associated with histones but is rapidly loaded with heterochromatin upon entry into the cell. Viral proteins promote reversal of the epigenetic silencing in epithelial cells while the viral latency-associated transcript promotes additional heterochromatin in neuronal cells. The cellular sensors that initiate the chromatinization of foreign DNA have not been fully defined. IFI16 and cGAS are both essential for innate sensing of HSV DNA, and new evidence shows how they work together to initiate innate signaling. IFI16 also plays a role in the heterochromatinization of HSV DNA, and this review will examine how IFI16 integrates epigenetic regulation and innate sensing of foreign viral DNA to show how these two responses are related. - Highlights: • HSV lytic and latent gene expression is regulated differentially by epigenetic processes. • The sensors of foreign DNA have not been defined fully. • IFI16 and cGAS cooperate to sense viral DNA in HSV-infected cells. • IFI16 plays a role in both innate sensing of HSV DNA and in restricting its expression

  13. Nuclear sensing of viral DNA, epigenetic regulation of herpes simplex virus infection, and innate immunity

    Energy Technology Data Exchange (ETDEWEB)

    Knipe, David M., E-mail: david_knipe@hms.harvard.edu

    2015-05-15

    Herpes simplex virus (HSV) undergoes a lytic infection in epithelial cells and a latent infection in neuronal cells, and epigenetic mechanisms play a major role in the differential gene expression under the two conditions. HSV viron DNA is not associated with histones but is rapidly loaded with heterochromatin upon entry into the cell. Viral proteins promote reversal of the epigenetic silencing in epithelial cells while the viral latency-associated transcript promotes additional heterochromatin in neuronal cells. The cellular sensors that initiate the chromatinization of foreign DNA have not been fully defined. IFI16 and cGAS are both essential for innate sensing of HSV DNA, and new evidence shows how they work together to initiate innate signaling. IFI16 also plays a role in the heterochromatinization of HSV DNA, and this review will examine how IFI16 integrates epigenetic regulation and innate sensing of foreign viral DNA to show how these two responses are related. - Highlights: • HSV lytic and latent gene expression is regulated differentially by epigenetic processes. • The sensors of foreign DNA have not been defined fully. • IFI16 and cGAS cooperate to sense viral DNA in HSV-infected cells. • IFI16 plays a role in both innate sensing of HSV DNA and in restricting its expression.

  14. Deteccion de citomegalovirus mediante la tecnica de inmunoperoxidasa y aislamiento viral Cytomegalovirus detection by Immunoperoxidase assay and viral isolation

    Directory of Open Access Journals (Sweden)

    Maritza Alvarez

    1991-06-01

    Full Text Available En el presente estudio se comparó la técnica de inmunoperoxidasa para la detección de citomegalovirus (IPCMV utilizando anticuerpos monoclonales que reconocen proteínas precoces virales con el método convencional de aislamiento viral en fibroblastos humanos. Un total de 150 muestras de orina fueron examinadas encontrando una sensibilidad de un 89.8% y una especificidad de 91.3% de la técnica de IPCMV comparada con el aislamiento viral. Una de las ventajas que presentó la IPCMV fue la rapidez con que fueron obtenidos los resultados (48 horas mientras que el aislamiento viral fue como promedio 14 días.An Immunoperoxidase assay was applied to detect early antigens of Cytomegalovirus (CMV in 150 urine samples from immunocompromised patients, using the commercial available monoclonal antibody against CMV El3. The detection of early antigen by IP (IPCMV is compared to the conventional cell culture isolation regarding specificity and sensitivity in order to evaluate is usefulness in the diagnostic of CMV infections. The IPCMV showed a sensitivity of 89.8% and a specificity of 91.3% when compared to the isolation method. The great advantage of the IPCMV is based on the shorter time results are achieved, since 48-72 Hs can be enough to provide evidence of CMV infection, while in the isolation technique cytopatho-genic effect was present around 14 days after sample inoculation.

  15. Association between depressive symptoms, CD4 count and HIV viral suppression among HIV-HCV co-infected people.

    Science.gov (United States)

    Aibibula, Wusiman; Cox, Joseph; Hamelin, Anne-Marie; Moodie, Erica E M; Anema, Aranka; Klein, Marina B; Brassard, Paul

    2018-05-01

    Depressive symptoms are associated with poor HIV viral control and immune recovery among people living with HIV. However, no prior studies assessed this association exclusively among people co-infected with HIV-hepatitis C virus (HCV). While people with HIV only and those with HIV-HCV co-infection share many characteristics, co-infected people may become more susceptible to the effects of depressive symptoms on health outcomes. We assessed this association exclusively among people co-infected with HIV-HCV in Canada using data from the Food Security & HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC). Stabilized inverse probability weighted marginal structural model was used to account for potential time-varying confounders. A total of 725 participants were enrolled between 2012 and 2015. At baseline, 52% of participants reported depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count was 466 (IQR 300-665). People experiencing depressive symptoms had 1.32 times (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had comparable CD4 count to people who did not experience depressive symptoms (fold change of CD4 = 0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a risk factor for incomplete short-term HIV viral suppression among people co-infected with HIV-HCV. Therefore, depressive symptoms screening and related counseling may improve HIV related health outcomes and reduce HIV transmission.

  16. Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

    Science.gov (United States)

    Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

    2014-01-01

    The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initial control of MCMV, although at later time points, CD70-/- mice became more susceptible to MCMV infection. The heightened cytokine response during the early phase of MCMV infection in CD70-/- mice was paralleled by a reduction in regulatory T cells (Treg). Treg from naïve CD70-/- mice were not as efficient at suppressing T cell proliferation compared to Treg from naïve WT mice and depletion of Treg during MCMV infection in Foxp3-DTR mice or in WT mice recapitulated the phenotype observed in CD70-/- mice. Our study demonstrates that while CD70 is required for the activation of the antiviral adaptive response, it has a regulatory role in early cytokine responses to viruses such as MCMV, possibly through maintenance of Treg survival and function. PMID:24913981

  17. Viral and immunological factors associated with breast milk transmission of SIV in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Fresh Lynn

    2004-07-01

    Full Text Available Abstract Background The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. To evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of Simian Immunodeficiency Virus (SIV in lactating rhesus macaques (Macaca mulatta as a model of natural breast milk transmission of HIV. Results Fourteen lactating macaques were infected intravenously with SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their suckling infants throughout the disease course. Transmission was observed in 10 mother-infant pairs over a one-year period. Two mothers transmitted virus during the period of initial viremia 14–21 days post inoculation (p.i. and were classified as early transmitters. Peak viral loads in milk and plasma of early transmitters were similar to other animals, however the early transmitters subsequently displayed a rapid progressor phenotype and failed to control virus expression as well as other animals at 56 days p.i. Eight mothers were classified as late transmitters, with infant infection detected at time points in the chronic stage of the maternal SIV disease course (81 to 360 days. Plasma viral loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late transmitters and non-transmitters. Late breast milk transmission, however, was correlated with higher average milk viral loads and more persistent viral expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four mothers failed to transmit virus, despite disease progression and continuous lactation. Conclusion These studies validate the SIV-infected rhesus macaque as a model for breast milk transmission of HIV. As observed in studies of HIV-infected women, transmission occurred at time points throughout the period of lactation. Transmission during the

  18. Regulation of T cell migration during viral infection: role of adhesion molecules and chemokines

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Nansen, Anneline; Madsen, Andreas Nygaard

    2003-01-01

    T cell mediated immunity and in particular CD8+ T cells are pivotal for the control of most viral infections. T cells exclusively exert their antiviral effect through close cellular interaction with relevant virus-infected target cells in vivo. It is therefore imperative that efficient mechanisms...

  19. Impact of early life exposures to geohelminth infections on the development of vaccine immunity, allergic sensitization, and allergic inflammatory diseases in children living in tropical Ecuador: the ECUAVIDA birth cohort study

    Directory of Open Access Journals (Sweden)

    Sandoval Carlos A

    2011-06-01

    Full Text Available Abstract Background Geohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children. There is growing concern that geohelminth infections, particularly exposures occurring during early life in utero through maternal infections or during infancy, may affect vaccine immunogenicity in populations among whom these infections are endemic. Further, the low prevalence of allergic disease in the rural Tropics has been attributed to the immune modulatory effects of these infections and there is concern that widespread use of anthelmintic treatment in high-risk groups may be associated with an increase in the prevalence of allergic diseases. Because the most widely used vaccines are administered during the first year of life and the antecedents of allergic disease are considered to occur in early childhood, the present study has been designed to investigate the impact of early exposures to geohelminths on the development of protective immunity to vaccines, allergic sensitization, and allergic disease. Methods/Design A cohort of 2,403 neonates followed up to 8 years of age. Primary exposures are infections with geohelminth parasites during the last trimester of pregnancy and the first 2 years of life. Primary study outcomes are the development of protective immunity to common childhood vaccines (i.e. rotavirus, Haemophilus influenzae type B, Hepatitis B, tetanus toxoid, and oral poliovirus type 3 during the first 5 years of life, the development of eczema by 3 years of age, the development of allergen skin test reactivity at 5 years of age, and the development of asthma at 5 and 8 years of age. Potential immunological mechanisms by which geohelminth infections may affect the study outcomes will be investigated also. Discussion The study will provide information on the potential effects of early exposures to

  20. Soluble rhesus lymphocryptovirus gp350 protects against infection and reduces viral loads in animals that become infected with virus after challenge.

    Directory of Open Access Journals (Sweden)

    Junji Sashihara

    2011-10-01

    Full Text Available Epstein-Barr virus (EBV is a human lymphocryptovirus that is associated with several malignancies. Elevated EBV DNA in the blood is observed in transplant recipients prior to, and at the time of post-transplant lymphoproliferative disease; thus, a vaccine that either prevents EBV infection or lowers the viral load might reduce certain EBV malignancies. Two major approaches have been suggested for an EBV vaccine- immunization with either EBV glycoprotein 350 (gp350 or EBV latency proteins (e.g. EBV nuclear antigens [EBNAs]. No comparative trials, however, have been performed. Rhesus lymphocryptovirus (LCV encodes a homolog for each gene in EBV and infection of monkeys reproduces the clinical, immunologic, and virologic features of both acute and latent EBV infection. We vaccinated rhesus monkeys at 0, 4 and 12 weeks with (a soluble rhesus LCV gp350, (b virus-like replicon particles (VRPs expressing rhesus LCV gp350, (c VRPs expressing rhesus LCV gp350, EBNA-3A, and EBNA-3B, or (d PBS. Animals vaccinated with soluble gp350 produced higher levels of antibody to the glycoprotein than those vaccinated with VRPs expressing gp350. Animals vaccinated with VRPs expressing EBNA-3A and EBNA-3B developed LCV-specific CD4 and CD8 T cell immunity to these proteins, while VRPs expressing gp350 did not induce detectable T cell immunity to gp350. After challenge with rhesus LCV, animals vaccinated with soluble rhesus LCV gp350 had the best level of protection against infection based on seroconversion, viral DNA, and viral RNA in the blood after challenge. Surprisingly, animals vaccinated with gp350 that became infected had the lowest LCV DNA loads in the blood at 23 months after challenge. These studies indicate that gp350 is critical for both protection against infection with rhesus LCV and for reducing the viral load in animals that become infected after challenge. Our results suggest that additional trials with soluble EBV gp350 alone, or in combination with

  1. Viral infections stimulate the metabolism and shape prokaryotic assemblages in submarine mud volcanoes.

    Science.gov (United States)

    Corinaldesi, Cinzia; Dell'Anno, Antonio; Danovaro, Roberto

    2012-06-01

    Mud volcanoes are geological structures in the oceans that have key roles in the functioning of the global ecosystem. Information on the dynamics of benthic viruses and their interactions with prokaryotes in mud volcano ecosystems is still completely lacking. We investigated the impact of viral infection on the mortality and assemblage structure of benthic prokaryotes of five mud volcanoes in the Mediterranean Sea. Mud volcano sediments promote high rates of viral production (1.65-7.89 × 10(9) viruses g(-1) d(-1)), viral-induced prokaryotic mortality (VIPM) (33% cells killed per day) and heterotrophic prokaryotic production (3.0-8.3 μgC g(-1) d(-1)) when compared with sediments outside the mud volcano area. The viral shunt (that is, the microbial biomass converted into dissolved organic matter as a result of viral infection, and thus diverted away from higher trophic levels) provides 49 mgC m(-2) d(-1), thus fuelling the metabolism of uninfected prokaryotes and contributing to the total C budget. Bacteria are the dominant components of prokaryotic assemblages in surface sediments of mud volcanoes, whereas archaea dominate the subsurface sediment layers. Multivariate multiple regression analyses show that prokaryotic assemblage composition is not only dependant on the geochemical features and processes of mud volcano ecosystems but also on synergistic interactions between bottom-up (that is, trophic resources) and top-down (that is, VIPM) controlling factors. Overall, these findings highlight the significant role of the viral shunt in sustaining the metabolism of prokaryotes and shaping their assemblage structure in mud volcano sediments, and they provide new clues for our understanding of the functioning of cold-seep ecosystems.

  2. Early-life Socio-economic Status and Adult Health: The Role of Positive Affect.

    Science.gov (United States)

    Murdock, Kyle W; LeRoy, Angie S; Fagundes, Christopher P

    2017-08-01

    The aim of this paper is to develop a further understanding of the relationship between early-life socio-economic status (SES) and adult health disparities. This was accomplished through evaluation of state indicators of positive and negative affect as mechanisms through which early-life SES was associated with susceptibility to a rhinovirus (i.e. the common cold). Analyses were conducted among 286 adults in a viral challenge study in which participants were exposed to a rhinovirus via nasal drops and cold symptoms were evaluated over a period of 5 days. Participant age, body mass index, sex, education, ethnicity, pre-challenge virus-specific antibody titres and subjective adult SES, along with virus type and season of participation, were included as covariates. Early-life SES was associated with cold incidence through state positive affect, but not state negative affect. In addition, contrast analysis indicated that the indirect effect through state positive affect was stronger than the indirect effect through state negative affect. Findings provide further support for early-life SES being an important variable associated with adult health, and that state self-reported positive affect may be an underlying mechanism associated with susceptibility to rhinoviruses. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Viral tropism and pathology associated with viral hemorrhagic septicemia in larval and juvenile Pacific herring

    Science.gov (United States)

    Lovy, Jan; Lewis, N.L.; Hershberger, P.K.; Bennett, W.; Meyers, T.R.; Garver, K.A.

    2012-01-01

    Viral hemorrhagic septicemia virus (VHSV) genotype IVa causes mass mortality in wild Pacific herring, a species of economic value, in the Northeast Pacific Ocean. Young of the year herring are particularly susceptible and can be carriers of the virus. To understand its pathogenesis, tissue and cellular tropisms of VHSV in larval and juvenile Pacific herring were investigated with immunohistochemistry, transmission electron microscopy, and viral tissue titer. In larval herring, early viral tropism for epithelial tissues (6d post-exposure) was indicated by foci of epidermal thickening that contained heavy concentrations of virus. This was followed by a cellular tropism for fibroblasts within the fin bases and the dermis, but expanded to cells of the kidney, liver, pancreas, gastrointestinal tract and meninges in the brain. Among wild juvenile herring that underwent a VHS epizootic in the laboratory, the disease was characterized by acute and chronic phases of death. Fish that died during the acute phase had systemic infections in tissues including the submucosa of the gastrointestinal tract, spleen, kidney, liver, and meninges. The disease then transitioned into a chronic phase that was characterized by the appearance of neurological signs including erratic and corkscrew swimming and darkening of the dorsal skin. During the chronic phase viral persistence occurred in nervous tissues including meninges and brain parenchymal cells and in one case in peripheral nerves, while virus was mostly cleared from the other tissues. The results demonstrate the varying VHSV tropisms dependent on the timing of infection and the importance of neural tissues for the persistence and perpetuation of chronic infections in Pacific herring.

  4. Nonsteroidal Anti-Inflammatory Drug without Antibiotics for Acute Viral Infection Increases the Empyema Risk in Children: A Matched Case-Control Study.

    Science.gov (United States)

    Le Bourgeois, Muriel; Ferroni, Agnès; Leruez-Ville, Marianne; Varon, Emmanuelle; Thumerelle, Caroline; Brémont, François; Fayon, Michael J; Delacourt, Christophe; Ligier, Caroline; Watier, Laurence; Guillemot, Didier

    2016-08-01

    To investigate the risk factors of empyema after acute viral infection and to clarify the hypothesized association(s) between empyema and some viruses and/or the use of nonsteroidal anti-inflammatory drugs (NSAIDs). A case-control study was conducted in 15 centers. Cases and controls were enrolled for a source population of children 3-15 years of age with acute viral infections between 2006 and 2009. Among 215 empyemas, 83 cases (children with empyema and acute viral infection within the 15 preceding days) were included, and 83 controls (children with acute viral infection) were matched to cases. Considering the intake of any drug within 72 hours after acute viral infection onset and at least 6 consecutive days of antibiotic use and at least 1 day of NSAIDs exposure, the multivariable analysis retained an increased risk of empyema associated with NSAIDs exposure (aOR 2.79, 95% CI 1.4-5.58, P = .004), and a decreased risk associated with antibiotic use (aOR 0.32, 95% CI 0.11-0.97, P = .04). The risk of empyema associated with NSAIDs exposure was greater for children not prescribed an antibiotic and antibiotic intake diminished that risk for children given NSAIDs. NSAIDs use during acute viral infection is associated with an increased risk of empyema in children, and antibiotics are associated with a decreased risk. The presence of antibiotic-NSAIDs interaction with this risk is suggested. These findings suggest that NSAIDs should not be recommended as a first-line antipyretic treatment during acute viral infections in children. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Viral infection of the marine alga Emiliania huxleyi triggers lipidome remodeling and induces the production of highly saturated triacylglycerol.

    Science.gov (United States)

    Malitsky, Sergey; Ziv, Carmit; Rosenwasser, Shilo; Zheng, Shuning; Schatz, Daniella; Porat, Ziv; Ben-Dor, Shifra; Aharoni, Asaph; Vardi, Assaf

    2016-04-01

    Viruses that infect marine photosynthetic microorganisms are major ecological and evolutionary drivers of microbial food webs, estimated to turn over more than a quarter of the total photosynthetically fixed carbon. Viral infection of the bloom-forming microalga Emiliania huxleyi induces the rapid remodeling of host primary metabolism, targeted towards fatty acid metabolism. We applied a liquid chromatography-mass spectrometry (LC-MS)-based lipidomics approach combined with imaging flow cytometry and gene expression profiling to explore the impact of viral-induced metabolic reprogramming on lipid composition. Lytic viral infection led to remodeling of the cellular lipidome, by predominantly inducing the biosynthesis of highly saturated triacylglycerols (TAGs), coupled with a significant accumulation of neutral lipids within lipid droplets. Furthermore, TAGs were found to be a major component (77%) of the lipidome of isolated virions. Interestingly, viral-induced TAGs were significantly more saturated than TAGs produced under nitrogen starvation. This study highlights TAGs as major products of the viral-induced metabolic reprogramming during the host-virus interaction and indicates a selective mode of membrane recruitment during viral assembly, possibly by budding of the virus from specialized subcellular compartments. These findings provide novel insights into the role of viruses infecting microalgae in regulating metabolism and energy transfer in the marine environment and suggest their possible biotechnological application in biofuel production. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  6. Identification of viral infections in the prostate and evaluation of their association with cancer

    Directory of Open Access Journals (Sweden)

    Calderon-Cardenas German

    2010-06-01

    Full Text Available Abstract Background Several viruses with known oncogenic potential infect prostate tissue, among these are the polyomaviruses BKV, JCV, and SV40; human papillomaviruses (HPVs, and human cytomegalovirus (HCMV infections. Recently, the Xenotropic Murine Leukemia Virus-related gammaretrovirus (XMRV was identified in prostate tissue with a high prevalence observed in prostate cancer (PC patients homozygous for the glutamine variant of the RNASEL protein (462Q/Q. Association studies with the R462Q allele and non-XMRV viruses have not been reported. We assessed associations between prostate cancer, prostate viral infections, and the RNASEL 462Q allele in Mexican cancer patients and controls. Methods 130 subjects (55 prostate cancer cases and 75 controls were enrolled in the study. DNA and RNA isolated from prostate tissues were screened for the presence of viral genomes. Genotyping of the RNASEL R462Q variant was performed by Taqman method. Results R/R, R/Q, and Q/Q frequencies for R462Q were 0.62, 0.38, and 0.0 for PC cases and 0.69, 0.24, and 0.07 for controls, respectively. HPV sequences were detected in 11 (20.0% cases and 4 (5.3% controls. XMRV and HCMV infections were detected in one and six control samples, respectively. The risk of PC was significantly increased (Odds Ratio = 3.98; 95% CI: 1.17-13.56, p = 0.027 by infection of the prostatic tissue with HPV. BKV, JCV, and SV40 sequences were not detected in any of the tissue samples examined. Conclusions We report a positive association between PC and HPV infection. The 462Q/Q RNASEL genotype was not represented in our PC cases; thus, its interaction with prostate viral infections and cancer could not be evaluated.

  7. Roles of African swine fever virus structural proteins in viral infection

    Directory of Open Access Journals (Sweden)

    Jia Ning

    2017-06-01

    Full Text Available African swine fever virus (ASFV is a large, double-stranded DNA virus and the sole member of the Asfarviridae family. ASFV infects domestic pigs, wild boars, warthogs, and bush pigs, as well as soft ticks (Ornithodoros erraticus, which likely act as a vector. The major target is swine monocyte-macrophage cells. The virus can cause high fever, haemorrhagic lesions, cyanosis, anorexia, and even fatalities in domestic pigs. Currently, there is no vaccine and effective disease control strategies against its spread are culling infected pigs and maintaining high biosecurity standards. African swine fever (ASF spread to Europe from Africa in the middle of the 20th century, and later also to South America and the Caribbean. Since then, ASF has spread more widely and thus is still a great challenge for swine breeding. The genome of ASFV ranges in length from about 170 to 193 kbp depending on the isolate and contains between 150 and 167 open reading frames (ORFs. The ASFV genome encodes 150 to 200 proteins, around 50 of them structural. The roles of virus structural proteins in viral infection have been described. These proteins, such as pp220, pp62, p72, p54, p30, and CD2v, serve as the major component of virus particles and have roles in attachment, entry, and replication. All studies on ASFV proteins lay a good foundation upon which to clarify the infection mechanism and develop vaccines and diagnosis methods. In this paper, the roles of ASFV structural proteins in viral infection are reviewed.

  8. Role of viral infection in the etiopathogenesis of breast cancer

    Directory of Open Access Journals (Sweden)

    L. A. Ashrafyan

    2010-01-01

    Full Text Available The viral nature of many female genital cancers is now beyond question; however, the role of viral infection in the pathogenesis of breast cancer (BC has not been adequately investigated. The paper defines the importance of a number of viruses in the etiopathogenesis of on- cogynecological diseases. It presents the results of examining 60 patients with Stages I-IV BC and 30 patients with fibrocystic mastopathy, in whom the presence of DNA-containing virus genomes in tumor tissue was compared, and the data of polymerase chain reaction study of genital tract smears. It is shown that human papillomaviruses and cytomegaloviruses do not play a fundamental role in the develop- ment of BC; there is no valid evidence for Epstein–Barr virus.

  9. Deciphering the role of DC subsets in MCMV infection to better understand immune protection against viral infections

    Directory of Open Access Journals (Sweden)

    Marc eDALOD

    2014-07-01

    Full Text Available Infection of mice with murine cytomegalovirus (MCMV recapitulates many physiopathological characteristics of human CMV infection and enables studying the interactions between a virus and its natural host. Dendritic cells (DC are mononuclear phagocytes linking innate and adaptive immunity which are both necessary for MCMV control. DC are critical for the induction of cellular immunity because they are uniquely efficient for the activation of naïve T cells during their first encounter with a pathogen. DC are equipped with a variety of innate immune recognition receptors (I2R2 allowing them to detect pathogens or infections and to engulf molecules, microorganisms or cellular debris. The combinatorial engagement of I2R2 during infections controls DC maturation and shapes their response in terms of cytokine production, activation of natural killer (NK cells and functional polarization of T cells. Several DC subsets exist which express different arrays of I2R2 and are specialized in distinct functions. The study of MCMV infection helped deciphering the physiological roles of DC subsets and their molecular regulation. It allowed the identification and first in vivo studies of mouse plasmacytoid DC which produce high level of interferons-α/β early after infection. Despite its ability to infect DC and dampen their functions, MCMV induces very robust, efficient and long-lasting CD8 T cell responses. Their priming may rely on the unique ability of uninfected XCR1+ DC to cross-present engulfed viral antigens and thus to counter MCMV interference with antigen presentation. A balance appears to have been reached during co-evolution, allowing controlled replication of the virus for horizontal spread without pathological consequences for the immunocompetent host. We will discuss the role of the interplay between the virus and DC in setting this balance, and how advancing this knowledge further could help develop better vaccines against other intracellular

  10. The composition of the gut microbiota throughout life, with an emphasis on early life

    Directory of Open Access Journals (Sweden)

    Juan Miguel Rodríguez

    2015-02-01

    Full Text Available The intestinal microbiota has become a relevant aspect of human health. Microbial colonization runs in parallel with immune system maturation and plays a role in intestinal physiology and regulation. Increasing evidence on early microbial contact suggest that human intestinal microbiota is seeded before birth. Maternal microbiota forms the first microbial inoculum, and from birth, the microbial diversity increases and converges toward an adult-like microbiota by the end of the first 3–5 years of life. Perinatal factors such as mode of delivery, diet, genetics, and intestinal mucin glycosylation all contribute to influence microbial colonization. Once established, the composition of the gut microbiota is relatively stable throughout adult life, but can be altered as a result of bacterial infections, antibiotic treatment, lifestyle, surgical, and a long-term change in diet. Shifts in this complex microbial system have been reported to increase the risk of disease. Therefore, an adequate establishment of microbiota and its maintenance throughout life would reduce the risk of disease in early and late life. This review discusses recent studies on the early colonization and factors influencing this process which impact on health.

  11. The composition of the gut microbiota throughout life, with an emphasis on early life

    Science.gov (United States)

    Rodríguez, Juan Miguel; Murphy, Kiera; Stanton, Catherine; Ross, R. Paul; Kober, Olivia I.; Juge, Nathalie; Avershina, Ekaterina; Rudi, Knut; Narbad, Arjan; Jenmalm, Maria C.; Marchesi, Julian R.; Collado, Maria Carmen

    2015-01-01

    The intestinal microbiota has become a relevant aspect of human health. Microbial colonization runs in parallel with immune system maturation and plays a role in intestinal physiology and regulation. Increasing evidence on early microbial contact suggest that human intestinal microbiota is seeded before birth. Maternal microbiota forms the first microbial inoculum, and from birth, the microbial diversity increases and converges toward an adult-like microbiota by the end of the first 3–5 years of life. Perinatal factors such as mode of delivery, diet, genetics, and intestinal mucin glycosylation all contribute to influence microbial colonization. Once established, the composition of the gut microbiota is relatively stable throughout adult life, but can be altered as a result of bacterial infections, antibiotic treatment, lifestyle, surgical, and a long-term change in diet. Shifts in this complex microbial system have been reported to increase the risk of disease. Therefore, an adequate establishment of microbiota and its maintenance throughout life would reduce the risk of disease in early and late life. This review discusses recent studies on the early colonization and factors influencing this process which impact on health. PMID:25651996

  12. Chromatinization of the KSHV Genome During the KSHV Life Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Uppal, Timsy [Department of Microbiology and Immunology, School of Medicine, University of Nevada, 1664 N Virginia Street, MS 320, Reno, NV 89557 (United States); Jha, Hem C. [Department of Microbiology and the Tumor Virology Program of the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104 (United States); Verma, Subhash C. [Department of Microbiology and Immunology, School of Medicine, University of Nevada, 1664 N Virginia Street, MS 320, Reno, NV 89557 (United States); Robertson, Erle S., E-mail: erle@mail.med.upenn.edu [Department of Microbiology and the Tumor Virology Program of the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104 (United States)

    2015-01-14

    Kaposi’s sarcoma-associated herpesvirus (KSHV) belongs to the gamma herpesvirus family and is the causative agent of various lymphoproliferative diseases in humans. KSHV, like other herpesviruses, establishes life-long latent infection with the expression of a limited number of viral genes. Expression of these genes is tightly regulated by both the viral and cellular factors. Recent advancements in identifying the expression profiles of viral transcripts, using tilling arrays and next generation sequencing have identified additional coding and non-coding transcripts in the KSHV genome. Determining the functions of these transcripts will provide a better understanding of the mechanisms utilized by KSHV in altering cellular pathways involved in promoting cell growth and tumorigenesis. Replication of the viral genome is critical in maintaining the existing copies of the viral episomes during both latent and lytic phases of the viral life cycle. The replication of the viral episome is facilitated by viral components responsible for recruiting chromatin modifying enzymes and replication factors for altering the chromatin complexity and replication initiation functions, respectively. Importantly, chromatin modification of the viral genome plays a crucial role in determining whether the viral genome will persist as latent episome or undergo lytic reactivation. Additionally, chromatinization of the incoming virion DNA, which lacks chromatin structure, in the target cells during primary infection, helps in establishing latent infection. Here, we discuss the recent advancements on our understating of KSHV genome chromatinization and the consequences of chromatin modifications on viral life cycle.

  13. Chromatinization of the KSHV Genome During the KSHV Life Cycle

    International Nuclear Information System (INIS)

    Uppal, Timsy; Jha, Hem C.; Verma, Subhash C.; Robertson, Erle S.

    2015-01-01

    Kaposi’s sarcoma-associated herpesvirus (KSHV) belongs to the gamma herpesvirus family and is the causative agent of various lymphoproliferative diseases in humans. KSHV, like other herpesviruses, establishes life-long latent infection with the expression of a limited number of viral genes. Expression of these genes is tightly regulated by both the viral and cellular factors. Recent advancements in identifying the expression profiles of viral transcripts, using tilling arrays and next generation sequencing have identified additional coding and non-coding transcripts in the KSHV genome. Determining the functions of these transcripts will provide a better understanding of the mechanisms utilized by KSHV in altering cellular pathways involved in promoting cell growth and tumorigenesis. Replication of the viral genome is critical in maintaining the existing copies of the viral episomes during both latent and lytic phases of the viral life cycle. The replication of the viral episome is facilitated by viral components responsible for recruiting chromatin modifying enzymes and replication factors for altering the chromatin complexity and replication initiation functions, respectively. Importantly, chromatin modification of the viral genome plays a crucial role in determining whether the viral genome will persist as latent episome or undergo lytic reactivation. Additionally, chromatinization of the incoming virion DNA, which lacks chromatin structure, in the target cells during primary infection, helps in establishing latent infection. Here, we discuss the recent advancements on our understating of KSHV genome chromatinization and the consequences of chromatin modifications on viral life cycle

  14. Active and separate secretion of fiber and penton base during the early phase of Ad2 or Ad5 infection

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Yuhua; Zhang, Bo; Hou, Weihong; Lin, Hongyu [Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing (China); Rebetz, Johan [The Rausing Laboratory, Department of Neurosurgery, Lund University, Lund (Sweden); Hong, Saw-See [Viral Infections & Comparative Pathology, UMR-754 UCBL-INRA-EPHE, Université Lyon 1, Lyon Cedex 07 (France); Wang, Youjun; Ran, Liang [Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing (China); Fan, Xiaolong, E-mail: XFan@bnu.edu.cn [Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing (China)

    2017-05-15

    Fiber and penton base overproduced in adenovirus (Ad) infected cells can be secreted prior to progeny release and thereby regulate progeny spread. We aimed to investigate the mechanisms of fiber and penton base secretion in Ad2- or Ad5-infected A549 cells. Our flow cytometry analyses detected abundant surface fiber molecules, but little penton base molecules at 12 h post infection. Immunogold staining combined with transmission electron microscopic analyses revealed separate, non-co-localized release of fiber and penton base in the proximity of the plasma membrane. Depolymerization of microtubule and actin cytoskeletons, and inhibition of Rock kinase and myosin II activity together demonstrated cytoskeletal network-dependent fiber secretion. Inhibition of intracellular calcium [Ca{sup 2+}]{sub i} signaling caused diminished fiber secretion, which was associated with diminished progeny production. Thus, fiber and penton base are actively and separately secreted during the early stages of Ad2 or Ad5 infection, their secretion may play important role in Ad life cycle. - Highlights: •Excessive production of structural proteins is common to viral infection, which may regulate the host-virus equilibrium and the spreading of viruses. •The adenovirus (Ad) structural proteins, fiber and penton base, are respectively important for Ad binding to its receptor and subsequent internalization in host cells. In Ad infected cells, these two structural proteins are excessively produced. •The mechanisms underlying the release of fiber and penton base molecules at the early phase of Ad infection is yet poorly understood. •Our studies show that in Ad5 or Ad2 infected A549 cells, fiber and penton base molecules are actively and separately secreted. •Fiber secretion is dependent on cytoskeleton-mediated protein traffic. •Inhibition of myosin II motor and Ca{sup 2+} signaling activity significantly diminishes fiber secretion. •These findings could contribute to our

  15. Active and separate secretion of fiber and penton base during the early phase of Ad2 or Ad5 infection

    International Nuclear Information System (INIS)

    Yan, Yuhua; Zhang, Bo; Hou, Weihong; Lin, Hongyu; Rebetz, Johan; Hong, Saw-See; Wang, Youjun; Ran, Liang; Fan, Xiaolong

    2017-01-01

    Fiber and penton base overproduced in adenovirus (Ad) infected cells can be secreted prior to progeny release and thereby regulate progeny spread. We aimed to investigate the mechanisms of fiber and penton base secretion in Ad2- or Ad5-infected A549 cells. Our flow cytometry analyses detected abundant surface fiber molecules, but little penton base molecules at 12 h post infection. Immunogold staining combined with transmission electron microscopic analyses revealed separate, non-co-localized release of fiber and penton base in the proximity of the plasma membrane. Depolymerization of microtubule and actin cytoskeletons, and inhibition of Rock kinase and myosin II activity together demonstrated cytoskeletal network-dependent fiber secretion. Inhibition of intracellular calcium [Ca 2+ ] i signaling caused diminished fiber secretion, which was associated with diminished progeny production. Thus, fiber and penton base are actively and separately secreted during the early stages of Ad2 or Ad5 infection, their secretion may play important role in Ad life cycle. - Highlights: •Excessive production of structural proteins is common to viral infection, which may regulate the host-virus equilibrium and the spreading of viruses. •The adenovirus (Ad) structural proteins, fiber and penton base, are respectively important for Ad binding to its receptor and subsequent internalization in host cells. In Ad infected cells, these two structural proteins are excessively produced. •The mechanisms underlying the release of fiber and penton base molecules at the early phase of Ad infection is yet poorly understood. •Our studies show that in Ad5 or Ad2 infected A549 cells, fiber and penton base molecules are actively and separately secreted. •Fiber secretion is dependent on cytoskeleton-mediated protein traffic. •Inhibition of myosin II motor and Ca 2+ signaling activity significantly diminishes fiber secretion. •These findings could contribute to our understanding of Ad

  16. Hepatitis A, B and C viral co-infections among HIV-infected adults presenting for care and treatment at Muhimbili National Hospital in Dar es Salaam, Tanzania

    Directory of Open Access Journals (Sweden)

    Matee Mecky

    2008-12-01

    Full Text Available Abstract Background Tanzania is currently scaling-up access to anti-retro viral therapy (ART to reach as many eligible persons as possible. Hepatitis viral co-infections are known to influence progression, management as well as outcome of HIV infection. However, information is scarce regarding the prevalence and predictors of viral hepatitis co-infection among HIV-infected individuals presenting at the HIV care and treatment clinics in the country. Methods A cross-sectional study conducted between April and September 2006 enrolled 260 HIV-1 infected, HAART naïve patients aged ≥18 years presenting at the HIV care and treatment clinic (CTC of the Muhimbili National Hospital (MNH. The evaluation included clinical assessment and determination of CD4+ T-lymphocyte count, serum transaminases and serology for Hepatitis A, B and C markers by ELISA. Results The prevalence of anti HAV IgM, HBsAg, anti-HBc IgM and anti-HCV IgG antibodies were 3.1%, 17.3%, 2.3% and 18.1%, respectively. Dual co-infection with HBV and HCV occurred in 10 individuals (3.9%, while that of HAV and HBV was detected in two subjects (0.8%. None of the patients had all the three hepatitis viruses. Most patients (81.1% with hepatitis co-infection neither had specific clinical features nor raised serum transaminases. History of blood transfusion and jaundice were independent predictors for HBsAg and anti-HBc IgM positivity, respectively. Conclusion There is high prevalence of markers for hepatitis B and C infections among HIV infected patients seeking care and treatment at MNH. Clinical features and a raise in serum alanine aminotransferase were of limited predictive values for the viral co-infections. Efforts to scale up HAART should also address co-infections with Hepatitis B and C viruses.

  17. Viral Small-RNA Analysis of Bombyx mori Larval Midgut during Persistent and Pathogenic Cytoplasmic Polyhedrosis Virus Infection

    OpenAIRE

    Zografidis, Aris; Van Nieuwerburgh, Filip; Kolliopoulou, Anna; Apostolou-Karampelis, Konstantinos; Head, Steven R.; Deforce, Dieter; Smagghe, Guy; Swevers, Luc

    2015-01-01

    The lepidopteran innate immune response against RNA viruses remains poorly understood, while in other insects several studies have highlighted an essential role for the exo-RNAi pathway in combating viral infection. Here, by using deep-sequencing technology for viral small-RNA (vsRNA) assessment, we provide evidence that exo-RNAi is operative in the silkworm Bombyx mori against both persistent and pathogenic infection of B. mori cytoplasmic polyhedrosis virus (BmCPV) which is characterized by...

  18. Risk of early-onset neonatal infection with maternal infection or colonization: a global systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Grace J Chan

    2013-08-01

    Full Text Available Neonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period.We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4% were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9-11.2. Newborns of mothers with colonization had a 9.4 (95% CI 3.1-28.5 times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM had a 2.3 (95% CI 1.0-5.4 times higher odds of infection than newborns of mothers without risk factors.Neonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high neonatal mortality, are needed to

  19. Inhibition of Nipah virus infection in vivo: targeting an early stage of paramyxovirus fusion activation during viral entry.

    Directory of Open Access Journals (Sweden)

    Matteo Porotto

    2010-10-01

    Full Text Available In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viral and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses.

  20. Lower Self-Reported Quality of Life in HIV-Infected Patients on cART and With Low Comorbidity Compared With Healthy Controls

    DEFF Research Database (Denmark)

    Pedersen, Karin K; Eiersted, Morten R; Gaardbo, Julie C

    2015-01-01

    replication and with low comorbidity, compared with healthy controls. We furthermore aimed to identify factors associated with QoL. DESIGN AND METHODS: Cross-sectional study of 52 HIV-infected patients and 23 healthy controls matched on age, gender, education, and comorbidity. HIV-infected patients...... and healthy controls had previously been examined regarding cognitive, physical, metabolic, and immunological parameters. QoL was investigated using the Medical Outcomes Study HIV Health Survey (MOS-HIV). Linear multiple regression models were created to find factors associated with mental health summary......BACKGROUND: Self-reported quality of life (QoL) has previously been found to be impaired in patients living with HIV and associated with viral replication, degree of immunodeficiency, and comorbidity. We aimed at investigating QoL in a group of HIV-infected patients with suppressed viral...

  1. Detection of Vero Cells Infected with Herpes Simplex Types 1 and 2 and Varicella Zoster Viruses Using Raman Spectroscopy and Advanced Statistical Methods.

    Science.gov (United States)

    Huleihel, Mahmoud; Shufan, Elad; Zeiri, Leila; Salman, Ahmad

    2016-01-01

    Of the eight members of the herpes family of viruses, HSV1, HSV2, and varicella zoster are the most common and are mainly involved in cutaneous disorders. These viruses usually are not life-threatening, but in some cases they might cause serious infections to the eyes and the brain that can lead to blindness and possibly death. An effective drug (acyclovir and its derivatives) is available against these viruses. Therefore, early detection and identification of these viral infections is highly important for an effective treatment. Raman spectroscopy, which has been widely used in the past years in medicine and biology, was used as a powerful spectroscopic tool for the detection and identification of these viral infections in cell culture, due to its sensitivity, rapidity and reliability. Our results showed that it was possible to differentiate, with a 97% identification success rate, the uninfected Vero cells that served as a control, from the Vero cells that were infected with HSV-1, HSV-2, and VZV. For that, linear discriminant analysis (LDA) was performed on the Raman spectra after principal component analysis (PCA) with a leave one out (LOO) approach. Raman spectroscopy in tandem with PCA and LDA enable to differentiate among the different herpes viral infections of Vero cells in time span of few minutes with high accuracy rate. Understanding cell molecular changes due to herpes viral infections using Raman spectroscopy may help in early detection and effective treatment.

  2. Detection of Vero Cells Infected with Herpes Simplex Types 1 and 2 and Varicella Zoster Viruses Using Raman Spectroscopy and Advanced Statistical Methods.

    Directory of Open Access Journals (Sweden)

    Mahmoud Huleihel

    Full Text Available Of the eight members of the herpes family of viruses, HSV1, HSV2, and varicella zoster are the most common and are mainly involved in cutaneous disorders. These viruses usually are not life-threatening, but in some cases they might cause serious infections to the eyes and the brain that can lead to blindness and possibly death. An effective drug (acyclovir and its derivatives is available against these viruses. Therefore, early detection and identification of these viral infections is highly important for an effective treatment. Raman spectroscopy, which has been widely used in the past years in medicine and biology, was used as a powerful spectroscopic tool for the detection and identification of these viral infections in cell culture, due to its sensitivity, rapidity and reliability. Our results showed that it was possible to differentiate, with a 97% identification success rate, the uninfected Vero cells that served as a control, from the Vero cells that were infected with HSV-1, HSV-2, and VZV. For that, linear discriminant analysis (LDA was performed on the Raman spectra after principal component analysis (PCA with a leave one out (LOO approach. Raman spectroscopy in tandem with PCA and LDA enable to differentiate among the different herpes viral infections of Vero cells in time span of few minutes with high accuracy rate. Understanding cell molecular changes due to herpes viral infections using Raman spectroscopy may help in early detection and effective treatment.

  3. Iron Overload Is Associated With Oxidative Stress and Nutritional Immunity During Viral Infection in Fish.

    Science.gov (United States)

    Tarifeño-Saldivia, Estefanía; Aguilar, Andrea; Contreras, David; Mercado, Luis; Morales-Lange, Byron; Márquez, Katherine; Henríquez, Adolfo; Riquelme-Vidal, Camila; Boltana, Sebastian

    2018-01-01

    Iron is a trace element, essential to support life due to its inherent ability to exchange electrons with a variety of molecules. The use of iron as a cofactor in basic metabolic pathways is essential to both pathogenic microorganisms and their hosts. During evolution, the shared requirement of micro- and macro-organisms for this important nutrient has shaped the pathogen-host relationship. Infectious pancreatic necrosis virus (IPNv) affects salmonids constituting a sanitary problem for this industry as it has an important impact on post-smolt survival. While immune modulation induced by IPNv infection has been widely characterized on Salmo salar , viral impact on iron host metabolism has not yet been elucidated. In the present work, we evaluate short-term effect of IPNv on several infected tissues from Salmo salar . We observed that IPNv displayed high tropism to headkidney, which directly correlates with a rise in oxidative stress and antiviral responses. Transcriptional profiling on headkidney showed a massive modulation of gene expression, from which biological pathways involved with iron metabolism were remarkable. Our findings suggest that IPNv infection increase oxidative stress on headkidney as a consequence of iron overload induced by a massive upregulation of genes involved in iron metabolism.

  4. Hepatitis B viral infection with nephrotic syndrome treated with lamivudine.

    Science.gov (United States)

    Banu, N A; Khatoon, S; Quadir, E; Rahman, M M; Khan, M A

    2007-07-01

    A 04 years old boy with 02 months history of generalized oedema and scanty micturition was diagnosed as nephrotic syndrome with hepatitis B viral infection. He had evidence of active viral replication. After 01 month treatment with oral lamivudine, his urine became protein free and after 04 months, he had seroconversion from HBeAg+ve to HBeAg-ve. Lamivudine was continued for 01 year. He had no relapse after discontinuation of therapy and remained well after 36 months of completion of therapy. He had no evidence of active viral replication during this period, however HBsAg remained positive indication carrier state. As most children with HBV associated nephropathy have no evidence of chronic hepatitis, all such children must undergo HBV screening and for chronic liver disease if HBV screening is positive. As such children do not respond to prednisolone or other immunosuppresive therapy which might harm them, antiviral therapy should be considered. Lamivudine is a suitable alternative to IFN alpha owing to its low cost, ease of administration and fewer side effects.

  5. TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection.

    Science.gov (United States)

    Maru, Saumya; Jin, Ge; Schell, Todd D; Lukacher, Aron E

    2017-04-01

    Establishing functional tissue-resident memory (TRM) cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV) variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells. Using this strategy, we found that antigen stimulation strength was inversely associated with the function of memory CD8 T cells during a persistent viral infection. We further show that CD8 TRM cells recruited to the brain following systemic infection with viruses expressing epitopes with suboptimal stimulation strength respond more efficiently to challenge CNS infection with virus expressing cognate antigen. These data demonstrate that the strength of antigenic stimulation during recruitment of CD8 T cells influences the functional integrity of TRM cells in a persistent viral infection.

  6. Early-Life Nutritional Programming of Health and Disease in The Gambia.

    Science.gov (United States)

    Moore, Sophie E

    2017-01-01

    Exposures during early life are increasingly being recognised as factors that play an important role in the aetiology of chronic non-communicable diseases (NCDs). The "Developmental Origins of Health and Disease" (DOHaD) hypothesis asserts that adverse early-life exposures - most notably unbalanced nutrition - leads to an increased risk for a range of NCDs and that disease risk is highest when there is a "mismatch" between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in settings undergoing a rapid nutrition transition. We investigated the link between early-life nutritional exposures and long-term health in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomised controlled trials of nutritional supplementation in pregnancy, and the "experiment of nature" that seasonality in this region provides, we investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs. Key Messages: Our work in rural Gambia suggests that in populations with high rates of under-nutrition in early life, the immune system may be sensitive to nutritional deficiencies early in life, resulting in a greater susceptibility to infection-related morbidity and mortality. © 2017 S. Karger AG, Basel.

  7. CRISPR-Cas type I-A Cascade complex couples viral infection surveillance to host transcriptional regulation in the dependence of Csa3b

    Science.gov (United States)

    He, Fei; Vestergaard, Gisle; Peng, Wenfang; She, Qunxin

    2017-01-01

    Abstract CRISPR-Cas (clustered regularly interspaced short palindromic repeats and the associated genes) constitute adaptive immune systems in bacteria and archaea and they provide sequence specific immunity against foreign nucleic acids. CRISPR-Cas systems are activated by viral infection. However, little is known about how CRISPR-Cas systems are activated in response to viral infection or how their expression is controlled in the absence of viral infection. Here, we demonstrate that both the transcriptional regulator Csa3b, and the type I-A interference complex Cascade, are required to transcriptionally repress the interference gene cassette in the archaeon Sulfolobus. Csa3b binds to two palindromic repeat sites in the promoter region of the cassette and facilitates binding of the Cascade to the promoter region. Upon viral infection, loading of Cascade complexes onto crRNA-matching protospacers leads to relief of the transcriptional repression. Our data demonstrate a mechanism coupling CRISPR-Cas surveillance of protospacers to transcriptional regulation of the interference gene cassette thereby allowing a fast response to viral infection. PMID:27980065

  8. Small Interfering RNA Pathway Modulates Initial Viral Infection in Midgut Epithelium of Insect after Ingestion of Virus.

    Science.gov (United States)

    Lan, Hanhong; Chen, Hongyan; Liu, Yuyan; Jiang, Chaoyang; Mao, Qianzhuo; Jia, Dongsheng; Chen, Qian; Wei, Taiyun

    2016-01-15

    Numerous viruses are transmitted in a persistent manner by insect vectors. Persistent viruses establish their initial infection in the midgut epithelium, from where they disseminate to the midgut visceral muscles. Although propagation of viruses in insect vectors can be controlled by the small interfering RNA (siRNA) antiviral pathway, whether the siRNA pathway can control viral dissemination from the midgut epithelium is unknown. Infection by a rice virus (Southern rice black streaked dwarf virus [SRBSDV]) of its incompetent vector (the small brown planthopper [SBPH]) is restricted to the midgut epithelium. Here, we show that the siRNA pathway is triggered by SRBSDV infection in continuously cultured cells derived from the SBPH and in the midgut of the intact insect. Knockdown of the expression of the core component Dicer-2 of the siRNA pathway by RNA interference strongly increased the ability of SRBSDV to propagate in continuously cultured SBPH cells and in the midgut epithelium, allowing viral titers in the midgut epithelium to reach the threshold (1.99 × 10(9) copies of the SRBSDV P10 gene/μg of midgut RNA) needed for viral dissemination into the SBPH midgut muscles. Our results thus represent the first elucidation of the threshold for viral dissemination from the insect midgut epithelium. Silencing of Dicer-2 further facilitated the transmission of SRBSDV into rice plants by SBPHs. Taken together, our results reveal the new finding that the siRNA pathway can control the initial infection of the insect midgut epithelium by a virus, which finally affects the competence of the virus's vector. Many viral pathogens that cause significant global health and agricultural problems are transmitted via insect vectors. The first bottleneck in viral infection, the midgut epithelium, is a principal determinant of the ability of an insect species to transmit a virus. Southern rice black streaked dwarf virus (SRBSDV) is restricted exclusively to the midgut epithelium of an

  9. Heat shock protein 90 positively regulates Chikungunya virus replication by stabilizing viral non-structural protein nsP2 during infection.

    Directory of Open Access Journals (Sweden)

    Indrani Das

    Full Text Available BACKGROUND: The high morbidity and socio-economic loss associated with the recent massive global outbreak of Chikungunya virus (CHIKV emphasize the need to understand the biology of the virus for developing effective antiviral therapies. METHODS AND FINDINGS: In this study, an attempt was made to understand the molecular mechanism involved in Heat shock protein 90 (Hsp90 mediated regulation of CHIKV infection in mammalian cells using CHIKV prototype strain (S 27 and Indian outbreak strain of 2006 (DRDE-06. Our results showed that Hsp90 is required at a very early stage of viral replication and Hsp90 inhibitor Geldanamycin (GA can abrogate new virus particle formation more effectively in the case of S 27 than that of DRDE-06. Further analysis revealed that CHIKV nsP2 protein level is specifically reduced by GA treatment as well as HSP90-siRNA transfection; however, viral RNA remains unaltered. Immunoprecipitation analysis showed that nsP2 interacts with Hsp90 during infection; however this interaction is reduced in the presence of GA. In addition, our analysis on Hsp90 associated PI3K/Akt/mTOR signaling pathway demonstrated that CHIKV infection stabilizes Raf1 and activates Hsp90 client protein Akt, which in turn phosphorylates mTOR. Subsequently, this phosphorylation leads to the activation of two important downstream effectors, S6K and 4EBP1, which may facilitate translation of viral as well as cellular mRNAs. Hence, the data suggests that CHIKV infection is regulated by Hsp90 associated Akt phosphorylation and DRDE-06 is more efficient than S 27 in enhancing the activation of host signaling molecules for its efficient replication and virus production. CONCLUSION: Hsp90 positively regulates Chikungunya virus replication by stabilizing CHIKV-nsP2 through its interaction during infection. The study highlights the possible molecular mechanism of GA mediated inhibition of CHIKV replication and differential effect of this drug on S 27 and DRDE-06

  10. Viral-Associated GN: Hepatitis C and HIV.

    Science.gov (United States)

    Kupin, Warren L

    2017-08-07

    Viruses are capable of inducing a wide spectrum of glomerular disorders that can be categorized on the basis of the duration of active viremia: acute, subacute, or chronic. The variable responses of the adaptive immune system to each time period of viral infection results mechanistically in different histologic forms of glomerular injury. The unique presence of a chronic viremic carrier state with either hepatitis C (HCV) or HIV has led to the opportunity to study in detail various pathogenic mechanisms of viral-induced glomerular injury, including direct viral infection of renal tissue and the development of circulating immune complexes composed of viral antigens that deposit along the glomerular basement membrane. Epidemiologic data show that approximately 25%-30% of all HIV patients are coinfected with HCV and 5%-10% of all HCV patients are coinfected with HIV. This situation can often lead to a challenging differential diagnosis when glomerular disease occurs in this dual-infected population and requires the clinician to be familiar with the clinical presentation, laboratory workup, and pathophysiology behind the development of renal disease for both HCV and HIV. Both of these viruses can be categorized under the new classification of infection-associated GN as opposed to being listed as causes of postinfectious GN as has previously been applied to them. Neither of these viruses lead to renal injury after a latent period of controlled and inactive viremia. The geneses of HCV- and HIV-associated glomerular diseases share a total dependence on the presence of active viral replication to sustain renal injury so the renal disease cannot be listed under "postinfectious" GN. With the new availability of direct-acting antivirals for HCV and more effective combined antiretroviral therapy for HIV, successful remission and even regression of glomerular lesions can be achieved if initiated at an early stage. Copyright © 2017 by the American Society of Nephrology.

  11. Viral infection of implanted meningeal tumors induces antitumor memory T-cells to travel to the brain and eliminate established tumors.

    Science.gov (United States)

    Gao, Yanhua; Whitaker-Dowling, Patricia; Barmada, Mamdouha A; Basse, Per H; Bergman, Ira

    2015-04-01

    Leptomeningeal metastases occur in 2%-5% of patients with breast cancer and have an exceptionally poor prognosis. The blood-brain and blood-meningeal barriers severely inhibit successful chemotherapy. We have developed a straightforward method to induce antitumor memory T-cells using a Her2/neu targeted vesicular stomatitis virus. We sought to determine whether viral infection of meningeal tumor could attract antitumor memory T-cells to eradicate the tumors. Meningeal implants in mice were studied using treatment trials and analyses of immune cells in the tumors. This paper demonstrates that there is a blood-meningeal barrier to bringing therapeutic memory T-cells to meningeal tumors. The barrier can be overcome by viral infection of the tumor. Viral infection of the meningeal tumors followed by memory T-cell transfer resulted in 89% cure of meningeal tumor in 2 different mouse strains. Viral infection produced increased infiltration and proliferation of transferred memory T-cells in the meningeal tumors. Following viral infection, the leukocyte infiltration in meninges and tumor shifted from predominantly macrophages to predominantly T-cells. Finally, this paper shows that successful viral therapy of peritoneal tumors generates memory CD8 T-cells that prevent establishment of tumor in the meninges of these same animals. These results support the hypothesis that a virally based immunization strategy can be used to both prevent and treat meningeal metastases. The meningeal barriers to cancer therapy may be much more permeable to treatment based on cells than treatment based on drugs or molecules. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Viral respiratory tract infections among patients with acute undifferentiated fever in Vietnam

    NARCIS (Netherlands)

    Phuong, Hoang Lan; Nga, Tran T. T.; van Doornum, Gerard J.; Groen, Jan; Binh, Tran Q.; Giao, Phan T.; Hung, Le Q.; Nams, Nguyen V.; Kager, P. A.; de Vries, Peter J.

    2010-01-01

    To investigate the proportion of viral respiratory tract infections among acute undifferentiated fevers (AUFs) at primary health facilities in southern Vietnam during 2001-2005, patients with AUF not caused by malaria were enrolled at twelve primary health facilities and a clinic for malaria control

  13. THE ROLE OF INTERFERON ALPHA-2b IN REDUCING OF VIRAL LOAD IN HPV INFECTED WOMEN

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    Кристина Владимировна Марочко

    2017-05-01

    Conclusion. Mono-infection was prevalent among HPV infected women HPV 16 is the most frequently detected hrHPV. The use of the drug interferon alfa-2b in the study group, contributed to viral load reduction.

  14. Dynamics of Viremia in Primary HIV-1 infection in Africans: Insights from Analyses of Host and Viral Correlates

    Science.gov (United States)

    Prentice, Heather A.; Price, Matthew A.; Porter, Travis R.; Cormier, Emmanuel; Mugavero, Michael J.; Kamali, Anatoli; Karita, Etienne; Lakhi, Shabir; Sanders, Eduard J.; Anzala, Omu; Amornkul, Pauli N.; Allen, Susan; Hunter, Eric; Kaslow, Richard A.; Gilmour, Jill; Tang, Jianming

    2014-01-01

    In HIV-1 infection, plasma viral load (VL) has dual implications for pathogenesis and public health. Based on well-known patterns of HIV-1 evolution and immune escape, we hypothesized that VL is an evolving quantitative trait that depends heavily on duration of infection (DOI), demographic features, human leukocyte antigen (HLA) genotypes and viral characteristics. Prospective data from 421 African seroconverters with at least four eligible visits did show relatively steady VL beyond 3 months of untreated infection, but host and viral factors independently associated with cross-sectional and longitudinal VL often varied by analytical approaches and sliding time windows. Specifically, the effects of age, HLA-B*53 and infecting HIV-1 subtypes (A1, C and others) on VL were either sporadic or highly sensitive to time windows. These observations were strengthened by the addition of 111 seroconverters with 2–3 eligible VL results, suggesting that DOI should be a critical parameter in epidemiological and clinical studies. PMID:24418560

  15. L Particles Transmit Viral Proteins from Herpes Simplex Virus 1-Infected Mature Dendritic Cells to Uninfected Bystander Cells, Inducing CD83 Downmodulation.

    Science.gov (United States)

    Heilingloh, Christiane S; Kummer, Mirko; Mühl-Zürbes, Petra; Drassner, Christina; Daniel, Christoph; Klewer, Monika; Steinkasserer, Alexander

    2015-11-01

    Mature dendritic cells (mDCs) are known as the most potent antigen-presenting cells (APCs) since they are also able to prime/induce naive T cells. Thus, mDCs play a pivotal role during the induction of antiviral immune responses. Remarkably, the cell surface molecule CD83, which was shown to have costimulatory properties, is targeted by herpes simplex virus 1 (HSV-1) for viral immune escape. Infection of mDCs with HSV-1 results in downmodulation of CD83, resulting in reduced T cell stimulation. In this study, we report that not only infected mDCs but also uninfected bystander cells in an infected culture show a significant CD83 reduction. We demonstrate that this effect is independent of phagocytosis and transmissible from infected to uninfected mDCs. The presence of specific viral proteins found in these uninfected bystander cells led to the hypothesis that viral proteins are transferred from infected to uninfected cells via L particles. These L particles are generated during lytic replication in parallel with full virions, called H particles. L particles contain viral proteins but lack the viral capsid and DNA. Therefore, these particles are not infectious but are able to transfer several viral proteins. Incubation of mDCs with L particles indeed reduced CD83 expression on uninfected bystander DCs, providing for the first time evidence that functional viral proteins are transmitted via L particles from infected mDCs to uninfected bystander cells, thereby inducing CD83 downmodulation. HSV-1 has evolved a number of strategies to evade the host's immune system. Among others, HSV-1 infection of mDCs results in an inhibited T cell activation caused by degradation of CD83. Interestingly, CD83 is lost not only from HSV-1-infected mDCs but also from uninfected bystander cells. The release of so-called L particles, which contain several viral proteins but lack capsid and DNA, during infection is a common phenomenon observed among several viruses, such as human

  16. Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies.

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    Susanne Eriksson

    2013-02-01

    Full Text Available HIV-1 reservoirs preclude virus eradication in patients receiving highly active antiretroviral therapy (HAART. The best characterized reservoir is a small, difficult-to-quantify pool of resting memory CD4(+ T cells carrying latent but replication-competent viral genomes. Because strategies targeting this latent reservoir are now being tested in clinical trials, well-validated high-throughput assays that quantify this reservoir are urgently needed. Here we compare eleven different approaches for quantitating persistent HIV-1 in 30 patients on HAART, using the original viral outgrowth assay for resting CD4(+ T cells carrying inducible, replication-competent viral genomes as a standard for comparison. PCR-based assays for cells containing HIV-1 DNA gave infected cell frequencies at least 2 logs higher than the viral outgrowth assay, even in subjects who started HAART during acute/early infection. This difference may reflect defective viral genomes. The ratio of infected cell frequencies determined by viral outgrowth and PCR-based assays varied dramatically between patients. Although strong correlations with the viral outgrowth assay could not be formally excluded for most assays, correlations achieved statistical significance only for integrated HIV-1 DNA in peripheral blood mononuclear cells and HIV-1 RNA/DNA ratio in rectal CD4(+ T cells. Residual viremia was below the limit of detection in many subjects and did not correlate with the viral outgrowth assays. The dramatic differences in infected cell frequencies and the lack of a precise correlation between culture and PCR-based assays raise the possibility that the successful clearance of latently infected cells may be masked by a larger and variable pool of cells with defective proviruses. These defective proviruses are detected by PCR but may not be affected by reactivation strategies and may not require eradication to accomplish an effective cure. A molecular understanding of the discrepancy

  17. Interferon-Lambda: A Potent Regulator of Intestinal Viral Infections.

    Science.gov (United States)

    Lee, Sanghyun; Baldridge, Megan T

    2017-01-01

    Interferon-lambda (IFN-λ) is a recently described cytokine found to be of critical importance in innate immune regulation of intestinal viruses. Endogenous IFN-λ has potent antiviral effects and has been shown to control multiple intestinal viruses and may represent a factor that contributes to human variability in response to infection. Importantly, recombinant IFN-λ has therapeutic potential against enteric viral infections, many of which lack other effective treatments. In this mini-review, we describe recent advances regarding IFN-λ-mediated regulation of enteric viruses with important clinical relevance including rotavirus, reovirus, and norovirus. We also briefly discuss IFN-λ interactions with other cytokines important in the intestine, and how IFN-λ may play a role in regulation of intestinal viruses by the commensal microbiome. Finally, we indicate currently outstanding questions regarding IFN-λ control of enteric infections that remain to be explored to enhance our understanding of this important immune molecule.

  18. Viral infection model with periodic lytic immune response

    International Nuclear Information System (INIS)

    Wang Kaifa; Wang Wendi; Liu Xianning

    2006-01-01

    Dynamical behavior and bifurcation structure of a viral infection model are studied under the assumption that the lytic immune response is periodic in time. The infection-free equilibrium is globally asymptotically stable when the basic reproductive ratio of virus is less than or equal to one. There is a non-constant periodic solution if the basic reproductive ratio of the virus is greater than one. It is found that period doubling bifurcations occur as the amplitude of lytic component is increased. For intermediate birth rates, the period triplication occurs and then period doubling cascades proceed gradually toward chaotic cycles. For large birth rate, the period doubling cascade proceeds gradually toward chaotic cycles without the period triplication, and the inverse period doubling can be observed. These results can be used to explain the oscillation behaviors of virus population, which was observed in chronic HBV or HCV carriers

  19. Peripheral viral infection induced microglial sensome genes and enhanced microglial cell activity in the hippocampus of neonatal piglets

    NARCIS (Netherlands)

    Ji, Peng; Schachtschneider, Kyle M.; Schook, Lawrence B.; Walker, Frederick R.; Johnson, Rodney W.

    2016-01-01

    Although poorly understood, early-life infection is predicted to affect brain microglial cells, making them hypersensitive to subsequent stimuli. To investigate this, we assessed gene expression in hippocampal tissue obtained from a previously published study reporting increased microglial cell

  20. Quantitative proteomic analysis of HIV-1 infected CD4+ T cells reveals an early host response in important biological pathways: Protein synthesis, cell proliferation, and T-cell activation

    Energy Technology Data Exchange (ETDEWEB)

    Navare, Arti T.; Sova, Pavel; Purdy, David E.; Weiss, Jeffrey M. [Department of Microbiology, University of Washington, Seattle, WA (United States); Wolf-Yadlin, Alejandro [Department of Genome Sciences, University of Washington, Seattle, WA (United States); Korth, Marcus J.; Chang, Stewart T.; Proll, Sean C. [Department of Microbiology, University of Washington, Seattle, WA (United States); Jahan, Tahmina A. [Proteomics Resource, UW Medicine at South Lake Union, Seattle, WA (United States); Krasnoselsky, Alexei L.; Palermo, Robert E. [Department of Microbiology, University of Washington, Seattle, WA (United States); Katze, Michael G., E-mail: honey@uw.edu [Department of Microbiology, University of Washington, Seattle, WA (United States); Washington National Primate Research Center, University of Washington, Seattle, WA (United States)

    2012-07-20

    Human immunodeficiency virus (HIV-1) depends upon host-encoded proteins to facilitate its replication while at the same time inhibiting critical components of innate and/or intrinsic immune response pathways. To characterize the host cell response on protein levels in CD4+ lymphoblastoid SUP-T1 cells after infection with HIV-1 strain LAI, we used mass spectrometry (MS)-based global quantitation with iTRAQ (isobaric tag for relative and absolute quantification). We found 266, 60 and 22 proteins differentially expressed (DE) (P-value{<=}0.05) at 4, 8, and 20 hours post-infection (hpi), respectively, compared to time-matched mock-infected samples. The majority of changes in protein abundance occurred at an early stage of infection well before the de novo production of viral proteins. Functional analyses of these DE proteins showed enrichment in several biological pathways including protein synthesis, cell proliferation, and T-cell activation. Importantly, these early changes before the time of robust viral production have not been described before.

  1. Dried blood spot HIV-1 RNA quantification: A useful tool for viral load monitoring among HIV-infected individuals in India

    Science.gov (United States)

    Neogi, Ujjwal; Gupta, Soham; Rodridges, Rashmi; Sahoo, Pravat Nalini; Rao, Shwetha D.; Rewari, Bharat B.; Shastri, Suresh; De Costa, Ayesha; Shet, Anita

    2012-01-01

    Background & objectives: Monitoring of HIV-infected individuals on antiretroviral treatment (ART) ideally requires periodic viral load measurements to ascertain adequate response to treatment. While plasma viral load monitoring is widely available in high-income settings, it is rarely used in resource-limited regions because of high cost and need for sophisticated sample transport. Dried blood spot (DBS) as source specimens for viral load measurement has shown promise as an alternative to plasma specimens and is likely to be a useful tool for Indian settings. The present study was undertaken to investigate the performance of DBS in HIV-1 RNA quantification against the standard plasma viral load assay. Methods: Between April-June 2011, 130 samples were collected from HIV-1-infected (n=125) and non-infected (n=5) individuals in two district clinics in southern India. HIV-1 RNA quantification was performed from DBS and plasma using Abbott m2000rt system after manual RNA extraction. Statistical analysis included correlation, regression and Bland-Altman analysis. Results: The sensitivity of DBS viral load was 97 per cent with viral loads >3.0 log10 copies/ml. Measurable viral load (>3.0 log 10 copies/ml) results obtained for the 74 paired plasma-DBS samples showed positive correlation between both the assays (r=0.96). For clinically acceptable viral load threshold values of >5,000 copies/ml, Bland-Altman plots showed acceptable limits of agreement (−0.21 to +0.8 log10 copies/ml). The mean difference was 0.29 log10 copies/ml. The cost of DBS was $2.67 lower compared to conventional plasma viral load measurement in the setting Interpretation & conclusions: The significant positive correlation with standard plasma-based assay and lower cost of DBS viral load monitoring suggest that DBS sampling can be a feasible and economical means of viral load monitoring in HIV-infected individual in India and in other resource-limited settings globally. PMID:23391790

  2. Early life exposure to antibiotics and the subsequent development of eczema, wheeze, and allergic sensitization in the first 2 years of life: the KOALA Birth Cohort Study

    NARCIS (Netherlands)

    Kummeling, Ischa; Stelma, Foekje F.; Dagnelie, Pieter C.; Snijders, Bianca E. P.; Penders, John; Huber, Machteld; van Ree, Ronald; van den Brandt, Piet A.

    2007-01-01

    OBJECTIVES: Antibiotic exposure in early life may be associated with atopic disease development either by interfering with bacterial commensal flora or by modifying the course of bacterial infections. We evaluated early life exposure to antibiotics and the subsequent development of eczema, wheeze,

  3. Dengue virus life cycle : viral and host factors modulating infectivity

    NARCIS (Netherlands)

    Rodenhuis-Zybert, Izabela A.; Wilschut, Jan; Smit, Jolanda M.

    Dengue virus (DENV 1-4) represents a major emerging arthropod-borne pathogen. All four DENV serotypes are prevalent in the (sub) tropical regions of the world and infect 50-100 million individuals annually. Whereas the majority of DENV infections proceed asymptomatically or result in self-limited

  4. Viral Meningitis

    Science.gov (United States)

    ... better from treatment such as an antiviral medicine. Antibiotics do not help viral infections, so they are not useful in the treatment of viral meningitis. However, antibiotics do fight bacteria, so they are very important ...

  5. Respiratory viral infections in infants with clinically suspected pertussis

    Directory of Open Access Journals (Sweden)

    Angela E. Ferronato

    2013-11-01

    Full Text Available Objective: to evaluate the frequency of respiratory viral infections in hospitalized infants with clinical suspicion of pertussis, and to analyze their characteristics at hospital admission and clinical outcomes. Methods: a historical cohort study was performed in a reference service for pertussis, in which the research of respiratory viruses was also a routine for infants hospitalized with respiratory problems. All infants reported as suspected cases of pertussis were included. Tests for Bordetella pertussis (BP (polymerase chain reaction/culture and for respiratory viruses (RVs (immunofluorescence were performed. Patients who received macrolides before hospitalization were excluded. Clinical data were obtained from medical records. Results: Among the 67 patients studied, BP tests were positive in 44%, and 26% were positive for RV. There was no etiological identification in 35%, and RV combined with BP was identified in 5%. All patients had similar demographic characteristics. Cough followed by inspiratory stridor or cyanosis was a strong predictor of pertussis, as well as prominent leukocytosis and lymphocytosis. Rhinorrhea and dyspnea were more frequent in viral infections. Macrolides were discontinued in 40% of patients who tested positive for RV and negative for BP. Conclusion: the results suggest that viral infection can be present in hospitalized infants with clinical suspicion of pertussis, and etiological tests may enable a reduction in the use of macrolides in some cases. However, the etiological diagnosis of respiratory virus infection, by itself, does not exclude the possibility of infection with BP. Resumo: Objetivo: avaliar a frequência das infecções por vírus respiratórios em lactentes hospitalizados com suspeita clínica de coqueluche e analisar suas características admissionais e evolutivas. Métodos: foi realizado um estudo de coorte histórica, em um serviço sentinela para coqueluche, no qual a pesquisa de v

  6. Early Life Exposures and Cancer

    Science.gov (United States)

    Early-life events and exposures have important consequences for cancer development later in life, however, epidemiological studies of early-life factors and cancer development later in life have had significant methodological challenges.

  7. TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection.

    Directory of Open Access Journals (Sweden)

    Saumya Maru

    2017-04-01

    Full Text Available Establishing functional tissue-resident memory (TRM cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells. Using this strategy, we found that antigen stimulation strength was inversely associated with the function of memory CD8 T cells during a persistent viral infection. We further show that CD8 TRM cells recruited to the brain following systemic infection with viruses expressing epitopes with suboptimal stimulation strength respond more efficiently to challenge CNS infection with virus expressing cognate antigen. These data demonstrate that the strength of antigenic stimulation during recruitment of CD8 T cells influences the functional integrity of TRM cells in a persistent viral infection.

  8. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

    Directory of Open Access Journals (Sweden)

    Jennifer H Campbell

    2014-12-01

    Full Text Available Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab once a week for three weeks beginning on 28 days post-infection (late. Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS, and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+ in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  9. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

    Science.gov (United States)

    Campbell, Jennifer H; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J; Tse, Samantha; Miller, Andrew D; González, R Gilberto; Salemi, Marco; Burdo, Tricia H; Williams, Kenneth C

    2014-12-01

    Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  10. Early events in the pathogenesis of foot-and-mouth disease in pigs; identification of oropharyngeal tonsils as sites of primary and sustained viral replication.

    Directory of Open Access Journals (Sweden)

    Carolina Stenfeldt

    Full Text Available A time-course study was performed to elucidate the early events of foot-and-mouth disease virus (FMDV infection in pigs subsequent to simulated natural, intra-oropharyngeal, inoculation. The earliest detectable event was primary infection in the lingual and paraepiglottic tonsils at 6 hours post inoculation (hpi characterized by regional localization of viral RNA, viral antigen, and infectious virus. At this time FMDV antigen was localized in cytokeratin-positive epithelial cells and CD172a-expressing leukocytes of the crypt epithelium of the paraepiglottic tonsils. De novo replication of FMDV was first detected in oropharyngeal swab samples at 12 hpi and viremia occurred at 18-24 hpi, approximately 24 hours prior to the appearance of vesicular lesions. From 12 through 78 hpi, microscopic detection of FMDV was consistently localized to cytokeratin-positive cells within morphologically characteristic segments of oropharyngeal tonsil crypt epithelium. During this period, leukocyte populations expressing CD172a, SLA-DQ class II and/or CD8 were found in close proximity to infected epithelial cells, but with little or no co-localization with viral proteins. Similarly, M-cells expressing cytokeratin-18 did not co-localize with FMDV proteins. Intra-epithelial micro-vesicles composed of acantholytic epithelial cells expressing large amounts of structural and non-structural FMDV proteins were present within crypts of the tonsil of the soft palate during peak clinical infection. These findings inculpate the paraepiglottic tonsils as the primary site of FMDV infection in pigs exposed via the gastrointestinal tract. Furthermore, the continuing replication of FMDV in the oropharyngeal tonsils during viremia and peak clinical infection with no concurrent amplification of virus occurring in the lower respiratory tract indicates that these sites are the major source of shedding of FMDV from pigs.

  11. A child with acute encephalopathy associated with quadruple viral infection

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    Keiko eNakata

    2015-04-01

    Full Text Available infection does not always result in AE. The risk factors for developing infantile AE upon such infection remain to be determined. Here we report an infant with AE coinfected with human herpesvirus 6 (HHV-6 and three picornaviruses: coxsackievirus A6 (CVA6, enterovirus D68 (EV-D68, and human parechovirus (HPeV. EV-D68 was vertically transmitted to the infant from his mother. CVA6 and HPeV were likely transmitted to the infant at the nursery school. HHV-6 might have been re-activated in the patient. It remains undetermined which pathogen played the central role in the AE pathogenesis. However, active, simultaneous infection by four viruses likely evoke a cytokine storm, leading to the pathogenesis of AE. Conclusion: Infant cases with active quadruple infection by potentially AE-causing viruses have seldom been reported, partly because systematic nucleic acid-based laboratory tests on picornaviruses are not common. We propose that simultaneous viral infection may serve as a risk factor for the development of AE.

  12. TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice

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    Lee Adam Wheeler

    2016-05-01

    Full Text Available Despite their antiviral effect, the in vivo effect of interferons on HIV transmission is difficult to predict, because interferons also activate and recruit HIV-susceptible cells to sites of infection. HIV does not normally induce type I interferons in infected cells, but does if TREX1 is knocked down. Here, we investigated the effect of topical TREX1 knockdown and local interferon production on HIV transmission in human cervicovaginal explants and humanized mice. In explants in which TREX1 was knocked down, HIV induced interferons, which blocked infection. In humanized mice, even though TREX1 knockdown increased infiltrating immune cells, it delayed viral replication for 3–4 weeks. Similarly intravaginal application of type I interferons the day before HIV infection induced interferon responsive genes, reduced inflammation, and decreased viral replication. However, intravenous interferon enhanced inflammation and infection. Thus, in models of human sexual transmission, a localized interferon response inhibits HIV transmission but systemic interferons do not.

  13. Diagnosing viral and bacterial respiratory infections in acute COPD exacerbations by an electronic nose : a pilot study

    NARCIS (Netherlands)

    van Geffen, Wouter H; Bruins, Marcel; Kerstjens, Huib A M

    2016-01-01

    Respiratory infections, viral or bacterial, are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). A rapid, point-of-care, and easy-to-use tool distinguishing viral and bacterial from other causes would be valuable in routine clinical care. An electronic nose

  14. MicroRNAs in the host response to viral infections of veterinary importance

    Directory of Open Access Journals (Sweden)

    Mohamed Samir Ahmed

    2016-10-01

    Full Text Available The discovery of small regulatory non-coding RNAs has been an exciting advance in the field of genomics. MicroRNAs (miRNAs are endogenous RNA molecules, approximately 22 nucleotides in length that regulate gene expression, mostly at the post-transcriptional level. MiRNA profiling technologies have made it possible to identify and quantify novel miRNAs and to study their regulation and potential roles in disease pathogenesis. Although miRNAs have been extensively investigated in viral infections of humans, their implications in viral diseases affecting animals of veterinary importance are much less understood. The number of annotated miRNAs in different animal species is growing continuously, and novel roles in regulating host-pathogen interactions are being discovered, for instance miRNA-mediated augmentation of viral transcription and replication. In this review, we present an overview of synthesis and function of miRNAs and an update on the current state of research on host-encoded miRNAs in the genesis of viral infectious diseases in their natural animal host as well as in selected in vivo and in vitro laboratory models.

  15. Use of quantitative real-time RT-PCR to investigate the correlation between viremia and viral shedding of canine distemper virus, and infection outcomes in experimentally infected dogs.

    Science.gov (United States)

    Sehata, Go; Sato, Hiroaki; Ito, Toshihiro; Imaizumi, Yoshitaka; Noro, Taichi; Oishi, Eiji

    2015-07-01

    We used real-time RT-PCR and virus titration to examine canine distemper virus (CDV) kinetics in peripheral blood and rectal and nasal secretions from 12 experimentally infected dogs. Real-time RT-PCR proved extremely sensitive, and the correlation between the two methods for rectal and nasal (r=0.78, 0.80) samples on the peak day of viral RNA was good. Although the dogs showed diverse symptoms, viral RNA kinetics were similar; the peak of viral RNA in the symptomatic dogs was consistent with the onset of symptoms. These results indicate that real-time RT-PCR is sufficiently sensitive to monitor CDV replication in experimentally infected dogs regardless of the degree of clinical manifestation and suggest that the peak of viral RNA reflects active CDV replication.

  16. p53 and the Viral Connection: Back into the Future ‡

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    Ronit Aloni-Grinstein

    2018-06-01

    Full Text Available The discovery of the tumor suppressor p53, through its interactions with proteins of tumor-promoting viruses, paved the way to the understanding of p53 roles in tumor virology. Over the years, accumulating data suggest that WTp53 is involved in the viral life cycle of non-tumor-promoting viruses as well. These include the influenza virus, smallpox and vaccinia viruses, the Zika virus, West Nile virus, Japanese encephalitis virus, Human Immunodeficiency Virus Type 1, Human herpes simplex virus-1, and more. Viruses have learned to manipulate WTp53 through different strategies to improve their replication and spreading in a stage-specific, bidirectional way. While some viruses require active WTp53 for efficient viral replication, others require reduction/inhibition of WTp53 activity. A better understanding of WTp53 functionality in viral life may offer new future clinical approaches, based on WTp53 manipulation, for viral infections.

  17. Interleukin-27 is differentially associated with HIV viral load and CD4+ T cell counts in therapy-naive HIV-mono-infected and HIV/HCV-co-infected Chinese.

    Directory of Open Access Journals (Sweden)

    Lai He

    Full Text Available Human Immunodeficiency Virus (HIV infection and the resultant Acquired Immunodeficiency Syndrome (AIDS epidemic are major global health challenges; hepatitis C virus (HCV co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27, a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.

  18. Can the Pelargonium sidoides root extract EPs® 7630 prevent asthma attacks during viral infections of the upper respiratory tract in children?

    Science.gov (United States)

    Tahan, Fulya; Yaman, Melih

    2013-01-15

    Asthma is a chronic disease characterized by airway inflammation. Viral infection initiates an immune inflammatory response that may produce asthma attacks. There is no effective preventing therapy for asthma attack during upper respiratory tract viral infections. To investigate the efficacy of 5 days of Pelargonium sidoides therapy for preventing asthma attack during upper respiratory tract viral infections. Sixty one asthmatic children with upper respiratory tract viral infection were enrolled in the study. The patients were randomized to receive Pelargonium sidoides daily for 5 days (n=30) or not (n=31). Before and after treatment, they all were examined and symptom scores were determined. Following five days treatment, children were evaluated whether or not they had an asthma attack. Treatment with Pelargonium sidoides was not associated with a statistically significant differences in fever and muscle aches (p>0.05, Chi-square test). There were significant differences in cough frequency and nasal congestion between the groups (pasthma attack between the groups (pasthma attack. Our study shows that Pelargonium sidoides may prevent asthma attacks during upper respiratory tract viral infections. Copyright © 2012 Elsevier GmbH. All rights reserved.

  19. CRISPR-Cas type I-A Cascade complex couples viral infection surveillance to host transcriptional regulation in the dependence of Csa3b.

    Science.gov (United States)

    He, Fei; Vestergaard, Gisle; Peng, Wenfang; She, Qunxin; Peng, Xu

    2017-02-28

    CRISPR-Cas (clustered regularly interspaced short palindromic repeats and the associated genes) constitute adaptive immune systems in bacteria and archaea and they provide sequence specific immunity against foreign nucleic acids. CRISPR-Cas systems are activated by viral infection. However, little is known about how CRISPR-Cas systems are activated in response to viral infection or how their expression is controlled in the absence of viral infection. Here, we demonstrate that both the transcriptional regulator Csa3b, and the type I-A interference complex Cascade, are required to transcriptionally repress the interference gene cassette in the archaeon Sulfolobus. Csa3b binds to two palindromic repeat sites in the promoter region of the cassette and facilitates binding of the Cascade to the promoter region. Upon viral infection, loading of Cascade complexes onto crRNA-matching protospacers leads to relief of the transcriptional repression. Our data demonstrate a mechanism coupling CRISPR-Cas surveillance of protospacers to transcriptional regulation of the interference gene cassette thereby allowing a fast response to viral infection. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Small RNA Profiling in Dengue Virus 2-Infected Aedes Mosquito Cells Reveals Viral piRNAs and Novel Host miRNAs.

    Science.gov (United States)

    Miesen, Pascal; Ivens, Alasdair; Buck, Amy H; van Rij, Ronald P

    2016-02-01

    In Aedes mosquitoes, infections with arthropod-borne viruses (arboviruses) trigger or modulate the expression of various classes of viral and host-derived small RNAs, including small interfering RNAs (siRNAs), PIWI interacting RNAs (piRNAs), and microRNAs (miRNAs). Viral siRNAs are at the core of the antiviral RNA interference machinery, one of the key pathways that limit virus replication in invertebrates. Besides siRNAs, Aedes mosquitoes and cells derived from these insects produce arbovirus-derived piRNAs, the best studied examples being viruses from the Togaviridae or Bunyaviridae families. Host miRNAs modulate the expression of a large number of genes and their levels may change in response to viral infections. In addition, some viruses, mostly with a DNA genome, express their own miRNAs to regulate host and viral gene expression. Here, we perform a comprehensive analysis of both viral and host-derived small RNAs in Aedes aegypti Aag2 cells infected with dengue virus 2 (DENV), a member of the Flaviviridae family. Aag2 cells are competent in producing all three types of small RNAs and provide a powerful tool to explore the crosstalk between arboviral infection and the distinct RNA silencing pathways. Interestingly, besides the well-characterized DENV-derived siRNAs, a specific population of viral piRNAs was identified in infected Aag2 cells. Knockdown of Piwi5, Ago3 and, to a lesser extent, Piwi6 results in reduction of vpiRNA levels, providing the first genetic evidence that Aedes PIWI proteins produce DENV-derived small RNAs. In contrast, we do not find convincing evidence for the production of virus-derived miRNAs. Neither do we find that host miRNA expression is strongly changed upon DENV2 infection. Finally, our deep-sequencing analyses detect 30 novel Aedes miRNAs, complementing the repertoire of regulatory small RNAs in this important vector species.

  1. Acute respiratory viral infections in pediatric cancer patients undergoing chemotherapy

    Directory of Open Access Journals (Sweden)

    Eliana C.A. Benites

    2014-07-01

    Full Text Available OBJECTIVE: to estimate the prevalence of infection by respiratory viruses in pediatric patients with cancer and acute respiratory infection (ARI and/or fever. METHODS: cross-sectional study, from January 2011 to December 2012. The secretions of nasopharyngeal aspirates were analyzed in children younger than 21 years with acute respiratory infections. Patients were treated at the Grupo em Defesa da Criança Com Câncer (Grendacc and University Hospital (HU, Jundiaí, SP. The rapid test was used for detection of influenza virus (Kit Biotrin, Inc. Ireland, and real-time multiplex polymerase chain reaction (FTD, Respiratory pathogens, multiplex Fast Trade Kit, Malta for detection of influenza virus (H1N1, B, rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus, human parechovirus, bocavirus, metapneumovirus, and human coronavirus. The prevalence of viral infection was estimated and association tests were used (χ2 or Fisher's exact test. RESULTS: 104 samples of nasopharyngeal aspirate and blood were analyzed. The median age was 12 ± 5.2 years, 51% males, 68% whites, 32% had repeated ARIs, 32% prior antibiotic use, 19.8% cough, and 8% contact with ARIs. A total of 94.3% were in good general status. Acute lymphocytic leukemia (42.3% was the most prevalent neoplasia. Respiratory viruses were detected in 50 samples: rhinoviruses (23.1%, respiratory syncytial virus AB (8.7%, and coronavirus (6.8%. Co-detection occurred in 19% of cases with 2 viruses and in 3% of those with 3 viruses, and was more frequent between rhinovirus and coronavirus 43. Fever in neutropenic patients was observed in 13%, of which four (30.7 were positive for viruses. There were no deaths. CONCLUSIONS: the prevalence of respiratory viruses was relevant in the infectious episode, with no increase in morbidity and mortality. Viral co-detection was frequent in patients with cancer and ARIs.

  2. Tip60 degradation by adenovirus relieves transcriptional repression of viral transcriptional activator EIA.

    Science.gov (United States)

    Gupta, A; Jha, S; Engel, D A; Ornelles, D A; Dutta, A

    2013-10-17

    Adenoviruses are linear double-stranded DNA viruses that infect human and rodent cell lines, occasionally transform them and cause tumors in animal models. The host cell challenges the virus in multifaceted ways to restrain viral gene expression and DNA replication, and sometimes even eliminates the infected cells by programmed cell death. To combat these challenges, adenoviruses abrogate the cellular DNA damage response pathway. Tip60 is a lysine acetyltransferase that acetylates histones and other proteins to regulate gene expression, DNA damage response, apoptosis and cell cycle regulation. Tip60 is a bona fide tumor suppressor as mice that are haploid for Tip60 are predisposed to tumors. We have discovered that Tip60 is degraded by adenovirus oncoproteins EIB55K and E4orf6 by a proteasome-mediated pathway. Tip60 binds to the immediate early adenovirus promoter and suppresses adenovirus EIA gene expression, which is a master regulator of adenovirus transcription, at least partly through retention of the virally encoded repressor pVII on this promoter. Thus, degradation of Tip60 by the adenoviral early proteins is important for efficient viral early gene transcription and for changes in expression of cellular genes.

  3. Early infection and prognosis after acute stroke

    DEFF Research Database (Denmark)

    Kammersgaard, L P; Jørgensen, H S; Reith, J

    2001-01-01

    Infection is a frequent complication in the early course of acute stroke and may adversely affect stroke outcome. In the present study, we investigate early infection developing in patients within 3 days of admission to the hospital and its independent relation to recovery and stroke outcome....... In addition, we identify predictors for early infections, infection subtypes, and their relation to initial stroke severity....

  4. Hepatitis A virus cellular receptor 2 (HAVCR2) is decreased with viral infection and regulates pro-labour mediators OA.

    Science.gov (United States)

    Liong, Stella; Lim, Ratana; Barker, Gillian; Lappas, Martha

    2017-07-01

    Intrauterine infection caused by viral infection has been implicated to contribute to preterm birth. Hepatitis A virus cellular receptor 2 (HAVCR2) regulates inflammation in non-gestational tissues in response to viral infection. The aims of this study were to determine the effect of: (i) viral dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) on HAVCR2 expression; and (ii) HAVCR2 silencing by siRNA (siHAVCR2) in primary amnion and myometrial cells on poly(I:C)-induced inflammation. In human foetal membranes and myometrium, HAVCR2 mRNA and protein expression was decreased when exposed to poly(I:C). Treatment of primary amnion and myometrial cells with poly(I:C) significantly increased the expression and release of pro-inflammatory cytokines TNF, IL1A, IL1B and IL6; the expression of chemokines CXCL8 and CCL2; the expression and secretion of adhesion molecules ICAM1 and VCAM1; and PTGS2 and PTGFR mRNA expression and the release of prostaglandin PGF 2α . This increase was significantly augmented in cells transfected with siHAVCR2. Furthermore, mRNA expression of anti-inflammatory cytokines IL4 and IL10 was significantly decreased. Collectively, our data suggest that HAVCR2 regulates cytokines, chemokines, prostaglandins and cell adhesion molecules in the presence of viral infection. This suggests a potential for HAVCR2 activators as therapeutics for the management of preterm birth associated with viral infections. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Latency of Epstein-Barr virus is stabilized by antisense-mediated control of the viral immediate-early gene BZLF-1.

    Science.gov (United States)

    Prang, N; Wolf, H; Schwarzmann, F

    1999-12-01

    The ability of the Epstein-Barr virus (EBV) to avoid lytic replication and to establish a latent infection in B-lymphocytes is fundamental for its lifelong persistence and the pathogenesis of various EBV-associated diseases. The viral immediate-early gene BZLF-1 plays a key role for the induction of lytic replication and its activity is strictly regulated on different levels of gene expression. Recently, it was demonstrated that BZLF-1 is also controlled by a posttranscriptional mechanism. Transient synthesis of a mutated competitor RNA saturated this mechanism and caused both expression of the BZLF-1 protein and the induction of lytic viral replication. Using short overlapping fragments of the competitor, it is shown that this control acts on the unspliced primary transcript. RT-PCR demonstrated unspliced BZLF-1 RNA in latently infected B-lymphocytes in the absence of BZLF-1 protein. Due to the complementarity of the gene BZLF-1 and the latency-associated gene EBNA-1 on the opposite strand of the genome, we propose an antisense-mediated mechanism. RNase protection assays demonstrated transcripts in antisense orientation to the BZLF-1 transcript during latency, which comprise a comparable constellation to other herpesviruses. A combined RNAse protection/RT-PCR assay detected the double-stranded hybrid RNA, consisting of the unspliced BZLF-1 transcript and a noncoding intron of the EBNA-1 gene. Binding of BZLF-1 transcripts is suggested to be an important backup control mechanism in addition to transcriptional regulation, stabilizing latency and preventing inappropriate lytic viral replication in vivo. Copyright 1999 Wiley-Liss, Inc.

  6. Treatment of primary HIV infection

    NARCIS (Netherlands)

    Grijsen, M.L.

    2013-01-01

    In this thesis we studied the treatment of PHI. Early cART transiently lowered the viral setpoint and deferred the need for restart of cART during chronic HIV infection, which was most likely caused by the effects of the CD4 gain during treatment and the transient lowering of the viral setpoint.

  7. Association of early-life antibiotic use and protective effects of breastfeeding

    NARCIS (Netherlands)

    Korpela, Katri; Salonen, Anne; Virta, Lauri J.; Kekkonen, Riina A.; Vos, de Willem M.

    2016-01-01

    Importance: Long duration of breastfeeding is known to reduce the frequency of infections and the risk of overweight, both of which are prevalent health problems among children, but the mechanisms are unclear. Objectives: To test whether early-life antibiotic use in children prevents the

  8. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

    Directory of Open Access Journals (Sweden)

    Abderaouf Damouche

    2015-09-01

    Full Text Available Two of the crucial aspects of human immunodeficiency virus (HIV infection are (i viral persistence in reservoirs (precluding viral eradication and (ii chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART-controlled HIV-infected patients. The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF; the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV. The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART. Data on the impact of HIV on the SVF (especially in individuals not receiving ART are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low

  9. Susceptibility to viral infection is enhanced by stable expression of 3A or 3AB proteins from foot-and-mouth disease virus

    International Nuclear Information System (INIS)

    Rosas, Maria F.; Vieira, Yuri A.; Postigo, Raul; Martin-Acebes, Miguel A.; Armas-Portela, Rosario; Martinez-Salas, Encarnacion; Sobrino, Francisco

    2008-01-01

    The foot-and-mouth disease virus (FMDV) 3A protein is involved in virulence and host range. A distinguishing feature of FMDV 3B among picornaviruses is that three non-identical copies are encoded in the viral RNA and required for optimal replication in cell culture. Here, we have studied the involvement of the 3AB region on viral infection using constitutive and transient expression systems. BHK-21 stably transformed clones expressed low levels of FMDV 3A or 3A(B) proteins in the cell cytoplasm. Transformed cells stably expressing these proteins did not exhibit inner cellular rearrangements detectable by electron microscope analysis. Upon FMDV infection, clones expressing either 3A alone or 3A(B) proteins showed a significant increase in the percentage of infected cells, the number of plaque forming units and the virus yield. The 3A-enhancing effect was specific for FMDV as no increase in viral multiplication was observed in transformed clones infected with another picornavirus, encephalomyocarditis virus, or the negative-strand RNA virus vesicular stomatitis virus. A potential role of 3A protein in viral RNA translation was discarded by the lack of effect on FMDV IRES-dependent translation. Increased viral susceptibility was not caused by a released factor; neither the supernatant of transformed clones nor the addition of purified 3A protein to the infection medium was responsible for this effect. Unlike stable expression, high levels of 3A or 3A(B) protein transient expression led to unspecific inhibition of viral infection. Therefore, the effect observed on viral yield, which inversely correlated with the intracellular levels of 3A protein, suggests a transacting role operating on the FMDV multiplication cycle

  10. Larger Subcortical Gray Matter Structures and Smaller Corpora Callosa at Age 5 Years in HIV Infected Children on Early ART

    Directory of Open Access Journals (Sweden)

    Steven R. Randall

    2017-11-01

    Full Text Available Sub-Saharan Africa is home to 90% of HIV infected (HIV+ children. Since the advent of antiretroviral therapy (ART, HIV/AIDS has transitioned to a chronic condition where central nervous system (CNS damage may be ongoing. Although, most guidelines recommend early ART to reduce CNS viral reservoirs, the brain may be more vulnerable to potential neurotoxic effects of ART during the rapid development phase in the first years of life. Here we investigate differences in subcortical volumes between 5-year-old HIV+ children who received early ART (before age 18 months and uninfected children using manual tracing of Magnetic Resonance Images. Participants included 61 Xhosa children (43 HIV+/18 uninfected, mean age = 5.4 ± 0.3 years, 25 male from the children with HIV early antiretroviral (CHER trial; 27 children initiated ART before 12 weeks of age (ART-Before12Wks and 16 after 12 weeks (ART-After12Wks. Structural images were acquired on a 3T Allegra MRI in Cape Town and manually traced using MultiTracer. Volumetric group differences (HIV+ vs. uninfected; ART-Before12Wks vs. ART-After12Wks were examined for the caudate, nucleus accumbens (NA, putamen (Pu, globus pallidus (GP, and corpus callosum (CC, as well as associations within infected children of structure volumes with age at ART initiation and CD4/CD8 as a proxy for immune health. HIV+ children had significantly larger NA and Pu volumes bilaterally and left GP volumes than controls, whilst CC was smaller. Bilateral Pu was larger in both treatment groups compared to controls, while left GP and bilateral NA were enlarged only in ART-After12Wks children. CC was smaller in both treatment groups compared to controls, and smaller in ART-After12Wks compared to ART-Before12Wks. Within infected children, delayed ART initiation was associated with larger Pu volumes, effects that remained significant when controlling for sex and duration of treatment interruption (left β = 0.447, p = 0.005; right β = 0

  11. Evasion of Early Antiviral Responses by Herpes Simplex Viruses

    Science.gov (United States)

    Suazo, Paula A.; Ibañez, Francisco J.; Retamal-Díaz, Angello R.; Paz-Fiblas, Marysol V.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.

    2015-01-01

    Besides overcoming physical constraints, such as extreme temperatures, reduced humidity, elevated pressure, and natural predators, human pathogens further need to overcome an arsenal of antimicrobial components evolved by the host to limit infection, replication and optimally, reinfection. Herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) infect humans at a high frequency and persist within the host for life by establishing latency in neurons. To gain access to these cells, herpes simplex viruses (HSVs) must replicate and block immediate host antiviral responses elicited by epithelial cells and innate immune components early after infection. During these processes, infected and noninfected neighboring cells, as well as tissue-resident and patrolling immune cells, will sense viral components and cell-associated danger signals and secrete soluble mediators. While type-I interferons aim at limiting virus spread, cytokines and chemokines will modulate resident and incoming immune cells. In this paper, we discuss recent findings relative to the early steps taking place during HSV infection and replication. Further, we discuss how HSVs evade detection by host cells and the molecular mechanisms evolved by these viruses to circumvent early antiviral mechanisms, ultimately leading to neuron infection and the establishment of latency. PMID:25918478

  12. Dopamine and serotonin levels following prenatal viral infection in mouse--implications for psychiatric disorders such as schizophrenia and autism.

    Science.gov (United States)

    Winter, Christine; Reutiman, Teri J; Folsom, Timothy D; Sohr, Reinhard; Wolf, Rainer J; Juckel, Georg; Fatemi, S Hossein

    2008-10-01

    Prenatal viral infection has been associated with neurodevelopmental disorders such as schizophrenia and autism. It has previously been demonstrated that viral infection causes deleterious effects on brain structure and function in mouse offspring following late first trimester (E9) and middle-late second trimester (E18) administration of influenza virus. Neurochemical analysis following infection on E18 using this model has revealed significantly altered levels of serotonin, 5-hydroxyindoleacetic acid, and taurine, but not dopamine. In order to monitor these different patterns of monoamine expression in exposed offspring in more detail and to see if there are changes in the dopamine system at another time point, pregnant C57BL6J mice were infected with a sublethal dose of human influenza virus or sham-infected using vehicle solution on E16. Male offspring of the infected mice were collected at P0, P14, and P56, their brains removed and cerebellum dissected and flash frozen. Dopamine and serotonin levels were then measured using HPLC-ED technique. When compared to controls, there was a significant decrease in serotonin levels in the cerebella of offspring of virally exposed mice at P14. No differences in levels of dopamine were observed in exposed and control mice, although there was a significant decrease in dopamine at P14 and P56 when compared to P0. The present study shows that the serotonergic system is disrupted following prenatal viral infection, potentially modelling disruptions that occur in patients with schizophrenia and autism.

  13. The landscape of viral proteomics and its potential to impact human health

    Energy Technology Data Exchange (ETDEWEB)

    Oxford, Kristie L.; Wendler, Jason P.; McDermott, Jason E.; White III, Richard A.; Powell, Joshua D.; Jacobs, Jon M.; Adkins, Joshua N.; Waters, Katrina M.

    2016-05-06

    Translating the intimate discourse between viruses and their host cells during infection is a challenging but critical task for development of antiviral interventions and diagnostics. Viruses commandeer cellular processes at every step of their life cycle, altering expression of genes and proteins. Advances in mass spectrometry-based proteomic technologies are enhancing studies of viral pathogenesis by identifying virus-induced changes in the protein repertoire of infected cells or extracellular fluids. Interpretation of proteomics results using knowledge of cellular pathways and networks leads to identification of proteins that influence a range of infection processes, thereby focusing efforts for clinical diagnoses and therapeutics development. Herein we discuss applications of global proteomic studies of viral infections with the goal of providing a basis for improved studies that will benefit community-wide data integration and interpretation.

  14. Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections.

    Science.gov (United States)

    Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

    2015-01-01

    Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1-4), rhinovirus, adenovirus (A-F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011-2013. The results were corroborated in an independent cohort collected in the UK. A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12-24 months age group. The most frequently observed co-infection patterns were RSV-Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV-bocavirus / bocavirus-influenza (5 patients, 5.2%, UK cohort). The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12-24 months of age. The clinical significance of these findings is unclear but should warrant further analysis.

  15. Viral etiology and clinical profiles of children with severe acute respiratory infections in China.

    Directory of Open Access Journals (Sweden)

    Chen Zhang

    Full Text Available No comprehensive analysis is available on the viral etiology and clinical characterization among children with severe acute respiratory infection (SARI in China during 2009 H1N1 pandemic and post-pandemic period.Cohort of 370 hospitalized children (1 to 72 months with SARI from May 2008 to March 2010 was enrolled in this study. Nasopharyngeal aspirate (NPA specimens were tested by a commercial assay for 18 respiratory viral targets. The viral distribution and its association with clinical character were statistically analyzed.Viral pathogen was detected in 350 (94.29% of children with SARI. Overall, the most popular viruses were: enterovirus/rhinovirus (EV/RV (54.05%, respiratory syncytial virus (RSV (51.08%, human bocavirus (BoCA (33.78%, human parainfluenzaviruse type 3 (PIV3 (15.41%, and adenovirus (ADV (12.97%. Pandemic H1N1 was the dominant influenza virus (IFV but was only detected in 20 (5.41% of children. Moreover, detection rate of RSV and human metapneumovirus (hMPV among suburb participants were significantly higher than that of urban area (P<0.05. Incidence of VSARI among suburb participants was also significant higher, especially among those of 24 to 59 months group (P<0.05.Piconaviruses (EV/RV and paramyxoviruses are the most popular viral pathogens among children with SARI in this study. RSV and hMPV significantly increase the risk of SARI, especially in children younger than 24 months. Higher incidence of VSARI and more susceptibilities to RSV and hMPV infections were found in suburban patients.

  16. Dynamic and nucleolin-dependent localization of human cytomegalovirus UL84 to the periphery of viral replication compartments and nucleoli.

    Science.gov (United States)

    Bender, Brian J; Coen, Donald M; Strang, Blair L

    2014-10-01

    Protein-protein and protein-nucleic acid interactions within subcellular compartments are required for viral genome replication. To understand the localization of the human cytomegalovirus viral replication factor UL84 relative to other proteins involved in viral DNA synthesis and to replicating viral DNA in infected cells, we created a recombinant virus expressing a FLAG-tagged version of UL84 (UL84FLAG) and used this virus in immunofluorescence assays. UL84FLAG localization differed at early and late times of infection, transitioning from diffuse distribution throughout the nucleus to exclusion from the interior of replication compartments, with some concentration at the periphery of replication compartments with newly labeled DNA and the viral DNA polymerase subunit UL44. Early in infection, UL84FLAG colocalized with the viral single-stranded DNA binding protein UL57, but colocalization became less prominent as infection progressed. A portion of UL84FLAG also colocalized with the host nucleolar protein nucleolin at the peripheries of both replication compartments and nucleoli. Small interfering RNA (siRNA)-mediated knockdown of nucleolin resulted in a dramatic elimination of UL84FLAG from replication compartments and other parts of the nucleus and its accumulation in the cytoplasm. Reciprocal coimmunoprecipitation of viral proteins from infected cell lysates revealed association of UL84, UL44, and nucleolin. These results indicate that UL84 localization during infection is dynamic, which is likely relevant to its functions, and suggest that its nuclear and subnuclear localization is highly dependent on direct or indirect interactions with nucleolin. Importance: The protein-protein interactions among viral and cellular proteins required for replication of the human cytomegalovirus (HCMV) DNA genome are poorly understood. We sought to understand how an enigmatic HCMV protein critical for virus replication, UL84, localizes relative to other viral and cellular

  17. [Human enterovirus infection status and clinical characteristics of 274 patients with viral encephalitis in Henan Province, 2011-2012].

    Science.gov (United States)

    Ma, H X; Pan, J J; Li, Y; Kang, K; Huang, X Y; You, A G; Xu, B L

    2017-02-06

    Objective: To investigate human enterovirus (HEV) infection and clinical characteristics of viral encephalitis patients in Pingdingshan, Henan Province. Methods: Cerebrospinal fluid specimens and epidemiological information were collected from 274 viral encephalitis patients in the departments of pediatrics and neurology in hospitals in Pingdingshan, Henan Province, from April 2011 to August 2012. Patients with bacterial infections were excluded from the study. Demographic information was collected by questionnaires and clinical information was mainly obtained from hospital examinations. Viral RNA was extracted using magnetic bead extraction. Real-time RT-PCR was then performed for HEV, CV-A16, and EV-A71 testing. SPSS statistical software was statistical analyses. Significant differences were determined using the chi-squared test ( P15 years old age groups, HEV infections comprised 31.5% (53/168), 52.9% (18/34), 53.0% (35/66), and 16.7% (1/6) (χ(2)=13.10, P= 0.003), respectively. The EV-A71 infection rates were 17.9% (30/168), 23.5% (8/34), 6.1% (4/66), and 0 (χ(2)=8.04, P= 0.045), respectively. The other enterovirus (OEV) infection rates were 12.5% (21/168), 29.4% (10/34), 48.5% (32/66), and 16.7% (1/6) (χ(2)=35.19, P< 0.001), respectively. The rate of vomiting in OEV and EV-A71 infected patients was 73% (44/60) and 26% (11/42), respectively, while the frequency of skin rash in OEV and EV-A71 infected patients was 32% (19/60) and 79% (33/42), respectively. Approximately 95% (99/104) of patients infected with HEV had a fever, and the breathing rhythm change rate was 19% (20/104), which was lower than that of patients without HEV infection (36.8% (60/163)) (χ(2)=9.35, P= 0.002). Conclusion: In Pingdingshan, HEV was a major causative agent of viral encephalitis and the rate of OEV infection was high, especially in children aged 3-15 years old. Fever was a common clinical symptom of patients infected with HEV. Patients infected with OEV primarily exhibited

  18. Increasing P limitation and viral infection impact lipid remodeling of the picophytoplankter Micromonas pusilla

    Science.gov (United States)

    Maat, Douwe S.; Bale, Nicole J.; Hopmans, Ellen C.; Sinninghe Damsté, Jaap S.; Schouten, Stefan; Brussaard, Corina P. D.

    2016-03-01

    The intact polar lipid (IPL) composition of phytoplankton is plastic and dependent on environmental factors. Previous studies have shown that phytoplankton under low phosphorus (P) availability substitutes phosphatidylglycerols (PGs) with sulfoquinovosyldiacylglycerols (SQDGs) and digalactosyldiacylglycerols (DGDGs). However, these studies focused merely on P depletion, while phytoplankton in the natural environment often experience P limitation whereby the strength depends on the supply rate of the limiting nutrient. Here we report on the IPL composition of axenic cultures of the picophotoeukaryote Micromonas pusilla under different degrees of P limitation, i.e., P-controlled chemostats at 97 and 32 % of the maximum growth rate, and P starvation (obtained by stopping P supply to these chemostats). P-controlled cultures were also grown at elevated partial carbon dioxide pressure (pCO2) to mimic a future scenario of strengthened vertical stratification in combination with ocean acidification. Additionally, we tested the influence of viral infection for this readily infected phytoplankton host species. Results show that both SQDG : PG and DGDG : PG ratios increased with enhanced P limitation. Lipid composition was, however, not affected by enhanced (750 vs. 370 µatm) pCO2. In the P-starved virally infected cells the increase in SQDG : PG and DGDG : PG ratios was lower, whereby the extent depended on the growth rate of the host cultures before infection. The lipid membrane of the virus MpV-08T itself lacked some IPLs (e.g., monogalactosyldiacylglycerols; MGDGs) in comparison with its host. This study demonstrates that, besides P concentration, also the P supply rate, viral infection and even the history of the P supply rate can affect phytoplankton lipid composition (i.e., the non-phospholipid : phospholipid ratio), with possible consequences for the nutritional quality of phytoplankton.

  19. Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis.

    Science.gov (United States)

    Rossi, Matteo; Castiglioni, Patrik; Hartley, Mary-Anne; Eren, Remzi Onur; Prével, Florence; Desponds, Chantal; Utzschneider, Daniel T; Zehn, Dietmar; Cusi, Maria G; Kuhlmann, F Matthew; Beverley, Stephen M; Ronet, Catherine; Fasel, Nicolas

    2017-05-09

    The presence of the endogenous Leishmania RNA virus 1 (LRV1) replicating stably within some parasite species has been associated with the development of more severe forms of leishmaniasis and relapses after drug treatment in humans. Here, we show that the disease-exacerbatory role of LRV1 relies on type I IFN (type I IFNs) production by macrophages and signaling in vivo. Moreover, infecting mice with the LRV1-cured Leishmania guyanensis ( LgyLRV1 - ) strain of parasites followed by type I IFN treatment increased lesion size and parasite burden, quantitatively reproducing the LRV1-bearing ( LgyLRV1 + ) infection phenotype. This finding suggested the possibility that exogenous viral infections could likewise increase pathogenicity, which was tested by coinfecting mice with L. guyanensis and lymphocytic choriomeningitis virus (LCMV), or the sand fly-transmitted arbovirus Toscana virus (TOSV). The type I IFN antiviral response increased the pathology of L. guyanensis infection, accompanied by down-regulation of the IFN-γ receptor normally required for antileishmanial control. Further, LCMV coinfection of IFN-γ-deficient mice promoted parasite dissemination to secondary sites, reproducing the LgyLRV1 + metastatic phenotype. Remarkably, LCMV coinfection of mice that had healed from L. guyanensis infection induced reactivation of disease pathology, overriding the protective adaptive immune response. Our findings establish that type I IFN-dependent responses, arising from endogenous viral elements (dsRNA/LRV1), or exogenous coinfection with IFN-inducing viruses, are able to synergize with New World Leishmania parasites in both primary and relapse infections. Thus, viral infections likely represent a significant risk factor along with parasite and host factors, thereby contributing to the pathological spectrum of human leishmaniasis.

  20. Portrait of a viral infection: The infection cycle of Vibrio vulnificus phage VvAW1 visualized through plaque assay, electron microscopy, and proteomics

    Science.gov (United States)

    Clah, K. E. Y.; Nigro, O. D.; Miranda, J.; Schvarcz, C.; Culley, A.; Saito, M. A.; Steward, G.

    2016-02-01

    The bacterium Vibrio vulnificus is an opportunistic human pathogen that thrives in warm brackish waters. Viral infection is one of several mechanisms influencing the population dynamics of this bacterium in the natural environment. V. vulnificus-specific viruses have been isolated; however, the details of their infection cycle have not been reported. As a result, our current understanding of the interaction between the bacterium and its viruses in the environment is limited. To better understand the infection process, a strain of V. vulnificus (V93D1V) and its bacteriophage, Vibrio phage VvAW1, were isolated from the estuarine waters of the Ala Wai Canal, HI. A time-series infection experiment was conducted with the virus-host pair in which samples were collected every ten minutes for eighty minutes post-infection for analysis by plaque assay, electron microscopy, and proteomics. Using electron microscopy, visibly infected bacteria were observed forty minutes after the introduction of the virus, signaling the end of the eclipse period. The peak of infection occurred at seventy minutes with an average viral load of 78 viruses per bacterium. The percentage of visibly infected bacteria reached a maximum just prior to a rise in free viruses in the culture, indicating the end of the latent period. The percentage of infected cells that lysed was low and there was little effect on the bacterial population growth rate. Analysis of the proteome revealed that protein expression patterns, in particular capsid and other structural proteins, closely follow the timing of the observed infection cycle. Together, these analyses provided the first detailed view of a viral infection in a highly lethal aquatic bacterium. The apparent temperate nature of this virus suggests that it can be a source of mortality to V. vulnificus, but has evolved to avoid total destruction of its host by complete lysis, a characteristic that helps ensure its replication in subsequent generations.

  1. Viral etiologies of hospitalized acute lower respiratory infection patients in China, 2009-2013.

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    Luzhao Feng

    Full Text Available BACKGROUND: Acute lower respiratory infections (ALRIs are an important cause of acute illnesses and mortality worldwide and in China. However, a large-scale study on the prevalence of viral infections across multiple provinces and seasons has not been previously reported from China. Here, we aimed to identify the viral etiologies associated with ALRIs from 22 Chinese provinces. METHODS AND FINDINGS: Active surveillance for hospitalized ALRI patients in 108 sentinel hospitals in 24 provinces of China was conducted from January 2009-September 2013. We enrolled hospitalized all-age patients with ALRI, and collected respiratory specimens, blood or serum collected for diagnostic testing for respiratory syncytial virus (RSV, human influenza virus, adenoviruses (ADV, human parainfluenza virus (PIV, human metapneumovirus (hMPV, human coronavirus (hCoV and human bocavirus (hBoV. We included 28,369 ALRI patients from 81 (of the 108 sentinel hospitals in 22 (of the 24 provinces, and 10,387 (36.6% were positive for at least one etiology. The most frequently detected virus was RSV (9.9%, followed by influenza (6.6%, PIV (4.8%, ADV (3.4%, hBoV (1.9, hMPV (1.5% and hCoV (1.4%. Co-detections were found in 7.2% of patients. RSV was the most common etiology (17.0% in young children aged <2 years. Influenza viruses were the main cause of the ALRIs in adults and elderly. PIV, hBoV, hMPV and ADV infections were more frequent in children, while hCoV infection was distributed evenly in all-age. There were clear seasonal peaks for RSV, influenza, PIV, hBoV and hMPV infections. CONCLUSIONS: Our findings could serve as robust evidence for public health authorities in drawing up further plans to prevent and control ALRIs associated with viral pathogens. RSV is common in young children and prevention measures could have large public health impact. Influenza was most common in adults and influenza vaccination should be implemented on a wider scale in China.

  2. Diagnosing acute HIV infection: The performance of quantitative HIV-1 RNA testing (viral load) in the 2014 laboratory testing algorithm.

    Science.gov (United States)

    Wu, Hsiu; Cohen, Stephanie E; Westheimer, Emily; Gay, Cynthia L; Hall, Laura; Rose, Charles; Hightow-Weidman, Lisa B; Gose, Severin; Fu, Jie; Peters, Philip J

    2017-08-01

    New recommendations for laboratory diagnosis of HIV infection in the United States were published in 2014. The updated testing algorithm includes a qualitative HIV-1 RNA assay to resolve discordant immunoassay results and to identify acute HIV-1 infection (AHI). The qualitative HIV-1 RNA assay is not widely available; therefore, we evaluated the performance of a more widely available quantitative HIV-1 RNA assay, viral load, for diagnosing AHI. We determined that quantitative viral loads consistently distinguished AHI from a false-positive immunoassay result. Among 100 study participants with AHI and a viral load result, the estimated geometric mean viral load was 1,377,793copies/mL. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Human Adenovirus Core Protein V Is Targeted by the Host SUMOylation Machinery To Limit Essential Viral Functions.

    Science.gov (United States)

    Freudenberger, Nora; Meyer, Tina; Groitl, Peter; Dobner, Thomas; Schreiner, Sabrina

    2018-02-15

    Human adenoviruses (HAdV) are nonenveloped viruses containing a linear, double-stranded DNA genome surrounded by an icosahedral capsid. To allow proper viral replication, the genome is imported through the nuclear pore complex associated with viral core proteins. Until now, the role of these incoming virion proteins during the early phase of infection was poorly understood. The core protein V is speculated to bridge the core and the surrounding capsid. It binds the genome in a sequence-independent manner and localizes in the nucleus of infected cells, accumulating at nucleoli. Here, we show that protein V contains conserved SUMO conjugation motifs (SCMs). Mutation of these consensus motifs resulted in reduced SUMOylation of the protein; thus, protein V represents a novel target of the host SUMOylation machinery. To understand the role of protein V SUMO posttranslational modification during productive HAdV infection, we generated a replication-competent HAdV with SCM mutations within the protein V coding sequence. Phenotypic analyses revealed that these SCM mutations are beneficial for adenoviral replication. Blocking protein V SUMOylation at specific sites shifts the onset of viral DNA replication to earlier time points during infection and promotes viral gene expression. Simultaneously, the altered kinetics within the viral life cycle are accompanied by more efficient proteasomal degradation of host determinants and increased virus progeny production than that observed during wild-type infection. Taken together, our studies show that protein V SUMOylation reduces virus growth; hence, protein V SUMOylation represents an important novel aspect of the host antiviral strategy to limit virus replication and thereby points to potential intervention strategies. IMPORTANCE Many decades of research have revealed that HAdV structural proteins promote viral entry and mainly physical stability of the viral genome in the capsid. Our work over the last years showed that this

  4. Burden and Seasonality of Viral Acute Respiratory Tract Infections among Outpatients in Southern Sri Lanka.

    Science.gov (United States)

    Shapiro, David; Bodinayake, Champica K; Nagahawatte, Ajith; Devasiri, Vasantha; Kurukulasooriya, Ruvini; Hsiang, Jeremy; Nicholson, Bradley; De Silva, Aruna Dharshan; Østbye, Truls; Reller, Megan E; Woods, Christopher W; Tillekeratne, L Gayani

    2017-07-01

    In tropical and subtropical settings, the epidemiology of viral acute respiratory tract infections varies widely between countries. We determined the etiology, seasonality, and clinical presentation of viral acute respiratory tract infections among outpatients in southern Sri Lanka. From March 2013 to January 2015, we enrolled outpatients presenting with influenza-like illness (ILI). Nasal/nasopharyngeal samples were tested in duplicate using antigen-based rapid influenza testing and multiplex polymerase chain reaction (PCR) for respiratory viruses. Monthly proportion positive was calculated for each virus. Bivariable and multivariable logistic regression were used to identify associations between sociodemographic/clinical information and viral detection. Of 571 subjects, most (470, 82.3%) were ≥ 5 years of age and 53.1% were male. A respiratory virus was detected by PCR in 63.6% ( N = 363). Common viral etiologies included influenza (223, 39%), human enterovirus/rhinovirus (HEV/HRV, 14.5%), respiratory syncytial virus (RSV, 4.2%), and human metapneumovirus (hMPV, 3.9%). Both ILI and influenza showed clear seasonal variation, with peaks from March to June each year. RSV and hMPV activity peaked from May to July, whereas HEV/HRV was seen year-round. Patients with respiratory viruses detected were more likely to report pain with breathing (odds ratio [OR] = 2.60, P = 0.003), anorexia (OR = 2.29, P respiratory viruses detected. ILI showed clear seasonal variation in southern Sri Lanka, with most activity during March to June; peak activity was largely due to influenza. Targeted infection prevention activities such as influenza vaccination in January-February may have a large public health impact in this region.

  5. Infection of goose with genotype VIId Newcastle disease virus of goose origin elicits strong immune responses at early stage

    Directory of Open Access Journals (Sweden)

    Qianqian Xu

    2016-10-01

    Full Text Available Newcastle disease (ND, caused by virulent strains of Newcastle disease virus (NDV, is a highly contagious disease of birds that is responsible for heavy economic losses for the poultry industry worldwide. However, little is known about host-virus interactions in waterfowl, goose. In this study, we aim to characterize the host immune response in goose, based on the previous reports on the host response to NDV in chickens. Here, we evaluated viral replication and mRNA expression of 27 immune-related genes in 10 tissues of geese challenged with a genotype VIId NDV strain of goose origin (go/CH/LHLJ/1/06. The virus showed early replication, especially in digestive and immune tissues. The expression profiles showed up-regulation of Toll-like receptor (TLR1–3, 5, 7 and 15, avian β-defensin (AvBD 5–7, 10, 12 and 16, cytokines interleukin (IL-8, IL-18, IL-1β and interferon-γ, inducible NO synthase (iNOS, and MHC class I in some tissues of geese in response to NDV. In contrast, NDV infection suppressed expression of AvBD1 in cecal tonsil of geese. Moreover, we observed a highly positive correlation between viral replication and host mRNA expressions of TLR1-5 and 7, AvBD4-6, 10 and 12, all the cytokines measured, MHC class I, FAS ligand, and iNOS, mainly at 72 h post-infection. Taken together, these results demonstrated that NDV infection induces strong innate immune responses and intense inflammatory responses at early stage in goose which may associate with the viral pathogenesis.

  6. Aedes mosquito salivary immune peptides: boost or block dengue viral infections

    Directory of Open Access Journals (Sweden)

    Natthanej Luplertlop

    2014-02-01

    Full Text Available Dengue virus, one of the most important arthropod-borne viruses, infected to human can severely cause dengue hemorrhagic fever and dengue shock syndrome. There are expected about 50 million dengue infections and 500 000 individuals are hospitalized with dengue hemorrhagic fever, mainly in Southeast Asia, Pacific, and in Americas reported each year. The rapid expansion of global dengue is one of a major public health challenge, together with not yet successful solutions of dengue epidemic control strategies. Thus, these dynamic dengue viral infections exhibited high demographic, societal, and public health infrastructure impacts on human. This review aimed to highlight the current understanding of dengue mosquito immune responses and role of mosquito salivary glands on dengue infection. These information may provide a valuable knowledge of disease pathogenesis, especially in mosquito vector and dengue virus interaction, which may help to control and prevent dengue distribution.

  7. Individual co-variation between viral RNA load and gene expression reveals novel host factors during early dengue virus infection of the Aedes aegypti midgut.

    Directory of Open Access Journals (Sweden)

    Vincent Raquin

    2017-12-01

    Full Text Available Dengue virus (DENV causes more human infections than any other mosquito-borne virus. The current lack of antiviral strategies has prompted genome-wide screens for host genes that are required for DENV infectivity. Earlier transcriptomic studies that identified DENV host factors in the primary vector Aedes aegypti used inbred laboratory colonies and/or pools of mosquitoes that erase individual variation. Here, we performed transcriptome sequencing on individual midguts in a field-derived Ae. aegypti population to identify new candidate host factors modulating DENV replication. We analyzed the transcriptomic data using an approach that accounts for individual co-variation between viral RNA load and gene expression. This approach generates a prediction about the agonist or antagonist effect of candidate genes on DENV replication based on the sign of the correlation between gene expression and viral RNA load. Using this method, we identified 39 candidate genes that went undetected by conventional pairwise comparison of gene expression levels between DENV-infected midguts and uninfected controls. Only four candidate genes were detected by both methods, emphasizing their complementarity. We demonstrated the value of our approach by functional validation of a candidate agonist gene encoding a sterol regulatory element-binding protein (SREBP, which was identified by correlation analysis but not by pairwise comparison. We confirmed that SREBP promotes DENV infection in the midgut by RNAi-mediated gene knockdown in vivo. We suggest that our approach for transcriptomic analysis can empower genome-wide screens for potential agonist or antagonist factors by leveraging inter-individual variation in gene expression. More generally, this method is applicable to a wide range of phenotypic traits displaying inter-individual variation.

  8. VIRUS OF HUMAN PAPILLOMA. EPIDEMIOLOGY, LABORATORY DIAGNOSTICS AND PREVENTION OF PAPILLOMA VIRAL INFECTION

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    O. V. Narvskaya

    2011-01-01

    Full Text Available Abstract. The information reflected modern knowledge about virus of human papilloma (VHP and pathogenesis of papilloma viral infection is presented in the lecture. The actual problems of epidemiology, laboratory diagnostics and prevention of VHP associated damage of cervical epithelium have been described.

  9. An unusual renal manifestation of chronic HBV infection.

    Science.gov (United States)

    Aravindan, Ananthakrishnapuram; Yong, Jim; Killingsworth, Murray; Strasser, Simone; Suranyi, Michael

    2010-08-01

    Hepatitis B viral infection is usually a self-limiting disease in immunocompetent individuals. Chronic infection can be seen in up to 5% of infected patients. Renal manifestations of chronic HBV infection are usually glomerular. We describe here an uncommon presentation of a patient with chronic HBV infection with very high viral load and rapidly progressive renal failure. Renal biopsy showed features of tubulointerstitial nephritis and tubular epithelial inclusion bodies suggestive of HBV infection. Entecavir treatment slowed down the progression of his renal disease. Tubulointerstitial nephritis should be considered as a part of the differential diagnosis in patients with HBV infection. Early antiviral treatment may halt the progression of renal disease.

  10. Losartan and enalapril decrease viral absorption and interleukin 1 beta production by macrophages in an experimental dengue virus infection.

    Science.gov (United States)

    Hernández-Fonseca, Juan Pablo; Durán, Anyelo; Valero, Nereida; Mosquera, Jesús

    2015-11-01

    The role of angiotensin II (Ang II) in dengue virus infection remains unknown. The aim of this study was to determine the effect of losartan, an antagonist of the angiotensin II type 1 receptor (AT1 receptor), and enalapril, an inhibitor of angiotensin I-converting enzyme (ACE), on viral antigen expression and IL-1β production in peritoneal macrophages infected with dengue virus type 2. Mice treated with losartan or enalapril and untreated controls were infected intraperitoneally with the virus, and macrophages were analyzed. Infection resulted in increased IL-1β production and a high percentage of cells expressing viral antigen, and this was decreased by treatment with anti-Ang II drugs, suggesting a role for Ang II in dengue virus infection.

  11. Advances in congenital and postnatal cytomegalovirus infections

    NARCIS (Netherlands)

    Gunkel, J.

    2017-01-01

    Congenital CMV infection (cCMV) is the most prevalent viral infection worldwide and the leading cause of non-genetic sensorineural hearing loss. Early diagnosis of cCMV infection is advantageous as it allows for regular follow-up and timely intervention in case of late-onset symptoms among

  12. Perinatal and Early Childhood Environmental Factors Influencing Allergic Asthma Immunopathogenesis

    Science.gov (United States)

    Gaffin, Jonathan M.; Kanchongkittiphon, Watcharoot; Phipatanakul, Wanda

    2014-01-01

    Background The prevalence of asthma has increased dramatically over the past several decades. While hereditary factors are highly important, the rapid rise outstrips the pace of genomic variation. Great emphasis has been placed on potential modifiable early life exposures leading to childhood asthma. Methods We reviewed the recent medical literature for important studies discussing the role of the perinatal and early childhood exposures and the inception of childhood asthma. Results and Discussion Early life exposure to allergens (House dust mite (HDM), furred pets, cockroach, rodent and mold)air pollution (nitrogen dioxide (NO2), ozone (O3), volatile organic compounds (VOCs), and particulate matter (PM)) and viral respiratory tract infections (Respiratory syncytial virus (RSV) and human rhinovirus (hRV)) have been implicated in the development of asthma in high risk children. Conversely, exposure to microbial diversity in the perinatal period may diminish the development of atopy and asthma symptoms. PMID:24952205

  13. PRACTICE OF USING VIRAL PROTEASE INHIBITORS IN CHILDREN WITH HIV INFECTION

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    V.B. Denisenko

    2010-01-01

    Full Text Available Selection of the most effective and safest high-active antiretroviral therapies is a critical issue faced by modern HIV medicine. Authors studied 28 children with HIV infection aged from 3 to 7 divided into two groups administered a combination of two HIV reverse transcriptase nucleoside inhibitors with viral protease nelfinavir inhibitors (n = 13 and lopinavir/ritonavir (n = 15. The subjects in both groups demonstrated a decreased frequency of HIV-associated symptoms and opportunistic infections, positive dynamics of immunological indicators, suppression of HIV replication. When lopinavir/ritonavir was administered, there was more even better dynamics in clinical, immunological and virologic parameters, which allows this medication to be recommended as a antiretroviral therapy for children. Key words: HIV infection, lopinavir/ritonavir, nelfinavir, children. (Pediatric Pharmacology. – 2010; 7(1:62-67

  14. Clinical characteristics and viral load of respiratory syncytial virus and human metapneumovirus in children hospitaled for acute lower respiratory tract infection.

    Science.gov (United States)

    Yan, Xiao-Li; Li, Yu-Ning; Tang, Yi-Jie; Xie, Zhi-Ping; Gao, Han-Chun; Yang, Xue-Mei; Li, Yu-Mei; Liu, Li-Jun; Duan, Zhao-Jun

    2017-04-01

    Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two common viral pathogens in acute lower respiratory tract infections (ALRTI). However, the association of viral load with clinical characteristics is not well-defined in ALRTI. To explore the correlation between viral load and clinical characteristics of RSV and HMPV in children hospitalized for ALRTI in Lanzhou, China. Three hundred and eighty-seven children hospitalized for ALRTI were enrolled. Nasopharyngeal aspirates (NPAs) were sampled from each children. Real-time PCR was used to screen RSV, HMPV, and twelve additional respiratory viruses. Bronchiolitis was the leading diagnoses both in RSV and HMPV positive patients. A significantly greater frequency of wheezing (52% vs. 33.52%, P = 0.000) was noted in RSV positive and negative patients. The RSV viral load was significant higher in children aged infections (P = 0.000). No difference was found in the clinical features of HMPV positive and negative patients. The HMPV viral load had no correlation with any clinical characteristics. The incidences of severe disease were similar between single infection and coinfection for the two viruses (RSV, P = 0.221; HMPV, P = 0.764) and there has no statistical significance between severity and viral load (P = 0.166 and P = 0.721). Bronchiolitis is the most common disease caused by RSV and HMPV. High viral load or co-infection may be associated with some symptoms but neither has a significant impact on disease severity for the two viruses. J. Med. Virol. 89:589-597, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Brain transcriptomes of harbor seals demonstrate gene expression patterns of animals undergoing a metabolic disease and a viral infection

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    Stephanie M. Rosales

    2016-12-01

    Full Text Available Diseases of marine mammals can be difficult to diagnose because of their life history and protected status. Stranded marine mammals have been a particularly useful resource to discover and comprehend the diseases that plague these top predators. Additionally, advancements in high-throughput sequencing (HTS has contributed to the discovery of novel pathogens in marine mammals. In this study, we use a combination of HTS and stranded harbor seals (Phoca vitulina to better understand a known and unknown brain disease. To do this, we used transcriptomics to evaluate brain tissues from seven neonatal harbor seals that expired from an unknown cause of death (UCD and compared them to four neonatal harbor seals that had confirmed phocine herpesvirus (PhV-1 infections in the brain. Comparing the two disease states we found that UCD animals showed a significant abundance of fatty acid metabolic transcripts in their brain tissue, thus we speculate that a fatty acid metabolic dysregulation contributed to the death of these animals. Furthermore, we were able to describe the response of four young harbor seals with PhV-1 infections in the brain. PhV-1 infected animals showed a significant ability to mount an innate and adaptive immune response, especially to combat viral infections. Our data also suggests that PhV-1 can hijack host pathways for DNA packaging and exocytosis. This is the first study to use transcriptomics in marine mammals to understand host and viral interactions and assess the death of stranded marine mammals with an unknown disease. Furthermore, we show the value of applying transcriptomics on stranded marine mammals for disease characterization.

  16. Quality of Life and Adherence to Antiretroviral Drugs | Mweemba ...

    African Journals Online (AJOL)

    Efficacy of antiretroviral treatment in HIV/AIDS is showing inhibition of viral replication and reduction of viral load to a point where viral particles are undetectable in the blood of infected individuals. ... Quality of life is a complex broad ranging multidimensional concept defined in terms of individual's subjective experiences.

  17. Changing haematological parameters in dengue viral infections

    International Nuclear Information System (INIS)

    Jamil, T.; Mehmood, K.; Mujtaba, G.; Choudhry, N.

    2012-01-01

    Background: Dengue Fever is the most common arboviral disease in the world, and presents cyclically in tropical and subtropical regions of the world. The four serotypes of dengue virus, 1, 2, 3, and 4, form an antigenic subgroup of the flaviviruses (Group B arboviruses). Transmission to humans of any of these serotypes initiates a spectrum of host responses, from in apparent to severe and sometimes lethal infections. Complete Blood count (CBC) is an important part of the diagnostic workup of patients. Comparison of various finding in CBC including peripheral smear can help the physician in better management of the patient. Material and Methods: This cross sectional study was carried out on a series of suspected patients of Dengue viral infection reporting in Ittefaq Hospital (Trust). All were investigated for serological markers of acute infection. Results Out of 341 acute cases 166 (48.7%) were confirmed by IgM against Dengue virus. IgG anti-dengue was used on 200 suspected re-infected patients. Seventy-one (39.5%) were positive and 118 (59%) were negative. Among 245 confirmed dengue fever patients 43 (17.6%) were considered having dengue hemorrhagic fever on the basis of lab and clinical findings. Raised haematocrit, Leukopenia with relative Lymphocytosis and presence atypical lymphocytes along with plasmacytoid cells was consistent finding at presentation in both the patterns of disease, i.e., Dengue Haemorrhagic fever (DHF) and Dengue fever (DF). Conclusion: Changes in relative percentage of cells appear with improvement in the symptoms and recovery from the disease. These findings indicate that in the course of the disease, there are major shifts within cellular component of blood. (author)

  18. Viral DNA Sensors IFI16 and Cyclic GMP-AMP Synthase Possess Distinct Functions in Regulating Viral Gene Expression, Immune Defenses, and Apoptotic Responses during Herpesvirus Infection.

    Science.gov (United States)

    Diner, Benjamin A; Lum, Krystal K; Toettcher, Jared E; Cristea, Ileana M

    2016-11-15

    The human interferon-inducible protein IFI16 is an important antiviral factor that binds nuclear viral DNA and promotes antiviral responses. Here, we define IFI16 dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS). Live-cell imaging reveals a multiphasic IFI16 redistribution, first to viral entry sites at the nuclear periphery and then to nucleoplasmic puncta upon herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) infections. Optogenetics and live-cell microscopy establish the IFI16 pyrin domain as required for nuclear periphery localization and oligomerization. Furthermore, using proteomics, we define the signature protein interactions of the IFI16 pyrin and HIN200 domains and demonstrate the necessity of pyrin for IFI16 interactions with antiviral proteins PML and cGAS. We probe signaling pathways engaged by IFI16, cGAS, and PML using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated knockouts in primary fibroblasts. While IFI16 induces cytokines, only cGAS activates STING/TBK-1/IRF3 and apoptotic responses upon HSV-1 and HCMV infections. cGAS-dependent apoptosis upon DNA stimulation requires both the enzymatic production of cyclic dinucleotides and STING. We show that IFI16, not cGAS or PML, represses HSV-1 gene expression, reducing virus titers. This indicates that regulation of viral gene expression may function as a greater barrier to viral replication than the induction of antiviral cytokines. Altogether, our findings establish coordinated and distinct antiviral functions for IFI16 and cGAS against herpesviruses. How mammalian cells detect and respond to DNA viruses that replicate in the nucleus is poorly understood. Here, we decipher the distinct functions of two viral DNA sensors, IFI16 and cGAS, during active immune signaling upon infection with two herpesviruses, herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV). We show that IFI16

  19. Encephalitis, acute renal failure, and acute hepatitis triggered by a viral infection in an immunocompetent young adult: a case report

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    Khattab Mahmoud

    2009-11-01

    Full Text Available Abstract Introduction Cytomegalovirus generally causes self-limited, mild and asymptomatic infections in immunocompetent patients. An aggressive course in immunocompetent healthy patients is unusual. Case presentation We report the case of an immunocompetent 16-year-old Egyptian boy with encephalitis, acute renal failure, and acute hepatitis triggered by viral infection with a complete recovery following antiviral treatment. Conclusion We believe that this case adds to the understanding of the molecular biology, clinical presentation and increasing index of suspicion of many viral infections.

  20. Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages

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    Tapas K. Nayak

    2017-01-01

    Full Text Available Chikungunya virus (CHIKV infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6 MHC-I/II and B7.2 (CD86 were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology.

  1. Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages.

    Science.gov (United States)

    Nayak, Tapas K; Mamidi, Prabhudutta; Kumar, Abhishek; Singh, Laishram Pradeep K; Sahoo, Subhransu S; Chattopadhyay, Soma; Chattopadhyay, Subhasis

    2017-01-06

    Chikungunya virus (CHIKV) infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6) MHC-I/II and B7.2 (CD86) were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology.

  2. The Effects of Viral Load Burden on Pregnancy Loss among HIV-Infected Women in the United States

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    Jordan E. Cates

    2015-01-01

    Full Text Available Background. To evaluate the effects of HIV viral load, measured cross-sectionally and cumulatively, on the risk of miscarriage or stillbirth (pregnancy loss among HIV-infected women enrolled in the Women’s Interagency HIV Study between 1994 and 2013. Methods. We assessed three exposures: most recent viral load measure before the pregnancy ended, log10 copy-years viremia from initiation of antiretroviral therapy (ART to conception, and log10 copy-years viremia in the two years before conception. Results. The risk of pregnancy loss for those with log10 viral load >4.00 before pregnancy ended was 1.59 (95% confidence interval (CI: 0.99, 2.56 times as high as the risk for women whose log10 viral load was ≤1.60. There was not a meaningful impact of log10 copy-years viremia since ART or log10 copy-years viremia in the two years before conception on pregnancy loss (adjusted risk ratios (aRRs: 0.80 (95% CI: 0.69, 0.92 and 1.00 (95% CI: 0.90, 1.11, resp.. Conclusions. Cumulative viral load burden does not appear to be an informative measure for pregnancy loss risk, but the extent of HIV replication during pregnancy, as represented by plasma HIV RNA viral load, predicted loss versus live birth in this ethnically diverse cohort of HIV-infected US women.

  3. The Effects of Viral Load Burden on Pregnancy Loss among HIV-Infected Women in the United States.

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    Cates, Jordan E; Westreich, Daniel; Edmonds, Andrew; Wright, Rodney L; Minkoff, Howard; Colie, Christine; Greenblatt, Ruth M; Cejtin, Helen E; Karim, Roksana; Haddad, Lisa B; Kempf, Mirjam-Colette; Golub, Elizabeth T; Adimora, Adaora A

    2015-01-01

    To evaluate the effects of HIV viral load, measured cross-sectionally and cumulatively, on the risk of miscarriage or stillbirth (pregnancy loss) among HIV-infected women enrolled in the Women's Interagency HIV Study between 1994 and 2013. We assessed three exposures: most recent viral load measure before the pregnancy ended, log10 copy-years viremia from initiation of antiretroviral therapy (ART) to conception, and log10 copy-years viremia in the two years before conception. The risk of pregnancy loss for those with log10 viral load >4.00 before pregnancy ended was 1.59 (95% confidence interval (CI): 0.99, 2.56) times as high as the risk for women whose log10 viral load was ≤1.60. There was not a meaningful impact of log10 copy-years viremia since ART or log10 copy-years viremia in the two years before conception on pregnancy loss (adjusted risk ratios (aRRs): 0.80 (95% CI: 0.69, 0.92) and 1.00 (95% CI: 0.90, 1.11), resp.). Cumulative viral load burden does not appear to be an informative measure for pregnancy loss risk, but the extent of HIV replication during pregnancy, as represented by plasma HIV RNA viral load, predicted loss versus live birth in this ethnically diverse cohort of HIV-infected US women.

  4. HCMV Reprogramming of Infected Monocyte Survival and Differentiation: A Goldilocks Phenomenon

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    Emily V. Stevenson

    2014-02-01

    Full Text Available The wide range of disease pathologies seen in multiple organ sites associated with human cytomegalovirus (HCMV infection results from the systemic hematogenous dissemination of the virus, which is mediated predominately by infected monocytes. In addition to their role in viral spread, infected monocytes are also known to play a key role in viral latency and life-long persistence. However, in order to utilize infected monocytes for viral spread and persistence, HCMV must overcome a number of monocyte biological hurdles, including their naturally short lifespan and their inability to support viral gene expression and replication. Our laboratory has shown that HCMV is able to manipulate the biology of infected monocytes in order to overcome these biological hurdles by inducing the survival and differentiation of infected monocytes into long-lived macrophages capable of supporting viral gene expression and replication. In this current review, we describe the unique aspects of how HCMV promotes monocyte survival and differentiation by inducing a “finely-tuned” macrophage cell type following infection. Specifically, we describe the induction of a uniquely polarized macrophage subset from infected monocytes, which we argue is the ideal cellular environment for the initiation of viral gene expression and replication and, ultimately, viral spread and persistence within the infected host.

  5. Time to viral load suppression in antiretroviral-naive and -experienced HIV-infected pregnant women on highly active antiretroviral therapy: implications for pregnant women presenting late in gestation.

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    Aziz, N; Sokoloff, A; Kornak, J; Leva, N V; Mendiola, M L; Levison, J; Feakins, C; Shannon, M; Cohan, D

    2013-11-01

    To compare time to achieve viral load HIV-infected antiretroviral (ARV) -naive versus ARV-experienced pregnant women on highly active antiretroviral therapy (HAART). Retrospective cohort study. Three university medical centers, USA. HIV-infected pregnant women initiated or restarted on HAART during pregnancy. We calculated time to viral load HIV-infected pregnant women on HAART who reported at least 50% adherence, stratifying based on previous ARV exposure history. Time to HIV viral load HIV-infected pregnant women, comprising 76 ARV-naive and 62 ARV-experienced. Ninety-three percent of ARV-naive women achieved a viral load HIV log10 viral load was associated with a later time of achieving viral load HIV log10 viral load was associated with a longer time of achieving viral load Pregnant women with ≥50% adherence, whether ARV-naive or ARV-experienced, on average achieve a viral load HIV log10 viral load were all statistically significant predictors of earlier time to achieve viral load <400 copies/ml and <1000 copies/ml. Increased CD4 count was statistically significant as a predictor of earlier time to achieve viral load <1000 copies/ml. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.

  6. Improving dengue viral antigens detection in dengue patient serum specimens using a low pH glycine buffer treatment.

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    Shen, Wen-Fan; Galula, Jedhan Ucat; Chang, Gwong-Jen J; Wu, Han-Chung; King, Chwan-Chuen; Chao, Day-Yu

    2017-04-01

    Early diagnosis of dengue virus (DENV) infection to monitor the potential progression to hemorrhagic fever can influence the timely management of dengue-associated severe illness. Nonstructural protein 1 (NS1) antigen detection in acute serum specimens has been widely accepted as an early diagnostic assay for dengue infection; however, lower sensitivity of the NS1 antigen-capture enzyme-linked immunosorbent assay (Ag-ELISA) in secondary dengue viral infection has been reported. In this study, we developed two forms of Ag-ELISA capable of detecting E-Ag containing virion and virus-like particles, and secreted NS1 (sNS1) antigens, respectively. The temporal kinetics of viral RNA, sNS1, and E-Ag were evaluated based on the in vitro infection experiment. Meanwhile, a panel of 62 DENV-2 infected patients' sera was tested. The sensitivity was 3.042 ng/mL and 3.840 ng/mL for sNS1 and E, respectively. The temporal kinetics of the appearance of viral RNA, E, NS1, and infectious virus in virus-infected tissue culture media suggested that viral RNAs and NS1 antigens could be detected earlier than E-Ag and infectious virus. Furthermore, a panel of 62 sera from patients infected by DENV Serotype 2 was tested. Treating clinical specimens with the dissociation buffer increased the detectable level of E from 13% to 92% and NS1 antigens from 40% to 85%. Inclusion of a low-pH glycine buffer treatment step in the commercially available Ag-ELISA is crucial for clinical diagnosis and E-containing viral particles could be a valuable target for acute DENV diagnosis, similar to NS1 detection. Copyright © 2015. Published by Elsevier B.V.

  7. Identification of Proteins Bound to Dengue Viral RNA In Vivo Reveals New Host Proteins Important for Virus Replication

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    Stacia L. Phillips

    2016-01-01

    Full Text Available Dengue virus is the most prevalent cause of arthropod-borne infection worldwide. Due to the limited coding capacity of the viral genome and the complexity of the viral life cycle, host cell proteins play essential roles throughout the course of viral infection. Host RNA-binding proteins mediate various aspects of virus replication through their physical interactions with viral RNA. Here we describe a technique designed to identify such interactions in the context of infected cells using UV cross-linking followed by antisense-mediated affinity purification and mass spectrometry. Using this approach, we identified interactions, several of them novel, between host proteins and dengue viral RNA in infected Huh7 cells. Most of these interactions were subsequently validated using RNA immunoprecipitation. Using small interfering RNA (siRNA-mediated gene silencing, we showed that more than half of these host proteins are likely involved in regulating virus replication, demonstrating the utility of this method in identifying biologically relevant interactions that may not be identified using traditional in vitro approaches.

  8. siRNA as an alternative therapy against viral infections

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    Hana A. Pawestri

    2012-07-01

    mutating, multiple siRNAs have to be used that target different sequences of the viral RNA. Still, siRNA therapy is facing some difficulties such as the specialized delivery to the infected tissue and the siRNA protection from the digestion by nucleases. These problems will have to be solved before siRNA therapy could be used in clinical trials.. Based on several researches, siRNA could be used as an alternative therapy against life threatening viruses. This therapy is recommended to be tested further in clinical trials with respect to several aspects, such as design of siRNA and transfer mechanism. (Health Science Indones 2010; 1: 58 - 65

  9. Quality of life and adherence to treatment of patients with chronic viral hepatitis C

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    Mirkhaydarov R.Sh.

    2018-04-01

    Full Text Available Background. The problem of viral hepatitis C in the modern world is rather acute for public health service. The patients themselves, their striving for recovery, desire to have the quality of live on the same level as a healthy person has and the understanding of the necessity to obey the a doctor’s recommendations play the significant role in the successful treatment of this disease. The aim of the given work is the study of the quality of life and the adherence to treatment of young people with chronic viral hepatitis C and the following analysis of the results. Materials and methods. In the process of research, 138 men at the age of 18–45 with chronic viral hepatitis were ex- amined. The verification of the diagnosis occurred on the basis of international classification of chronic hepatitis (Los Angeles, 1994, and also ICD10 (B17.1, besides, the HCV RNA for more than 6 months was also taken into account. Twenty-five apparently healthy men 18–45 years old were included in this group. The quality of life was clarified with the help of short form of the adapted Russified specialized questionnaire “Medical Outcomes Study, Short Form” (SF36 Health Study Survey. Statistical data processing was carried out with the use of application package “Statistica for Windows”, version 7.0. Results. The minimum index in the group of the patients with chronical viral hepatitis C was the index of social activity (SF – 46.2 ± 0.8 points. In this group, the index of physical pain (BP was at its maximum. The study of the adherence to treatment depending on the quality of life stays acute. Conclusions. During the course of this work, the peculiarities of the quality of life scales were determined according to the SF-36 Health Study Survey among the patients with chronic viral hepatitis C and the correlations with the adher- ence to treatment.

  10. The stress granule component TIA-1 binds tick-borne encephalitis virus RNA and is recruited to perinuclear sites of viral replication to inhibit viral translation.

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    Albornoz, Amelina; Carletti, Tea; Corazza, Gianmarco; Marcello, Alessandro

    2014-06-01

    Flaviviruses are a major cause of disease in humans and animals worldwide. Tick-borne encephalitis virus (TBEV) is the most important arthropod-borne flavivirus endemic in Europe and is the etiological agent of tick-borne encephalitis, a potentially fatal infection of the central nervous system. However, the contributions of host proteins during TBEV infection are poorly understood. In this work, we investigate the cellular protein TIA-1 and its cognate factor TIAR, which are stress-induced RNA-binding proteins involved in the repression of initiation of translation of cellular mRNAs and in the formation of stress granules. We show that TIA-1 and TIAR interact with viral RNA in TBEV-infected cells. During TBEV infection, cytoplasmic TIA-1 and TIAR are recruited at sites of viral replication with concomitant depletion from stress granules. This effect is specific, since G3BP1, another component of these cytoplasmic structures, remains localized to stress granules. Moreover, heat shock induction of stress granules containing TIA-1, but not G3BP1, is inhibited in TBEV-infected cells. Infection of cells depleted of TIA-1 or TIAR by small interfering RNA (siRNA) or TIA-1(-/-) mouse fibroblasts, leads to a significant increase in TBEV extracellular infectivity. Interestingly, TIAR(-/-) fibroblasts show the opposite effect on TBEV infection, and this phenotype appears to be related to an excess of TIA-1 in these cells. Taking advantage of a TBE-luciferase replicon system, we also observed increased luciferase activity in TIA-1(-/-) mouse fibroblasts at early time points, consistent with TIA-1-mediated inhibition at the level of the first round of viral translation. These results indicate that, in response to TBEV infection, TIA-1 is recruited to sites of virus replication to bind TBEV RNA and modulate viral translation independently of stress granule (SG) formation. This study (i) extends previous work that showed TIA-1/TIAR recruitment at sites of flavivirus replication

  11. Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection

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    Marcia Bellon

    2017-10-01

    Full Text Available The progressive loss of immunological memory during aging correlates with a reduced proliferative capacity and shortened telomeres of T cells. Growing evidence suggests that this phenotype is recapitulated during chronic viral infection. The antigenic volume imposed by persistent and latent viruses exposes the immune system to unique challenges that lead to host T-cell exhaustion, characterized by impaired T-cell functions. These dysfunctional memory T cells lack telomerase, the protein capable of extending and stabilizing chromosome ends, imposing constraints on telomere dynamics. A deleterious consequence of this excessive telomere shortening is the premature induction of replicative senescence of viral-specific CD8+ memory T cells. While senescent cells are unable to expand, they can survive for extended periods of time and are more resistant to apoptotic signals. This review takes a closer look at T-cell exhaustion in chronic viruses known to cause human disease: Epstein–Barr virus (EBV, Hepatitis B/C/D virus (HBV/HCV/HDV, human herpesvirus 8 (HHV-8, human immunodeficiency virus (HIV, human T-cell leukemia virus type I (HTLV-I, human papillomavirus (HPV, herpes simplex virus-1/2(HSV-1/2, and Varicella–Zoster virus (VZV. Current literature linking T-cell exhaustion with critical telomere lengths and immune senescence are discussed. The concept that enduring antigen stimulation leads to T-cell exhaustion that favors telomere attrition and a cell fate marked by enhanced T-cell senescence appears to be a common endpoint to chronic viral infections.

  12. Re-localization of Cellular Protein SRp20 during Poliovirus Infection: Bridging a Viral IRES to the Host Cell Translation Apparatus

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    Fitzgerald, Kerry D.; Semler, Bert L.

    2011-01-01

    Poliovirus IRES-mediated translation requires the functions of certain canonical as well as non-canonical factors for the recruitment of ribosomes t