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Sample records for syndrome virus structural

  1. A 3D model of the membrane protein complex formed by the white spot syndrome virus structural proteins.

    Directory of Open Access Journals (Sweden)

    Yun-Shiang Chang

    Full Text Available BACKGROUND: Outbreaks of white spot disease have had a large negative economic impact on cultured shrimp worldwide. However, the pathogenesis of the causative virus, WSSV (whit spot syndrome virus, is not yet well understood. WSSV is a large enveloped virus. The WSSV virion has three structural layers surrounding its core DNA: an outer envelope, a tegument and a nucleocapsid. In this study, we investigated the protein-protein interactions of the major WSSV structural proteins, including several envelope and tegument proteins that are known to be involved in the infection process. PRINCIPAL FINDINGS: In the present report, we used coimmunoprecipitation and yeast two-hybrid assays to elucidate and/or confirm all the interactions that occur among the WSSV structural (envelope and tegument proteins VP51A, VP19, VP24, VP26 and VP28. We found that VP51A interacted directly not only with VP26 but also with VP19 and VP24. VP51A, VP19 and VP24 were also shown to have an affinity for self-interaction. Chemical cross-linking assays showed that these three self-interacting proteins could occur as dimers. CONCLUSIONS: From our present results in conjunction with other previously established interactions we construct a 3D model in which VP24 acts as a core protein that directly associates with VP26, VP28, VP38A, VP51A and WSV010 to form a membrane-associated protein complex. VP19 and VP37 are attached to this complex via association with VP51A and VP28, respectively. Through the VP26-VP51C interaction this envelope complex is anchored to the nucleocapsid, which is made of layers of rings formed by VP664. A 3D model of the nucleocapsid and the surrounding outer membrane is presented.

  2. Roles of viroplasm-like structures formed by nonstructural protein NSs in infection with severe fever with thrombocytopenia syndrome virus.

    Science.gov (United States)

    Wu, Xiaodong; Qi, Xian; Liang, Mifang; Li, Chuan; Cardona, Carol J; Li, Dexin; Xing, Zheng

    2014-06-01

    Severe fever with thrombocytopenia syndrome (SFTS) virus is an emerging bunyavirus that causes a hemorrhagic fever with a high mortality rate. The virus is likely tick-borne and replicates primarily in hemopoietic cells, which may lead to disregulation of proinflammatory cytokine induction and loss of leukocytes and platelets. The viral genome contains L, M, and S segments encoding a viral RNA polymerase, glycoproteins G(n) and G(c), nucleoprotein (NP), and a nonstructural S segment (NSs) protein. NSs protein is involved in the regulation of host innate immune responses and suppression of IFNβ-promoter activities. In this article, we demonstrate that NSs protein can form viroplasm-like structures (VLSs) in infected and transfected cells. NSs protein molecules interact with one another, interact with NP, and were associated with viral RNA in infected cells, suggesting that NSs protein may be involved in viral replication. Furthermore, we observed that NSs-formed VLS colocalized with lipid droplets and that inhibitors of fatty acid biosynthesis decreased VLS formation or viral replication in transfected and infected cells. Finally, we have demonstrated that viral dsRNAs were also localized in VLS in infected cells, suggesting that NSs-formed VLS may be implicated in the replication of SFTS bunyavirus. These findings identify a novel function of nonstructural NSs in SFTSV-infected cells where it is a scaffolding component in a VLS functioning as a virus replication factory. This function is in addition to the role of NSs protein in modulating host responses that will broaden our understanding of viral pathogenesis of phleboviruses. © FASEB.

  3. Multiple proteins of White spot syndrome virus involved in ...

    Indian Academy of Sciences (India)

    The recognition and attachment of virus to its host cell surface is a critical step for viral infection. Recent research revealed that -integrin was involved in White spot syndrome virus (WSSV) infection. In this study, the interaction of -integrin with structure proteins of WSSV and motifs involved in WSSV infection was ...

  4. Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)

    DEFF Research Database (Denmark)

    Kvisgaard, Lise Kirstine

    This PhD thesis presents the diversity of Porcine Reproductive and Respiratory Syndrome viruses (PRRSV) circulating in the Danish pig population. PRRS is a disease in pigs caused by the PRRS virus resulting in reproductive failures in sows and gilts and respiratory diseases in pigs . Due to genetic...

  5. The non-structural protein 5 and matrix protein are antigenic targets of T cell immunity to genotype 1 porcine reproductive and respiratory syndrome viruses

    Directory of Open Access Journals (Sweden)

    Helen eMokhtar

    2016-02-01

    Full Text Available The porcine reproductive and respiratory syndrome virus (PRRSV is the cause of one of the most economically important diseases affecting swine worldwide. Efforts to develop a next-generation vaccine have largely focussed on envelope glycoproteins to target virus-neutralising antibody responses. However, these approaches have failed to demonstrate the necessary efficacy to progress towards market. T cells are crucial to the control of many viruses through cytolysis and cytokine secretion. Since control of PRRSV infection is not dependent on the development of neutralising antibodies, it has been proposed that T cell mediated immunity plays a key role. We therefore hypothesised that conserved T cell antigens represent prime candidates for the development a novel PRRS vaccine. Antigens were identified by screening a proteome-wide synthetic peptide library with T cells from cohorts of pigs rendered immune by experimental infections with a closely-related (subtype 1 or divergent (subtype 3 PRRSV-1 strain. Dominant T cell IFN-γ responses were directed against the non-structural protein 5 (NSP5, and to a lesser extent, the matrix (M protein. The majority of NSP5-specific CD8 T cells and M-specific CD4 T cells expressed a putative effector memory phenotype and were polyfunctional as assessed by co-expression of TNF-α and mobilisation of the cytotoxic degranulation marker CD107a. Both antigens were generally well conserved amongst strains of both PRRSV genotypes. Thus M and NSP5 represent attractive vaccine candidate T cell antigens which should be evaluated further in the context of PRRSV vaccine development.

  6. Porcine reproductive and respiratory syndrome virus (PRRSV): pathogenesis and interaction with the immune System

    Science.gov (United States)

    This review addresses important issues of porcine reproductive and respiratory syndrome virus (PRRSV) infection, immunity, pathogenesis and control. Worldwide PRRS is the most economically important infectious disease of pigs. We highlight the latest information on viral genome structure, pathogenic...

  7. The Non-structural Protein 5 and Matrix Protein Are Antigenic Targets of T Cell Immunity to Genotype 1 Porcine Reproductive and Respiratory Syndrome Viruses

    DEFF Research Database (Denmark)

    Mokhtar, Helen; Pedrera, Miriam; Frossard, Jean-Pierre

    2016-01-01

    The porcine reproductive and respiratory syndrome virus (PRRSV) is the cause of one of the most economically important diseases affecting swine worldwide. Efforts to develop a next-generation vaccine have largely focused on envelope glycoproteins to target virus-neutralizing antibody responses...... proposed that T cell-mediated immunity plays a key role. Therefore, we hypothesized that conserved T cell antigens represent prime candidates for the development a novel PRRS vaccine. Antigens were identified by screening a proteome-wide synthetic peptide library with T cells from cohorts of pigs rendered...... attractive vaccine candidate T cell antigens, which should be evaluated further in the context of PRRSV vaccine development....

  8. Efficacy of double-stranded RNA against white spot syndrome virus (WSSV non-structural (orf89, wsv191 and structural (vp28, vp26 genes in the Pacific white shrimp Litopenaeus vannamei

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    César M. Escobedo-Bonilla

    2015-04-01

    Full Text Available White spot syndrome virus (WSSV is a major pathogen in shrimp aquaculture. RNA interference (RNAi is a promising tool against viral infections. Previous works with RNAi showed different antiviral efficacies depending on the silenced gene. This work evaluated the antiviral efficacy of double-stranded (ds RNA against two non-structural (orf89, wsv191 WSSV genes compared to structural (vp26, vp28 genes to inhibit an experimental WSSV infection. Gene orf89 encodes a putative regulatory protein and gene white spot virus (wsv191 encodes a nonspecific nuclease; whereas genes vp26 and vp28 encode envelope proteins, respectively. Molecules of dsRNA against each of the WSSV genes were intramuscularly injected (4 μg per shrimp into a group of shrimp 48 h before a WSSV challenge. The highest antiviral activity occurred with dsRNA against orf89, vp28 and vp26 (cumulative mortalities 10%, 10% and 21%, respectively. In contrast, the least effective treatment was wsv191 dsRNA (cumulative mortality 83%. All dead animals were WSSV-positive by one-step PCR, whereas reverse-transcription PCR of all surviving shrimp confirmed inhibition of virus replication. This study showed that dsRNA against WSSV genes orf89, vp28 and vp26 were highly effective to inhibit virus replication and suggest an essential role in WSSV infection. Non-structural WSSV genes such as orf89 can be used as novel targets to design therapeutic RNAi molecules against WSSV infection.

  9. Generation of recombinant monoclonal antibodies to study structure-function of envelope protein VP28 of white spot syndrome virus from shrimp

    International Nuclear Information System (INIS)

    Wang Yuzhen; Zhang Xiaohua; Yuan Li; Xu Tao; Rao Yu; Li Jia; Dai Heping

    2008-01-01

    White spot syndrome virus (WSSV) is a major pathogen in shrimp aquaculture. VP28 is one of the most important envelope proteins of WSSV. In this study, a recombinant antibody library, as single-chain fragment variable (scFv) format, displayed on phage was constructed using mRNA from spleen cells of mice immunized with full-length VP28 expressed in Escherichia coli. After several rounds of panning, six scFv antibodies specifically binding to the epitopes in the N-terminal, middle, and C-terminal regions of VP28, respectively, were isolated from the library. Using these scFv antibodies as tools, the epitopes in VP28 were located on the envelope of the virion by immuno-electron microscopy. Neutralization assay with these antibodies in vitro suggested that these epitopes may not be the attachment site of WSSV to host cell receptor. This study provides a new way to investigate the structure and function of the envelope proteins of WSSV

  10. Structure of viruses: a short history.

    Science.gov (United States)

    Rossmann, Michael G

    2013-05-01

    This review is a partially personal account of the discovery of virus structure and its implication for virus function. Although I have endeavored to cover all aspects of structural virology and to acknowledge relevant individuals, I know that I have favored taking examples from my own experience in telling this story. I am anxious to apologize to all those who I might have unintentionally offended by omitting their work. The first knowledge of virus structure was a result of Stanley's studies of tobacco mosaic virus (TMV) and the subsequent X-ray fiber diffraction analysis by Bernal and Fankuchen in the 1930s. At about the same time it became apparent that crystals of small RNA plant and animal viruses could diffract X-rays, demonstrating that viruses must have distinct and unique structures. More advances were made in the 1950s with the realization by Watson and Crick that viruses might have icosahedral symmetry. With the improvement of experimental and computational techniques in the 1970s, it became possible to determine the three-dimensional, near-atomic resolution structures of some small icosahedral plant and animal RNA viruses. It was a great surprise that the protecting capsids of the first virus structures to be determined had the same architecture. The capsid proteins of these viruses all had a 'jelly-roll' fold and, furthermore, the organization of the capsid protein in the virus were similar, suggesting a common ancestral virus from which many of today's viruses have evolved. By this time a more detailed structure of TMV had also been established, but both the architecture and capsid protein fold were quite different to that of the icosahedral viruses. The small icosahedral RNA virus structures were also informative of how and where cellular receptors, anti-viral compounds, and neutralizing antibodies bound to these viruses. However, larger lipid membrane enveloped viruses did not form sufficiently ordered crystals to obtain good X-ray diffraction

  11. Immune defence White Spot Syndrome Virus infected shrimp, Penaeus monodon

    NARCIS (Netherlands)

    Arts, J.A.J.

    2006-01-01

    White spot syndrome virus (WSSV) is the most important viral pathogen of cultured penaeid shrimp worldwide. Since the initial discovery of the virus inTaiwanin 1992, it has spread to shrimp farming regions in Southeast Asia, the

  12. Archaeal Viruses: Diversity, Replication, and Structure.

    Science.gov (United States)

    Dellas, Nikki; Snyder, Jamie C; Bolduc, Benjamin; Young, Mark J

    2014-11-01

    The Archaea-and their viruses-remain the most enigmatic of life's three domains. Once thought to inhabit only extreme environments, archaea are now known to inhabit diverse environments. Even though the first archaeal virus was described over 40 years ago, only 117 archaeal viruses have been discovered to date. Despite this small number, these viruses have painted a portrait of enormous morphological and genetic diversity. For example, research centered around the various steps of the archaeal virus life cycle has led to the discovery of unique mechanisms employed by archaeal viruses during replication, maturation, and virion release. In many instances, archaeal virus proteins display very low levels of sequence homology to other proteins listed in the public database, and therefore, structural characterization of these proteins has played an integral role in functional assignment. These structural studies have not only provided insights into structure-function relationships but have also identified links between viruses across all three domains of life.

  13. Protection of Penaeus monodon against white spot syndrome virus using a WSSV subunit vaccine

    NARCIS (Netherlands)

    Witteveldt, J.; Vlak, J.M.; Hulten, van M.C.W.

    2004-01-01

    Although invertebrates lack a true adaptive immune response, the potential to vaccinate Penaeus monodon shrimp against white spot syndrome virus (WSSV) using the WSSV envelope proteins VP19 and VP28 was evaluated. Both structural WSSV proteins were N-terminally fused to the maltose binding protein

  14. Nucleocapsid protein VP15 is the basic DNA binding protein of white spot syndrome virus of shrimp

    NARCIS (Netherlands)

    Witteveldt, J.; Vermeesch, A.M.G.; Langenhof, M.; Lang, de A.; Vlak, J.M.; Hulten, van M.C.W.

    2005-01-01

    White spot syndrome virus (WSSV) is type species of the genus Whispovirus of the new family Nimaviridae. Despite the elucidation of its genomic sequence, very little is known about the virus as only 6% of its ORFs show homology to known genes. One of the structural virion proteins, VP15, is part of

  15. Secondary Hemophagocytic Syndrome Associated with Herpes Virus Infections

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    S. R. Rodionovskaya

    2015-01-01

    Full Text Available Hemophagocytic syndrome is one of the complications of herpes virus infections. Here, we describe the case of a 8—year-old male with secondary hemophagocytic syndrome. The disease was diagnosed in the early stages. The patient received treatment with dexamethasone, intravenous immunoglobulin, which has led to a weakening of the ignition and the suppression of the disease with rapid treatment.

  16. White Spot Syndrome Virus infection in Penaeus monodon is ...

    Indian Academy of Sciences (India)

    White Spot Syndrome Virus (WSSV) is a major pathogen in shrimp aquaculture, and its rampant spread has resulted in great economic loss. Identification of host cellular proteins interacting with WSSV will help in unravelling the repertoire of host proteins involved in WSSV infection. In this study, we have employed ...

  17. Quantification of virus syndrome in chili peppers

    African Journals Online (AJOL)

    Jane

    2011-06-15

    Jun 15, 2011 ... alternative for the quantification of the disease' syndromes in regards to this crop. The result of these ..... parison of treatments such as cultivars or control measures and ..... Vascular discoloration and stem necrosis. 2.

  18. New Respiratory Viruses in Infants with Bronchoobstructive Syndrome

    OpenAIRE

    S.M. Rudenko; O.V. Obertynska; Yu.O. Boyko; O.M. Okhotnikova; I.V. Dzyublik

    2014-01-01

    The objective of our study was to identify new respiratory viruses in infants with bronchoobstructive syndrome (obstructive bronchitis and exacerbation of bronchial asthma). We examined 28 children aged from 5 months to 6 years. The average age of the patients was 33.7 months (95% CI 24.5–43.0). Viruses have been identified in 75 % of patients. In 39.3 % we found bocavirus. Metapneumovirus was detected in 10.7 % of patients. Exacerbation of bronchial asthma 2.3 times more likely was associate...

  19. Burning mouth syndrome due to herpes simplex virus type 1.

    Science.gov (United States)

    Nagel, Maria A; Choe, Alexander; Traktinskiy, Igor; Gilden, Don

    2015-04-01

    Burning mouth syndrome is characterised by chronic orofacial burning pain. No dental or medical cause has been found. We present a case of burning mouth syndrome of 6 months duration in a healthy 65-year-old woman, which was associated with high copy numbers of herpes simplex virus type 1 (HSV-1) DNA in the saliva. Her pain resolved completely after antiviral treatment with a corresponding absence of salivary HSV-1 DNA 4 weeks and 6 months later. 2015 BMJ Publishing Group Ltd.

  20. Syndromic surveillance for West Nile virus using raptors in rehabilitation.

    Science.gov (United States)

    Ana, Alba; Perez Andrés, M; Julia, Ponder; Pedro, Puig; Arno, Wünschmann; Kimberly, Vander Waal; Julio, Alvarez; Michelle, Willette

    2017-11-29

    Wildlife rehabilitation centers routinely gather health-related data from diverse species. Their capability to signal the occurrence of emerging pathogens and improve traditional surveillance remains largely unexplored. This paper assessed the utility for syndromic surveillance of raptors admitted to The Raptor Center (TRC) to signal circulation of West Nile Virus (WNV) in Minnesota between 1990 and 2014. An exhaustive descriptive analysis using grouping time series structures and models of interrupted times series was conducted for indicator subsets. A total of 13,080 raptors were monitored. The most representative species were red-tailed hawks, great horned owls, Cooper's hawks, American kestrels and bald eagles. Results indicated that temporal patterns of accessions at the TRC changed distinctively after the incursion of WNV in 2002. The frequency of hawks showing WNV-like signs increased almost 3 times during July and August, suggesting that monitoring of hawks admitted to TRC with WNV-like signs could serve as an indicator of WNV circulation. These findings were also supported by the results of laboratory diagnosis. This study demonstrates that monitoring of data routinely collected by wildlife rehabilitation centers has the potential to signal the spread of pathogens that may affect wild, domestic animals and humans, thus supporting the early detection of disease incursions in a region and monitoring of disease trends. Ultimately, data collected in rehabilitation centers may provide insights to efficiently allocate financial and human resources on disease prevention and surveillance.

  1. Epstein-Barr Virus (EBV-associated Haemophagocytic Syndrome

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    Lorenza Torti

    2012-01-01

    Full Text Available We describe the case of a 17- year old female who developed fatal haemophagocytic syndrome (HPS one month following acute infection caused by Epstein-Barr virus (EBV. Despite initiation of treatment and reduction of EBV load, laboratory signs of HPS as severe cytopenia, hypofibrinogenemia, hyperferritinemia and hypertriglyceridemia persisted, and the patient died of multiorgan failure. HPS is a rare, but life-threatening complication of EBV infection.

  2. New Respiratory Viruses in Infants with Bronchoobstructive Syndrome

    Directory of Open Access Journals (Sweden)

    S.M. Rudenko

    2014-05-01

    Full Text Available The objective of our study was to identify new respiratory viruses in infants with bronchoobstructive syndrome (obstructive bronchitis and exacerbation of bronchial asthma. We examined 28 children aged from 5 months to 6 years. The average age of the patients was 33.7 months (95% CI 24.5–43.0. Viruses have been identified in 75 % of patients. In 39.3 % we found bocavirus. Metapneumovirus was detected in 10.7 % of patients. Exacerbation of bronchial asthma 2.3 times more likely was associated with bocavirus infection compared to patients with obstructive bronchitis (RR = 2.3 (95% CI 0.9–6.2. Duration of bronchoobstructive syndrome in children with bronchial asthma was significantly higher (p < 0.0001 than in children with obstructive bronchitis — 5.3 days (95% CI 4.1–6.4 versus 2.7 days (95% CI 2.3–3.1. The findings confirm a significant role of viral infection and new respiratory viruses in causing bronchoobstructive syndrome in children.

  3. White spot syndrome virus inactivation study by using gamma irradiation

    Science.gov (United States)

    Heidareh, Marzieh; Sedeh, Farahnaz Motamedi; Soltani, Mehdi; Rajabifar, Saeed; Afsharnasab, Mohammad; Dashtiannasab, Aghil

    2014-09-01

    The present study was conducted to investigate the effect of gamma irradiation on white spot syndrome virus (WSSV). White spot syndrome virus is a pathogen of major economic importance in cultured penaeid shrimp industries. White spot disease can cause mortalities reaching 100% within 3-10 days of gross signs appearing. During the period of culture, immunostimulant agents and vaccines may provide potential methods to protect shrimps from opportunistic and pathogenic microrganisms. In this study, firstly, WSSV was isolated from infected shrimp and then multiplied in crayfish. WSSV was purified from the infected crayfish haemolymph by sucrose gradient and confirmed by transmission electron microscopy. In vivo virus titration was performed in shrimp, Penaeus semisulcatus. The LD50 of live virus stock was calculated 10 5.4/mL. Shrimp post-larvae (1-2 g) were treated with gamma-irradiated (different doses) WSSV (100 to 10-4 dilutions) for a period of 10 days. The dose/survival curve for irradiated and un-irradiated WSSV was drawn; the optimum dose range for inactivation of WSSV and unaltered antigenicity was obtained 14-15 kGy. This preliminary information suggests that shrimp appear to benefit from treatment with gammairradiated WSSV especially at 14-15 KGy.

  4. Detection of Herpes Simplex Virus DNA in Pseudoexfoliation Syndrome

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    Masoomeh Eghtedari

    2009-06-01

    Full Text Available Background: Pseudoexfoliation syndrome is one of the mostcommon identifiable causes of open angle glaucoma. It hasunknown etiology and pathogenesis. Infection, possibly viral,is one of the proposed pathogenic mechanisms in this condition.In the present study the presence of herpes simplex virus(HSV in specimens of anterior lens capsule of patients withpseudoexfoliation syndrome has been assessed.Methods: The presence of HSV- DNA was searched by usingpolymerase chain reaction method in specimens of anteriorlens capsule (5 mm diameter of 50 patients with pseudoexfoliationsyndrome (study group and 50 age-matchedpatients without the disease (control group who underwentcataract or combined cataract and glaucoma surgery duringa one-year (2006-2007 period in Khalili Hospital, Shiraz,Iran. The results were compared statistically with Chisquaretest and independent samples t test using SPSS software(version 11.5.Results: HSV type I DNA was detected in 18% of the patientsin the study group compared with 2% in the control group (Chisquare test, P = 0.008. The difference between the ranges ofintraocular pressure in the two groups was not statistically significant.Conclusion: The presence of HSV type I DNA suggests thepossible relationship between the virus and pseudoexfoliationsyndrome. It may be a treatable etiology in this multi-factorialdisorder and may help to future management of patients; especiallyto prevent some of the complications in this syndrome.

  5. Burning mouth syndrome associated with varicella zoster virus.

    Science.gov (United States)

    Nagel, Maria A; Gilden, Don

    2016-07-05

    We present two cases of burning mouth syndrome (BMS)-of 8-month duration in a 61-year-old woman and of 2-year duration in a 63-year-old woman-both associated with increased levels of antivaricella zoster virus (VZV) IgM antibodies in serum and with pain that improved with antiviral treatment. Combined with our previous finding of BMS due to herpes simplex virus type 1 (HSV-1) infection, we recommend evaluation of patients with BMS not only for VZV or HSV-1 DNA in the saliva, but also for serum anti-VZV and anti-HSV-1 IgM antibodies. Both infections are treatable with oral antiviral agents. 2016 BMJ Publishing Group Ltd.

  6. Deep insight into white spot syndrome virus vaccines: A review

    Directory of Open Access Journals (Sweden)

    MA Badhul Haq

    2012-02-01

    Full Text Available White spot syndrome virus (WSSV, the causative virus of the disease, is found in most shrimp farming areas of the world, where it causes large economic losses to the shrimp farming industry. The potentially fatal virus has been found to be a threat not only to all shrimp species, but also to other marine and freshwater crustaceans, such as crab and crayfish. To date, no effective prophylactic treatment measures are available for viral infections in shrimp and other crustaceans. Due to current aquaculture practices and the broad host range of WSSV, intervention strategies including vaccination against this virus would be pivotal to save and protect shrimp farming. Several achievements have been attained in the search of novel vaccines for WSSV. DNA vaccination, recombinant vaccines, oral vaccination techniques and gene therapy are some of the thrust areas of focus for scientists and researchers. This review article highlights the recent trends in the development of WSSV vaccines either as DNA vaccines or recombinant vaccines and their functioning strategies as suggested by the researchers worldwide.

  7. Structure of the Triatoma virus capsid.

    Science.gov (United States)

    Squires, Gaëlle; Pous, Joan; Agirre, Jon; Rozas-Dennis, Gabriela S; Costabel, Marcelo D; Marti, Gerardo A; Navaza, Jorge; Bressanelli, Stéphane; Guérin, Diego M A; Rey, Felix A

    2013-06-01

    The members of the Dicistroviridae family are non-enveloped positive-sense single-stranded RNA (+ssRNA) viruses pathogenic to beneficial arthropods as well as insect pests of medical importance. Triatoma virus (TrV), a member of this family, infects several species of triatomine insects (popularly named kissing bugs), which are vectors for human trypanosomiasis, more commonly known as Chagas disease. The potential use of dicistroviruses as biological control agents has drawn considerable attention in the past decade, and several viruses of this family have been identified, with their targets covering honey bees, aphids and field crickets, among others. Here, the crystal structure of the TrV capsid at 2.5 Å resolution is reported, showing that as expected it is very similar to that of Cricket paralysis virus (CrPV). Nevertheless, a number of distinguishing structural features support the introduction of a new genus (Triatovirus; type species TrV) under the Dicistroviridae family. The most striking differences are the absence of icosahedrally ordered VP4 within the infectious particle and the presence of prominent projections that surround the fivefold axis. Furthermore, the structure identifies a second putative autoproteolytic DDF motif in protein VP3, in addition to the conserved one in VP1 which is believed to be responsible for VP0 cleavage during capsid maturation. The potential meaning of these new findings is discussed.

  8. Porcine reproductive and respiratory syndrome virus nonstructural protein 2 (nsp2) topology and selective isoform integration in artificial membranes

    Science.gov (United States)

    Membrane modification of host subcellular compartments is critical to the replication of many RNA viruses. Enveloped viruses additionally require the ability to requisition cellular membranes during egress for the development of infectious progeny. Porcine reproductive and respiratory syndrome virus...

  9. White spot syndrome virus envelope protein VP28 is involved in the systemic infection of shrimp

    NARCIS (Netherlands)

    Hulten, van M.C.W.; Witteveldt, J.; Snippe, M.; Vlak, J.M.

    2001-01-01

    White spot syndrome virus (WSSV) is a large DNA virus infecting shrimp and other crustaceans. The virus particles contain at least five major virion proteins, of which three (VP26, VP24, and VP15) are present in the rod-shaped nucleocapsid and two (VP28 and VP19) reside in the envelope. The mode of

  10. Fitness and virulence of an ancestral White Spot Syndrome Virus isolate from shrimp

    NARCIS (Netherlands)

    Marks, H.; Duijse, J.J.A.; Zuidema, D.; Hulten, van M.C.W.; Vlak, J.M.

    2005-01-01

    White Spot Syndrome Virus, the type species of the virus family Nimaviridae, is a large dsDNA virus infecting shrimp and other crustaceans. Genomic analysis of three completely sequenced WSSV isolates identified two major polymorphic loci, ¿variable region ORF14/15¿ and ¿variable region ORF23/24¿.

  11. NSs protein of severe fever with thrombocytopenia syndrome virus suppresses interferon production through different mechanism than Rift Valley fever virus.

    Science.gov (United States)

    Zhang, S; Zheng, B; Wang, T; Li, A; Wan, J; Qu, J; Li, C H; Li, D; Liang, M

    Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly identified Phlebovirus that causes severe fever with thrombocytopenia syndrome. Our study demonstrated that SFTSV NSs functioned as IFN antagonist mainly by suppressing TBK1/IKKε-IRF3 signaling pathway. NSs interacted with and relocalized TANK-binding kinase 1 (TBK1) into NSs-induced cytoplasmic structures and this interaction could effectively inhibit downstream phosphorylation and dimerization of interferon regulatory factor 3 (IRF3), resulting in the suppression of antiviral signaling and IFN induction. Functional sites of SFTSV NSs binding with TBK1 were then studied and results showed that NSs had lost their IFN-inhibiting activity after deleting the 25 amino acids in N-terminal. Furthermore, the mechanism of Rift Valley fever virus (RVFV) NSs blocking IFN-β response were also investigated. Preliminary results showed that RVFV NSs proteins could neither interact nor co-localize with TBK1 in cytoplasm, but suppressed its expression levels, phosphorylation and dimerization of IRF3 in the subsequent steps, resulting in inhibition of the IFN-β production. Altogether, our data demonstrated the probable mechanism used by SFTSV to inhibit IFN responses which was different from RVFV and pointed toward a novel mechanism for RVFV suppressing IFN responses.

  12. Structure of the Triatoma virus capsid

    International Nuclear Information System (INIS)

    Squires, Gaëlle; Pous, Joan; Agirre, Jon; Rozas-Dennis, Gabriela S.; Costabel, Marcelo D.; Marti, Gerardo A.; Navaza, Jorge; Bressanelli, Stéphane; Guérin, Diego M. A.; Rey, Felix A.

    2013-01-01

    The crystallographic structure of TrV shows specific morphological and functional features that clearly distinguish it from the type species of the Cripavirus genus, CrPV. The members of the Dicistroviridae family are non-enveloped positive-sense single-stranded RNA (+ssRNA) viruses pathogenic to beneficial arthropods as well as insect pests of medical importance. Triatoma virus (TrV), a member of this family, infects several species of triatomine insects (popularly named kissing bugs), which are vectors for human trypanosomiasis, more commonly known as Chagas disease. The potential use of dicistroviruses as biological control agents has drawn considerable attention in the past decade, and several viruses of this family have been identified, with their targets covering honey bees, aphids and field crickets, among others. Here, the crystal structure of the TrV capsid at 2.5 Å resolution is reported, showing that as expected it is very similar to that of Cricket paralysis virus (CrPV). Nevertheless, a number of distinguishing structural features support the introduction of a new genus (Triatovirus; type species TrV) under the Dicistroviridae family. The most striking differences are the absence of icosahedrally ordered VP4 within the infectious particle and the presence of prominent projections that surround the fivefold axis. Furthermore, the structure identifies a second putative autoproteolytic DDF motif in protein VP3, in addition to the conserved one in VP1 which is believed to be responsible for VP0 cleavage during capsid maturation. The potential meaning of these new findings is discussed

  13. Structure of the Triatoma virus capsid

    Energy Technology Data Exchange (ETDEWEB)

    Squires, Gaëlle; Pous, Joan [Laboratoire de Virologie Moléculaire et Structurale, CNRS, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette CEDEX (France); Agirre, Jon [Fundación Biofísica Bizkaia, Barrio Sarriena S/N, 48940 Leioa, Bizkaia (FBB) (Spain); Unidad de Biofísica (UBF, CSIC, UPV/EHU), PO Box 644, 48080 Bilbao (Spain); Rozas-Dennis, Gabriela S. [U.N.S., San Juan 670 (8000) Bahía Blanca (Argentina); U.N.S., Avenida Alem 1253 (8000) Bahía Blanca (Argentina); Costabel, Marcelo D. [U.N.S., Avenida Alem 1253 (8000) Bahía Blanca (Argentina); Marti, Gerardo A. [Centro de Estudios Parasitológicos y de Vectores (CEPAVE-CCT, La Plata, CONICET-UNLP), Calle 2 No. 584 (1900) La Plata (Argentina); Navaza, Jorge; Bressanelli, Stéphane [Laboratoire de Virologie Moléculaire et Structurale, CNRS, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette CEDEX (France); Guérin, Diego M. A., E-mail: diego.guerin@ehu.es [Fundación Biofísica Bizkaia, Barrio Sarriena S/N, 48940 Leioa, Bizkaia (FBB) (Spain); Unidad de Biofísica (UBF, CSIC, UPV/EHU), PO Box 644, 48080 Bilbao (Spain); Rey, Felix A., E-mail: diego.guerin@ehu.es [Laboratoire de Virologie Moléculaire et Structurale, CNRS, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette CEDEX (France)

    2013-06-01

    The crystallographic structure of TrV shows specific morphological and functional features that clearly distinguish it from the type species of the Cripavirus genus, CrPV. The members of the Dicistroviridae family are non-enveloped positive-sense single-stranded RNA (+ssRNA) viruses pathogenic to beneficial arthropods as well as insect pests of medical importance. Triatoma virus (TrV), a member of this family, infects several species of triatomine insects (popularly named kissing bugs), which are vectors for human trypanosomiasis, more commonly known as Chagas disease. The potential use of dicistroviruses as biological control agents has drawn considerable attention in the past decade, and several viruses of this family have been identified, with their targets covering honey bees, aphids and field crickets, among others. Here, the crystal structure of the TrV capsid at 2.5 Å resolution is reported, showing that as expected it is very similar to that of Cricket paralysis virus (CrPV). Nevertheless, a number of distinguishing structural features support the introduction of a new genus (Triatovirus; type species TrV) under the Dicistroviridae family. The most striking differences are the absence of icosahedrally ordered VP4 within the infectious particle and the presence of prominent projections that surround the fivefold axis. Furthermore, the structure identifies a second putative autoproteolytic DDF motif in protein VP3, in addition to the conserved one in VP1 which is believed to be responsible for VP0 cleavage during capsid maturation. The potential meaning of these new findings is discussed.

  14. Immune reconstitution syndrome in a human immunodeficiency virus infected child due to giardiasis leading to shock

    Directory of Open Access Journals (Sweden)

    Sneha Nandy

    2015-01-01

    Full Text Available Human immunodeficiency virus (HIV-associated immune reconstitution inflammatory syndrome has been reported in association with tuberculosis, herpes zoster (shingles, Cryptococcus neoformans, Kaposi′s sarcoma, Pneumocystis pneumonia, hepatitis B virus, hepatitis C virus, herpes simplex virus, Histoplasma capsulatum, human papillomavirus, and Cytomegalovirus. However, it has never been documented with giardiasis. We present a 7-year-old HIV infected girl who developed diarrhea and shock following the initiation of antiretroviral therapy, and her stool showed the presence of giardiasis.

  15. Pediatric Miller Fisher Syndrome Complicating an Epstein-Barr Virus Infection.

    Science.gov (United States)

    Communal, Céline; Filleron, Anne; Baron-Joly, Sandrine; Salet, Randa; Tran, Tu-Anh

    2016-10-01

    Miller Fisher syndrome, a variant of Guillain-Barré syndrome, is an acute inflammatory demyelinating polyradiculoneuropathy that may occur weeks after a bacterial or viral infection. Campylobacter jejuni and Haemophilus influenzae are frequently reported etiological agents. We describe a boy with Miller Fisher syndrome following Epstein-002DBarr virus primary infectious mononucleosis. He presented with bilateral dysfunction of several cranial nerves and hyporeflexia of the limbs but without ataxia. Miller Fisher syndrome was confirmed by the presence of anti-GQ1b antibodies in a blood sample. Epstein-Barr virus was identified by polymerase chain reaction and serology. Epstein-Barr virus should be considered as a Miller Fisher syndrome's causative agent. The physiopathology of this condition may involve cross-reactive T-cells against Epstein-Barr virus antigens and gangliosides. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Structural brain abnormalities in Cushing's syndrome.

    Science.gov (United States)

    Bauduin, Stephanie E E C; van der Wee, Nic J A; van der Werff, Steven J A

    2018-05-08

    Alongside various physical symptoms, patients with Cushing's disease and Cushing's syndrome display a wide variety of neuropsychiatric and cognitive symptoms, which are indicative of involvement of the central nervous system. The aim of this review is to provide an overview of the structural brain abnormalities that are associated with Cushing's disease and Cushing's syndrome and their relation to behavioral and cognitive symptomatology. In this review, we discuss the gray matter structural abnormalities found in patients with active Cushing's disease and Cushing's syndrome, the reversibility and persistence of these changes and the white matter structural changes related to Cushing's syndrome. Recent findings are of particular interest because they provide more detailed information on localization of the structural changes as well as possible insights into the underlying biological processes. Active Cushing's disease and Cushing's syndrome is related to volume reductions of the hippocampus and in a prefrontal region involving the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG). Whilst there are indications that the reductions in hippocampal volume are partially reversible, the changes in the ACC and MFG appear to be more persistent. In contrast to the volumetric findings, changes in white matter connectivity are typically widespread involving multiple tracts.

  17. Cleft analysis of Zika virus non-structural protein 1

    Institute of Scientific and Technical Information of China (English)

    Somsri Wiwanitkit; Viroj Wiwanitkit

    2017-01-01

    The non-structural protein 1 is an important molecule of the viruses in flavivirus group including to Zika virus. Recently, the NS1 of Zika virus was discovered. There is still no complete information of the molecular interaction of NS1 of Zika virus which can be the clue for explanation for its pathogenesis and further drug search. Here the authors report the cleft analysis of NS1 of Zika virus and the result can be useful for future development of good diagnostic tool and antiviral drug finding for management of Zika virus.

  18. Cleft analysis of Zika virus non-structural protein 1

    Directory of Open Access Journals (Sweden)

    Somsri Wiwanitkit

    2017-08-01

    Full Text Available The non-structural protein 1 is an important molecule of the viruses in flavivirus group including to Zika virus. Recently, the NS1 of Zika virus was discovered. There is still no complete information of the molecular interaction of NS1 of Zika virus which can be the clue for explanation for its pathogenesis and further drug search. Here the authors report the cleft analysis of NS1 of Zika virus and the result can be useful for future development of good diagnostic tool and antiviral drug finding for management of Zika virus.

  19. Guillain-Barre syndrome complicating chikungunya virus infection.

    Science.gov (United States)

    Agarwal, Ayush; Vibha, Deepti; Srivastava, Achal Kumar; Shukla, Garima; Prasad, Kameshwar

    2017-06-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus which presents with symptoms of fever, rash, arthralgia, and occasional neurologic disease. While outbreaks have been earlier reported from India and other parts of the world, the recent outbreak in India witnessed more than 1000 cases. Various systemic and rarely neurological complications have been reported with CHIKV. We report two cases of Guillain-Barré syndrome (GBS) with CHIKV. GBS is a rare neurological complication which may occur after subsidence of fever and constitutional symptoms by several neurotropic viruses. We describe two cases of severe GBS which presented with rapidly progressive flaccid quadriparesis progressing to difficulty in swallowing and breathing. Both required mechanical ventilation and improved partly with plasmapharesis. The cases emphasize on (1) description of the rare complication in a setting of outbreak with CHIKV, (2) acute axonal as well as demyelinating neuropathy may occur with CHIKV, (3) accurate identification of this entity during outbreaks with dengue, both of which are vector borne and may present with similar complications.

  20. Monkey Viperin Restricts Porcine Reproductive and Respiratory Syndrome Virus Replication.

    Science.gov (United States)

    Fang, Jianyu; Wang, Haiyan; Bai, Juan; Zhang, Qiaoya; Li, Yufeng; Liu, Fei; Jiang, Ping

    2016-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen which causes huge economic damage globally in the swine industry. Current vaccination strategies provide only limited protection against PRRSV infection. Viperin is an interferon (IFN) stimulated protein that inhibits some virus infections via IFN-dependent or IFN-independent pathways. However, the role of viperin in PRRSV infection is not well understood. In this study, we cloned the full-length monkey viperin (mViperin) complementary DNA (cDNA) from IFN-α-treated African green monkey Marc-145 cells. It was found that the mViperin is up-regulated following PRRSV infection in Marc-145 cells along with elevated IRF-1 gene levels. IFN-α induced mViperin expression in a dose- and time-dependent manner and strongly inhibits PRRSV replication in Marc-145 cells. Overexpression of mViperin suppresses PRRSV replication by blocking the early steps of PRRSV entry and genome replication and translation but not inhibiting assembly and release. And mViperin co-localized with PRRSV GP5 and N protein, but only interacted with N protein in distinct cytoplasmic loci. Furthermore, it was found that the 13-16 amino acids of mViperin were essential for inhibiting PRRSV replication, by disrupting the distribution of mViperin protein from the granular distribution to a homogeneous distribution in the cytoplasm. These results could be helpful in the future development of novel antiviral therapies against PRRSV infection.

  1. Small round structured viruses (SRSVs) and transmission electron ...

    African Journals Online (AJOL)

    Administrator

    immune-electron microscopy (IEM) from patients' feces. They reported this virus particle as the causative agent of winter vomiting outbreaks in Norwalk (Kapikian et al.,. 1972). This is the remarkable landmark study of non- bacterial gastroenteritis viruses, especially for small round structured viruses (SRSVs). After that, many.

  2. Antiviral property of marine actinomycetes against white spot syndrome virus in penaeid shrimps

    Digital Repository Service at National Institute of Oceanography (India)

    Kumar, S.S.; Philip, R.; Achuthankutty, C.T.

    Aquaculture farms, particularly in Southeast Asia are facing severe crisis due to increasing incidences of White Spot Syndrome Virus (WSSV). Actinomycetes have provided many important bioactive compounds of high prophylactic and therapeutic value...

  3. FASEB Science Research Conference on Virus Structure and Assembly

    Science.gov (United States)

    2017-10-24

    Report: FASEB Science Research Conference on Virus Structure and Assembly The views, opinions and/or findings contained in this report are those of the...Title: FASEB Science Research Conference on Virus Structure and Assembly Report Term: 0-Other Email: srcgrants@faseb.org Distribution Statement...support for the 2016 FASEB Science Research Conference on Virus Structure and Assembly which was held July 24-29, 2016 in Steamboat Springs, CO. This

  4. Structural Pituitary Abnormalities Associated With CHARGE Syndrome

    Science.gov (United States)

    Gregory, Louise C.; Gevers, Evelien F.; Baker, Joanne; Kasia, Tessa; Chong, Kling; Josifova, Dragana J.; Caimari, Maria; Bilan, Frederic; McCabe, Mark J.

    2013-01-01

    Introduction: CHARGE syndrome is a multisystem disorder that, in addition to Kallmann syndrome/isolated hypogonadotrophic hypogonadism, has been associated with anterior pituitary hypoplasia (APH). However, structural abnormalities such as an ectopic posterior pituitary (EPP) have not yet been described in such patients. Objective: The aims of the study were: 1) to describe the association between CHARGE syndrome and a structurally abnormal pituitary gland; and 2) to investigate whether CHD7 variants, which are identified in 65% of CHARGE patients, are common in septo-optic dysplasia /hypopituitarism. Methods: We describe 2 patients with features of CHARGE and EPP. CHD7 was sequenced in these and other patients with septo-optic dysplasia/hypopituitarism. Results: EPP, APH, and GH, TSH, and probable LH/FSH deficiency were present in 1 patient, and EPP and APH with GH, TSH, LH/FSH, and ACTH deficiency were present in another patient, both of whom had features of CHARGE syndrome. Both had variations in CHD7 that were novel and undetected in control cohorts or in the international database of CHARGE patients, but were also present in their unaffected mothers. No CHD7 variants were detected in the patients with septo-optic dysplasia/hypopituitarism without additional CHARGE features. Conclusion: We report a novel association between CHARGE syndrome and structural abnormalities of the pituitary gland in 2 patients with variations in CHD7 that are of unknown significance. However, CHD7 mutations are an uncommon cause of septo-optic dysplasia or hypopituitarism. Our data suggest the need for evaluation of pituitary function/anatomy in patients with CHARGE syndrome. PMID:23526466

  5. Two White Spot Syndrome Virus MicroRNAs Target the Dorsal Gene To Promote Virus Infection in Marsupenaeus japonicus Shrimp.

    Science.gov (United States)

    Ren, Qian; Huang, Xin; Cui, Yalei; Sun, Jiejie; Wang, Wen; Zhang, Xiaobo

    2017-04-15

    In eukaryotes, microRNAs (miRNAs) serve as regulators of many biological processes, including virus infection. An miRNA can generally target diverse genes during virus-host interactions. However, the regulation of gene expression by multiple miRNAs has not yet been extensively explored during virus infection. This study found that the Spaztle (Spz)-Toll-Dorsal-antilipopolysaccharide factor (ALF) signaling pathway plays a very important role in antiviral immunity against invasion of white spot syndrome virus (WSSV) in shrimp ( Marsupenaeus japonicus ). Dorsal , the central gene in the Toll pathway, was targeted by two viral miRNAs (WSSV-miR-N13 and WSSV-miR-N23) during WSSV infection. The regulation of Dorsal expression by viral miRNAs suppressed the Spz-Toll-Dorsal-ALF signaling pathway in shrimp in vivo , leading to virus infection. Our study contributes novel insights into the viral miRNA-mediated Toll signaling pathway during the virus-host interaction. IMPORTANCE An miRNA can target diverse genes during virus-host interactions. However, the regulation of gene expression by multiple miRNAs during virus infection has not yet been extensively explored. The results of this study indicated that the shrimp Dorsal gene, the central gene in the Toll pathway, was targeted by two viral miRNAs during infection with white spot syndrome virus. Regulation of Dorsal expression by viral miRNAs suppressed the Spz-Toll-Dorsal-ALF signaling pathway in shrimp in vivo , leading to virus infection. Our study provides new insight into the viral miRNA-mediated Toll signaling pathway in virus-host interactions. Copyright © 2017 American Society for Microbiology.

  6. Safety and protective efficacy of porcine reproductive and respiratory syndrome recombinant virus vaccines in young pigs.

    NARCIS (Netherlands)

    Verheije, M.H.; Kroese, M.V.; Linden, van der I.F.A.; Boer-Luijtze, de E.A.; Rijn, van P.A.; Pol, J.M.A.; Meulenberg, J.J.M.; Steverink, P.J.G.M.

    2003-01-01

    Three porcine reproductive and respiratory syndrome virus (PRRSV) recombinants, generated by mutagenesis of an infectious cDNA clone of the Lelystad virus (LV) isolate, were tested for their safety and protective efficacy as potential PRRSV vaccines in pigs. Recombinant vABV688 contains two amino

  7. Protection of Penaeus monodon against White Spot Syndrome Virus by oral vaccination

    NARCIS (Netherlands)

    Witteveldt, J.; Cifuentes, C.; Vlak, J.M.; Hulten, van M.C.W.

    2004-01-01

    White spot syndrome virus (WSSV) occurs worldwide and causes high mortality and considerable economic damage to the shrimp farming industry. No adequate treatments against this virus are available. It is generally accepted that invertebrates such as shrimp do not have an adaptive immune response

  8. Virion composition and genomics of white spot syndrome virus of shrimp

    NARCIS (Netherlands)

    Hulten, van M.C.W.

    2001-01-01


    Since its first discovery in Taiwan in 1992, White spot syndrome virus (WSSV) has caused major economic damage to shrimp culture. The virus has spread rapidly through Asia and reached the Western Hemisphere in 1995 (Texas), where it continued its devastating effect

  9. Evolutionary and molecular analysis of the emergent severe fever with thrombocytopenia syndrome virus.

    Science.gov (United States)

    Lam, Tommy Tsan-Yuk; Liu, Wei; Bowden, Thomas A; Cui, Ning; Zhuang, Lu; Liu, Kun; Zhang, Yao-Yun; Cao, Wu-Chun; Pybus, Oliver G

    2013-03-01

    In 2009, a novel Bunyavirus, called severe fever with thrombocytopenia syndrome virus (SFTSV) was identified in the vicinity of Huaiyangshan, China. Clinical symptoms of this zoonotic virus included severe fever, thrombocytopenia, and leukocytopenia, with a mortality rate of ~10%. By the end of 2011 the disease associated with this pathogen had been reported from eleven Chinese provinces and human-to-human transmission suspected. However, current understanding of the evolution and molecular epidemiology of SFTSV before and after its identification is limited. To address this we undertake phylogenetic, evolutionary and structural analyses of all available SFTSV genetic sequences, including a new SFTSV complete genome isolated from a patient from Henan in 2011. Our discovery of a mosaic L segment sequence, which is descended from two major circulating lineages of SFTSV in China, represents the first evidence that homologous recombination plays a role in SFTSV evolution. Selection analyses indicate that negative selection is predominant in SFTSV genes, yet differences in selective forces among genes are consistent between Phlebovirus species. Further analysis reveals structural conservation between SFTSV and Rift Valley fever virus in the residues of their nucleocapsids that are responsible for oligomerisation and RNA-binding, suggesting the viruses share similar modes of higher-order assembly. We reconstruct the epidemic history of SFTSV using molecular clock and coalescent-based methods, revealing that the extant SFTSV lineages originated 50-150 years ago, and that the viral population experienced a recent growth phase that concurs with and extends the earliest serological reports of SFTSV infection. Taken together, our combined structural and phylogenetic analyses shed light into the evolutionary behaviour of SFTSV in the context of other, better-known, pathogenic Phleboviruses. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Characterization and interactome study of white spot syndrome virus envelope protein VP11.

    Directory of Open Access Journals (Sweden)

    Wang-Jing Liu

    Full Text Available White spot syndrome virus (WSSV is a large enveloped virus. The WSSV viral particle consists of three structural layers that surround its core DNA: an outer envelope, a tegument and a nucleocapsid. Here we characterize the WSSV structural protein VP11 (WSSV394, GenBank accession number AF440570, and use an interactome approach to analyze the possible associations between this protein and an array of other WSSV and host proteins. Temporal transcription analysis showed that vp11 is an early gene. Western blot hybridization of the intact viral particles and fractionation of the viral components, and immunoelectron microscopy showed that VP11 is an envelope protein. Membrane topology software predicted VP11 to be a type of transmembrane protein with a highly hydrophobic transmembrane domain at its N-terminal. Based on an immunofluorescence assay performed on VP11-transfected Sf9 cells and a trypsin digestion analysis of the virion, we conclude that, contrary to topology software prediction, the C-terminal of this protein is in fact inside the virion. Yeast two-hybrid screening combined with co-immunoprecipitation assays found that VP11 directly interacted with at least 12 other WSSV structural proteins as well as itself. An oligomerization assay further showed that VP11 could form dimers. VP11 is also the first reported WSSV structural protein to interact with the major nucleocapsid protein VP664.

  11. Structural organization of DNA in chlorella viruses.

    Directory of Open Access Journals (Sweden)

    Timo Wulfmeyer

    Full Text Available Chlorella viruses have icosahedral capsids with an internal membrane enclosing their large dsDNA genomes and associated proteins. Their genomes are packaged in the particles with a predicted DNA density of ca. 0.2 bp nm(-3. Occasionally infection of an algal cell by an individual particle fails and the viral DNA is dynamically ejected from the capsid. This shows that the release of the DNA generates a force, which can aid in the transfer of the genome into the host in a successful infection. Imaging of ejected viral DNA indicates that it is intimately associated with proteins in a periodic fashion. The bulk of the protein particles detected by atomic force microscopy have a size of ∼60 kDa and two proteins (A278L and A282L of about this size are among 6 basic putative DNA binding proteins found in a proteomic analysis of DNA binding proteins packaged in the virion. A combination of fluorescence images of ejected DNA and a bioinformatics analysis of the DNA reveal periodic patterns in the viral DNA. The periodic distribution of GC rich regions in the genome provides potential binding sites for basic proteins. This DNA/protein aggregation could be responsible for the periodic concentration of fluorescently labeled DNA observed in ejected viral DNA. Collectively the data indicate that the large chlorella viruses have a DNA packaging strategy that differs from bacteriophages; it involves proteins and share similarities to that of chromatin structure in eukaryotes.

  12. Cleft analysis of Zika virus non-structural protein 1

    OpenAIRE

    Somsri Wiwanitkit; Viroj Wiwanitkit

    2017-01-01

    The non-structural protein 1 is an important molecule of the viruses in flavivirus group including to Zika virus. Recently, the NS1 of Zika virus was discovered. There is still no complete information of the molecular interaction of NS1 of Zika virus which can be the clue for explanation for its pathogenesis and further drug search. Here the authors report the cleft analysis of NS1 of Zika virus and the result can be useful for future development of good diagnostic tool and antiviral drug fin...

  13. Scavenger Receptor C Mediates Phagocytosis of White Spot Syndrome Virus and Restricts Virus Proliferation in Shrimp

    Science.gov (United States)

    Yang, Ming-Chong; Shi, Xiu-Zhen; Yang, Hui-Ting; Sun, Jie-Jie; Xu, Ling; Wang, Xian-Wei; Zhao, Xiao-Fan

    2016-01-01

    Scavenger receptors are an important class of pattern recognition receptors that play several important roles in host defense against pathogens. The class C scavenger receptors (SRCs) have only been identified in a few invertebrates, and their role in the immune response against viruses is seldom studied. In this study, we firstly identified an SRC from kuruma shrimp, Marsupenaeus japonicus, designated MjSRC, which was significantly upregulated after white spot syndrome virus (WSSV) challenge at the mRNA and protein levels in hemocytes. The quantity of WSSV increased in shrimp after knockdown of MjSRC, compared with the controls. Furthermore, overexpression of MjSRC led to enhanced WSSV elimination via phagocytosis by hemocytes. Pull-down and co-immunoprecipitation assays demonstrated the interaction between MjSRC and the WSSV envelope protein. Electron microscopy observation indicated that the colloidal gold-labeled extracellular domain of MjSRC was located on the outer surface of WSSV. MjSRC formed a trimer and was internalized into the cytoplasm after WSSV challenge, and the internalization was strongly inhibited after knockdown of Mjβ-arrestin2. Further studies found that Mjβ-arrestin2 interacted with the intracellular domain of MjSRC and induced the internalization of WSSV in a clathrin-dependent manner. WSSV were co-localized with lysosomes in hemocytes and the WSSV quantity in shrimp increased after injection of lysosome inhibitor, chloroquine. Collectively, this study demonstrated that MjSRC recognized WSSV via its extracellular domain and invoked hemocyte phagocytosis to restrict WSSV systemic infection. This is the first study to report an SRC as a pattern recognition receptor promoting phagocytosis of a virus. PMID:28027319

  14. Middle east respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus ankara efficiently induces virus-neutralizing antibodies

    NARCIS (Netherlands)

    F. Song (Fei); R. Fux (Robert); L.B.V. Provacia (Lisette); A. Volz (Asisa); M. Eickmann; S. Becker (Stephan); A.D.M.E. Osterhaus (Albert); B.L. Haagmans (Bart); G. Suttera (Gerd)

    2013-01-01

    textabstractMiddle East respiratory syndrome coronavirus (MERS-CoV) has recently emerged as a causative agent of severe respiratory disease in humans. Here, we constructed recombinant modified vaccinia virus Ankara (MVA) expressing full-length MERS-CoV spike (S) protein (MVA-MERS-S). The genetic

  15. Evaluation of white spot syndrome virus variable DNA loci as molecular markers of virus spread at intermediate spatiotemporal scales

    NARCIS (Netherlands)

    Bui Thi Minh Dieu,; Marks, H.; Zwart, M.P.; Vlak, J.M.

    2010-01-01

    Variable genomic loci have been employed in a number of molecular epidemiology studies of white spot syndrome virus (WSSV), but it is unknown which loci are suitable molecular markers for determining WSSV spread on different spatiotemporal scales. Although previous work suggests that multiple

  16. Solution structures of potato virus X and narcissus mosaic virus from Raman optical activity

    DEFF Research Database (Denmark)

    Blanch, Ewan W.; Robinson, David J.; Hecht, Lutz

    2002-01-01

    Potato virus X (PVX) and narcissus mosaic virus (NMV) were studied using vibrational Raman optical activity (ROA) in order to obtain new information on the structures of their coat protein subunits. The ROA spectra of the two intact virions are very similar to each other and similar to that of to......Potato virus X (PVX) and narcissus mosaic virus (NMV) were studied using vibrational Raman optical activity (ROA) in order to obtain new information on the structures of their coat protein subunits. The ROA spectra of the two intact virions are very similar to each other and similar...

  17. Molecular structures of viruses from Raman optical activity

    DEFF Research Database (Denmark)

    Blanch, Ewan W.; Hecht, Lutz; Syme, Christopher D.

    2002-01-01

    A vibrational Raman optical activity (ROA) study of a range of different structural types of virus exemplified by filamentous bacteriophage fd, tobacco mosaic virus, satellite tobacco mosaic virus, bacteriophage MS2 and cowpea mosaic virus has revealed that, on account of its sensitivity to chira......A vibrational Raman optical activity (ROA) study of a range of different structural types of virus exemplified by filamentous bacteriophage fd, tobacco mosaic virus, satellite tobacco mosaic virus, bacteriophage MS2 and cowpea mosaic virus has revealed that, on account of its sensitivity...... (top component) of cowpea mosaic virus from those of the intact middle and bottom-upper components separated by means of a caesium chloride density gradient, the ROA spectrum of the viral RNA was obtained, which revealed that the RNA takes up an A-type single-stranded helical conformation...... and that the RNA conformations in the middle and bottom-upper components are very similar. This information is not available from the X-ray crystal structure of cowpea mosaic virus since no nucleic acid is visible....

  18. Reversion of a live porcine reproductive and respiratory syndrome virus vaccine investigated by parallel mutations

    DEFF Research Database (Denmark)

    Nielsen, Henriette S.; Oleksiewicz, M.B.; Forsberg, R.

    2001-01-01

    A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates was sequen......A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates...... in the vaccine virus sequence during cell-culture adaptation. Evaluation of the remaining mutations in the ORF1 sequence revealed stronger selective pressure for amino acid conservation during spread in pigs than during vaccine production. Furthermore, it was found that the selective pressure did not change...

  19. Quasispecies variation of porcine reproductive and respiratory syndrome virus during natural infection

    International Nuclear Information System (INIS)

    Goldberg, Tony L.; Lowe, James F.; Milburn, Suzanne M.; Firkins, Lawrence D.

    2003-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) displays notorious genetic, antigenic, and clinical variability. Little is known, however, about the nature and extent of viral variation present within naturally infected animals. By amplifying and cloning the open reading frame 5 gene from tonsils of naturally infected swine, and by sequencing individual clones, we characterized viral diversity in nine animals from two farms. All animals harbored multiple PRRSV variants at both the nucleic and the amino acid levels. Structural variation and rates of synonymous and nonsynonymous nucleotide substitution were no different within known epitopes than elsewhere. Analysis of molecular variance indicated that differences between farms, among animals within farms, and within individual animals accounted for 92.94, 3.84, and 3.22% of the total viral genetic variability observed, respectively. PRRSV exists during natural infection as a quasispecies distribution of related genotypes. Positive natural selection for immune evasiveness does not appear to maintain this diversity

  20. Characterization of ORF89 - A latency-related gene of white spot syndrome virus

    International Nuclear Information System (INIS)

    Hossain, M.S.; Khadijah, Siti; Kwang, Jimmy

    2004-01-01

    Open reading frame 89 (ORF89) is one of the three genes that are believed to be involved in the latent infection of white spot syndrome virus (WSSV). Here, we report the structure and functional characterization of ORF89. cDNA sequencing, 5' RLM-RACE, and 3' RLM-RACE showed that ORF89 gene is transcribed into an unspliced mRNA of 4436 nucleotides, which is predicted to encode a protein of 1437 amino acids. ORF89 expressed an approximately 165-kDa protein in Sf9 cells that localized in the nucleus. Amino acids 678-683 were found to be essential for nuclear localization. Cotransfection assays demonstrated that ORF89 protein repressed its own promoter as well as those of a protein kinase and the thymidine-thymidylate kinase genes of WSSV. SYBR Green real-time PCR indicated that the repression occurred at the transcriptional level

  1. Radioimmunoassay and enzyme-linked immunoassay of antibodies to the core protein (P24) of human T-lymphotropic virus (HTLV III). [Acquired immunodeficiency syndrome (AIDS)

    Energy Technology Data Exchange (ETDEWEB)

    Neurath, A R; Strick, N; Sproul, P

    1985-05-01

    Human T-cell lymphotropic viruses designated HTLV III or LAV are considered to represent the causative agents of the acquired immunodeficiency syndrome (AIDS). Therefore a simple direct RIA or ELISA method for antibodies to distinct epitopes of HTLV III/LAV structural components would be of great value. The authors describe RIA and ELISA assays which obviate the need for purified virus or virus proteins, do not utilize infected cells and thus do not diminish the source for continuous production of viral antigens and are specific for a major core protein of HTLV III/LAV.

  2. Mortality Due to Porcine Reproductive and Respiratory Syndrome Virus in Immunocompromised G?ttingen Minipigs (Sus scrofa domestica)

    OpenAIRE

    Pils, Marina C; Dreckmann, Karla; Jansson, Katharina; Glage, Silke; Held, Nadine; Sommer, Wiebke; L?nger, Florian; Avsar, Murat; Warnecke, Gregor; Bleich, Andr?

    2016-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) infection was diagnosed in 6 G?ttingen minipigs (Sus scrofa domestica) with severe interstitial pneumonia. The virus was defined as a North American (NA) subtype virus, which is common in the commercial pig population and might be derived from a widely used attenuated live-virus vaccine in Europe. The ORF5 sequence of the isolated PRRSV was 98% identical to the vaccine virus. The affected pigs were part of a lung transplantation mode...

  3. Duck egg-drop syndrome caused by BYD virus, a new Tembusu-related flavivirus.

    Directory of Open Access Journals (Sweden)

    Jingliang Su

    Full Text Available Since April 2010, a severe outbreak of duck viral infection, with egg drop, feed uptake decline and ovary-oviduct disease, has spread around the major duck-producing regions in China. A new virus, named BYD virus, was isolated in different areas, and a similar disease was reproduced in healthy egg-producing ducks, infecting with the isolated virus. The virus was re-isolated from the affected ducks and replicated well in primary duck embryo fibroblasts and Vero cells, causing the cytopathic effect. The virus was identified as an enveloped positive-stranded RNA virus with a size of approximately 55 nm in diameter. Genomic sequencing of the isolated virus revealed that it is closely related to Tembusu virus (a mosquito-borne Ntaya group flavivirus, with 87-91% nucleotide identity of the partial E (envelope proteins to that of Tembusu virus and 72% of the entire genome coding sequence with Bagaza virus, the most closely related flavivirus with an entirely sequenced genome. Collectively our systematic studies fulfill Koch's postulates, and therefore, the causative agent of the duck egg drop syndrome occurring in China is a new flavivirus. Flavivirus is an emerging and re-emerging zoonotic pathogen and BYD virus that causes severe egg-drop, could be disastrous for the duck industry. More importantly its public health concerns should also be evaluated, and its epidemiology should be closely watched due to the zoonotic nature of flaviviruses.

  4. Metabolic syndrome in human immunodeficiency virus positive patients

    Directory of Open Access Journals (Sweden)

    Sarita Bajaj

    2013-01-01

    Full Text Available Aims and Objectives : To assess the prevalence of metabolic syndrome (MetS in human immunodeficiency virus (HIV positive patients. Prevalence of MetS was compared in patients who were not on highly active antiretroviral therapy (HAART to patients who were on HAART. Materials and Methods: Seventy HIV positive cases were studied. Pregnant and lactating women, patients on drugs other than HAART known to cause metabolic abnormalities and those having diabetes or hypertension were excluded. Cases were evaluated for MetS by using National Cholesterol Education Program Adult Treatment Panel-III. Results: 47 cases were on HAART and 23 cases were not on HAART. Fasting Blood Glucose ≥100 mg/dl was present in 28.6% cases, out of whom 27.7% were on HAART and 30.4% were not on HAART (P = 0.8089. 12.9% cases had BP ≥130/≥85 mm Hg, out of whom 14.9% were on HAART and 8.7% were not on HAART (P = 0.4666. 42.9% cases had TG ≥150 mg/dl, out of whom 44.7% were on HAART and 39.1% were not on HAART (P = 0.6894. HDL cholesterol was low (males <40 mg/dl, females <50 mg/dl in 50% cases, out of whom 55.3% were on HAART and 39.1% were not on HAART (P = 0.2035. Conclusions: Prevalence of MetS was 20%. Majority of patients had only one component of MetS (32.9%. Low HDL was present in 50%, followed by raised triglycerides in 42.9%. Waist circumference was not increased in any of the patients. There was no statistically significant difference between those on HAART and those not on HAART in distribution of risk factors and individual components of MetS.

  5. Suppression of Shrimp Melanization during White Spot Syndrome Virus Infection*

    Science.gov (United States)

    Sutthangkul, Jantiwan; Amparyup, Piti; Charoensapsri, Walaiporn; Senapin, Saengchan; Phiwsaiya, Kornsunee; Tassanakajon, Anchalee

    2015-01-01

    The melanization cascade, activated by the prophenoloxidase (proPO) system, plays a key role in the production of cytotoxic intermediates, as well as melanin products for microbial sequestration in invertebrates. Here, we show that the proPO system is an important component of the Penaeus monodon shrimp immune defense toward a major viral pathogen, white spot syndrome virus (WSSV). Gene silencing of PmproPO(s) resulted in increased cumulative shrimp mortality after WSSV infection, whereas incubation of WSSV with an in vitro melanization reaction prior to injection into shrimp significantly increased the shrimp survival rate. The hemolymph phenoloxidase (PO) activity of WSSV-infected shrimp was extremely reduced at days 2 and 3 post-injection compared with uninfected shrimp but was fully restored after the addition of exogenous trypsin, suggesting that WSSV probably inhibits the activity of some proteinases in the proPO cascade. Using yeast two-hybrid screening and co-immunoprecipitation assays, the viral protein WSSV453 was found to interact with the proPO-activating enzyme 2 (PmPPAE2) of P. monodon. Gene silencing of WSSV453 showed a significant increase of PO activity in WSSV-infected shrimp, whereas co-silencing of WSSV453 and PmPPAE2 did not, suggesting that silencing of WSSV453 partially restored the PO activity via PmPPAE2 in WSSV-infected shrimp. Moreover, the activation of PO activity in shrimp plasma by PmPPAE2 was significantly decreased by preincubation with recombinant WSSV453. These results suggest that the inhibition of the shrimp proPO system by WSSV partly occurs via the PmPPAE2-inhibiting activity of WSSV453. PMID:25572398

  6. Suppression of shrimp melanization during white spot syndrome virus infection.

    Science.gov (United States)

    Sutthangkul, Jantiwan; Amparyup, Piti; Charoensapsri, Walaiporn; Senapin, Saengchan; Phiwsaiya, Kornsunee; Tassanakajon, Anchalee

    2015-03-06

    The melanization cascade, activated by the prophenoloxidase (proPO) system, plays a key role in the production of cytotoxic intermediates, as well as melanin products for microbial sequestration in invertebrates. Here, we show that the proPO system is an important component of the Penaeus monodon shrimp immune defense toward a major viral pathogen, white spot syndrome virus (WSSV). Gene silencing of PmproPO(s) resulted in increased cumulative shrimp mortality after WSSV infection, whereas incubation of WSSV with an in vitro melanization reaction prior to injection into shrimp significantly increased the shrimp survival rate. The hemolymph phenoloxidase (PO) activity of WSSV-infected shrimp was extremely reduced at days 2 and 3 post-injection compared with uninfected shrimp but was fully restored after the addition of exogenous trypsin, suggesting that WSSV probably inhibits the activity of some proteinases in the proPO cascade. Using yeast two-hybrid screening and co-immunoprecipitation assays, the viral protein WSSV453 was found to interact with the proPO-activating enzyme 2 (PmPPAE2) of P. monodon. Gene silencing of WSSV453 showed a significant increase of PO activity in WSSV-infected shrimp, whereas co-silencing of WSSV453 and PmPPAE2 did not, suggesting that silencing of WSSV453 partially restored the PO activity via PmPPAE2 in WSSV-infected shrimp. Moreover, the activation of PO activity in shrimp plasma by PmPPAE2 was significantly decreased by preincubation with recombinant WSSV453. These results suggest that the inhibition of the shrimp proPO system by WSSV partly occurs via the PmPPAE2-inhibiting activity of WSSV453. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Structural protein relationships among eastern equine encephalitis viruses.

    Science.gov (United States)

    Strizki, J M; Repik, P M

    1994-11-01

    We have re-evaluated the relationships among the polypeptides of eastern equine encephalitis (EEE) viruses using SDS-PAGE and peptide mapping of individual virion proteins. Four to five distinct polypeptide bands were detected upon SDS-PAGE analysis of viruses: the E1, E2 and C proteins normally associated with alphavirus virions, as well as an additional more rapidly-migrating E2-associated protein and a high M(r) (HMW) protein. In contrast with previous findings by others, the electrophoretic profiles of the virion proteins of EEE viruses displayed a marked correlation with serotype. The protein profiles of the 33 North American (NA)-serotype viruses examined were remarkably homogeneous, with variation detected only in the E1 protein of two isolates. In contrast, considerable heterogeneity was observed in the migration profiles of both the E1 and E2 glycoproteins of the 13 South American (SA)-type viruses examined. Peptide mapping of individual virion proteins using limited proteolysis with Staphylococcus aureus V8 protease confirmed that, in addition to the homogeneity evident among NA-type viruses and relative heterogeneity among SA-type viruses, the E1 and E2 proteins of NA- and SA-serotype viruses exhibited serotype-specific structural variation. The C protein was highly conserved among isolates of both virus serotypes. Endoglycosidase analyses of intact virions did not reveal substantial glycosylation differences between the glycoproteins of NA- and SA-serotype viruses. Both the HMW protein and the E2 protein (doublet) of EEE virus appeared to contain, at least in part, high-mannose type N-linked oligosaccharides. No evidence of O-linked glycans was found on either the E1 or the E2 glycoprotein. Despite the observed structural differences between proteins of NA- and SA-type viruses, Western blot analyses utilizing polyclonal antibodies indicated that immunoreactive epitopes appeared to be conserved.

  8. Evolutionary and molecular analysis of the emergent severe fever with thrombocytopenia syndrome virus

    OpenAIRE

    Lam, Tommy Tsan-Yuk; Liu, Wei; Bowden, Thomas A.; Cui, Ning; Zhuang, Lu; Liu, Kun; Zhang, Yao-Yun; Cao, Wu-Chun; Pybus, Oliver G.

    2013-01-01

    In 2009, a novel Bunyavirus, called severe fever with thrombocytopenia syndrome virus (SFTSV) was identified in the vicinity of Huaiyangshan, China. Clinical symptoms of this zoonotic virus included severe fever, thrombocytopenia, and leukocytopenia, with a mortality rate of ?10%. By the end of 2011 the disease associated with this pathogen had been reported from eleven Chinese provinces and human-to-human transmission suspected. However, current understanding of the evolution and molecular e...

  9. Drug-induced hypersensitivity syndrome associated with Epstein-Barr virus infection.

    Science.gov (United States)

    Descamps, V; Mahe, E; Houhou, N; Abramowitz, L; Rozenberg, F; Ranger-Rogez, S; Crickx, B

    2003-05-01

    Association of drug-induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV-6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant-induced hypersensitivity syndrome. We report a case of severe allopurinol-induced hypersensitivity syndrome with pancreatitis associated with Epstein-Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti-EBV early antigen (EA) IgM antibodies and an increase in anti-EBV EA IgG antibodies, whereas no anti-EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV-6 was suggested only by the presence of anti-HHV-6 IgM antibodies, but HHV-6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV-6 or CMV, in the development of drug-induced hypersensitivity syndrome.

  10. Horizontal transmission dynamics of White spot syndrome virus by cohabitation trials in juvenile Penaeus monodon and P. vannamei

    NARCIS (Netherlands)

    Ngo Xuan, T.; Verreth, J.A.J.; Vlak, J.M.; Jong, de M.C.M.

    2014-01-01

    White spot syndrome virus (WSSV), a rod-shaped double-stranded DNA virus, is an infectious agent causing fatal disease in shrimp farming around the globe. Within shrimp populations WSSV is transmitted very fast, however, the modes and dynamics of transmission of this virus are not well understood.

  11. Emergence of Epidemic Zika Virus Transmission and Congenital Zika Syndrome: Are Recently Evolved Traits to Blame?

    OpenAIRE

    Scott C. Weaver

    2017-01-01

    ABSTRACT The mechanisms responsible for the dramatic emergence of Zika virus (ZIKV), accompanied by congenital Zika syndrome and Guillain-Barr? syndrome (GBS), remain unclear. However, two hypotheses are prominent: (i) evolution for enhanced urban transmission via adaptation to mosquito vectors, or for enhanced human infection to increase amplification, or (ii) the stochastic introduction of ZIKV into large, naive human populations in regions with abundant Aedes aegypti populations, leading t...

  12. Curcumin is a promising inhibitor of genotype 2 porcine reproductive and respiratory syndrome virus infection.

    Science.gov (United States)

    Du, Taofeng; Shi, Yunpeng; Xiao, Shuqi; Li, Na; Zhao, Qin; Zhang, Angke; Nan, Yuchen; Mu, Yang; Sun, Yani; Wu, Chunyan; Zhang, Hongtao; Zhou, En-Min

    2017-10-10

    Porcine reproductive and respiratory syndrome virus (PRRSV) could lead to pandemic diseases and huge financial losses to the swine industry worldwide. Curcumin, a natural compound, has been reported to serve as an entry inhibitor of hepatitis C virus, chikungunya virus and vesicular stomatitis virus. In this study, we investigated the potential effect of curcumin on early stages of PRRSV infection. Curcumin inhibited infection of Marc-145 cells and porcine alveolar macrophages (PAMs) by four different genotype 2 PRRSV strains, but had no effect on the levels of major PRRSV receptor proteins on Marc-145 cells and PAMs or on PRRSV binding to Marc-145 cells. However, curcumin did block two steps of the PRRSV infection process: virus internalization and virus-mediated cell fusion. Our results suggested that an inhibition of genotype 2 PRRSV infection by curcumin is virus strain-independent, and mainly inhibited by virus internalization and cell fusion mediated by virus. Collectively, these results demonstrate that curcumin holds promise as a new anti-PRRSV drug.

  13. Hepatopulmonary syndrome in a patient with AIDS and virus C cirrhosis (viral cirrhosis type C)

    International Nuclear Information System (INIS)

    Ferreira, Maria Angelica; Gazzana, Marcelo Basso; Barreto, Sergio Saldanha Menna; Knorst, Marli Maria

    2001-01-01

    Hepatopulmonary syndrome is characterized by a triad consisting of liver disorder, pulmonary vascular dilatation, and hypoxaemia. No case of hepatopulmonary syndrome associated with AIDS has been reported so far. In this study, the authors report the case of a 43-year woman with AIDS and virus C cirrhosis taking prophylactic cotrimoxazole for pneumocystosis and retroviral therapy. Upon admission, the patient presented dyspnoea, cyanosis, digital clubbing, vascular spiders, and normal chest examination. Chest X-ray revealed bilateral interstitial infiltration and evidenced increased alveolar-arterial gradient and liver function impairment. Intrapulmonary shunt was evidenced by contrast-enhanced echocardiography and radionuclide perfusion scanning, thus confirming hepatopulmonary syndrome. (author)

  14. Antibodies against Severe Fever with Thrombocytopenia Syndrome Virus in Healthy Persons, China, 2013

    Science.gov (United States)

    Zhang, Lei; Sun, Jimin; Yan, Jie; Lv, Huakun; Chai, Chengliang; Sun, Yi; Shao, Bin; Jiang, Jianmin; Chen, Zhiping

    2014-01-01

    In June 2013, a subclinical infection with severe fever with thrombocytopenia syndrome virus (SFTSV) was detected in Zhejiang Province, China, prompting seroprevalence studies in 6 districts within the province. Of 986 healthy persons tested, 71 had IgG antibodies against SFTSV. This finding suggests that most natural infections with SFTSV are mild or subclinical. PMID:25061813

  15. Zika virus infection and Guillain-Barré syndrome in three patients from Suriname

    NARCIS (Netherlands)

    T. Langerak (Thomas); Yang, H. (Harvey); Baptista, M. (Mark); Doornekamp, L. (Laura); Kerkman, T. (Tessa); Codrington, J. (John); Roosblad, J. (Jimmy); Vreden, S.G.S. (Stephen G.S.); E.I. de Bruin (Esther); R. Mögling (Ramona); B.C. Jacobs (Bart); S.D. Pas (Suzan); C.H. Geurts van Kessel (Corine); C.B.E.M. Reusken (Chantal); M.P.G. Koopmans D.V.M. (Marion); E.C.M. van Gorp (Eric); Alberga, H. (Henk)

    2016-01-01

    textabstractWe present three patients from Suriname who were diagnosed with Guillain-Barré syndrome (GBS) during the Zika virus (ZIKV) outbreak in this country. One patient had a positive ZIKV urine real-time RT-PCR (qRT-PCR) result. The other two patients had a negative ZIKV urine qRT-PCR but a

  16. Antibodies against severe fever with Thrombocytopenia syndrome Virus in healthy persons, China, 2013

    NARCIS (Netherlands)

    Zhang Lei, Lei; Sun, J.; Yan, J.; Huakun, L.; Chai, C.Y.; Sun, Y.; Shao, B.; Jiang, J.D.; Chen, Z.; Kortekaas, J.A.; Zhang, Y.

    2014-01-01

    In June 2013, a subclinical infection with severe fever with thrombocytopenia syndrome virus (SFTSV) was detected in Zhejiang Province, China, prompting seroprevalence studies in 6 districts within the province. Of 986 healthy persons tested, 71 had IgG antibodies against SFTSV. This finding

  17. Transcriptional analysis of the ribonucleotide reductase genes in shrimp white spot syndrome virus

    NARCIS (Netherlands)

    Tsai, M.F.; Lo, C.F.; Hulten, van M.C.W.; Tzeng, H.F.; Chou, C.M.; Huang, C.J.; Wang, C.S.

    2000-01-01

    The causative agent of white spot syndrome (WSS) is a large double-stranded DNA virus, WSSV, which is probably a representative of a new genus, provisionally called Whispovirus. From previously constructed WSSV genomic libraries of a Taiwan WSSV isolate, clones with open reading frames (ORFs) that

  18. White spot syndrome virus molecular epidemiology: relation with shrimp farming and disease outbreaks

    NARCIS (Netherlands)

    Tran Thi Tuyet, H.

    2012-01-01

    White spot syndrome virus (WSSV), the causative agent of white spot disease (WSD), has been responsible for most shrimp production losses around the world since the early 1990s. Previous research has focused mainly on the characterization of WSSV genomic variation to gain a better insight in the

  19. Transmission of white spot syndrome virus (WSSV) from Dendronereis spp. (Peters) (Nereididae) to penaeid shrimp

    NARCIS (Netherlands)

    Haryadi, D.; Verreth, J.A.J.; Verdegem, M.C.J.; Vlak, J.M.

    2015-01-01

    Dendronereis spp. (Peters) (Nereididae) is a common polychaete in shrimp ponds built on intertidal land and is natural food for shrimp in traditionally managed ponds in Indonesia. White spot syndrome virus (WSSV), an important viral pathogen of the shrimp, can replicate in this polychaete (Desrina

  20. A Survey of Protein Structures from Archaeal Viruses

    Directory of Open Access Journals (Sweden)

    Nikki Dellas

    2013-01-01

    Full Text Available Viruses that infect the third domain of life, Archaea, are a newly emerging field of interest. To date, all characterized archaeal viruses infect archaea that thrive in extreme conditions, such as halophilic, hyperthermophilic, and methanogenic environments. Viruses in general, especially those replicating in extreme environments, contain highly mosaic genomes with open reading frames (ORFs whose sequences are often dissimilar to all other known ORFs. It has been estimated that approximately 85% of virally encoded ORFs do not match known sequences in the nucleic acid databases, and this percentage is even higher for archaeal viruses (typically 90%–100%. This statistic suggests that either virus genomes represent a larger segment of sequence space and/or that viruses encode genes of novel fold and/or function. Because the overall three-dimensional fold of a protein evolves more slowly than its sequence, efforts have been geared toward structural characterization of proteins encoded by archaeal viruses in order to gain insight into their potential functions. In this short review, we provide multiple examples where structural characterization of archaeal viral proteins has indeed provided significant functional and evolutionary insight.

  1. Modulation of type I interferon induction by porcine reproductive and respiratory syndrome virus and degradation of CREB-binding protein by non-structural protein 1 in MARC-145 and HeLa cells

    International Nuclear Information System (INIS)

    Kim, Oekyung; Sun Yan; Lai, Frances W.; Song Cheng; Yoo, Dongwan

    2010-01-01

    Porcine reproductive and respiratory syndrome (PRRS) is an emerged disease of swine characterized by negligible response of type I IFNs and viral persistence. We show that the PRRSV non-structural protein 1 (Nsp1) is the viral component responsible for modulation of IFN response. Nsp1 blocked dsRNA-induced IRF3 and IFN promoter activities. Nsp1 did not block phosphorylation and nuclear translocation of IRF3 but inhibited IRF3 association with CREB-binding protein (CBP) in the nucleus. While IRF3 was stable, CBP was degraded, and CBP degradation was proteasome-dependent, suggesting that CBP degradation is not due to the protease activity of Nsp1 but an intermediary is involved. Our data suggest that the Nsp1-mediated CBP degradation inhibits the recruitment of CBP for enhanceosome assembly, leading to the block of IFN response. CBP degradation is a novel strategy for viral evasion from the host response, and Nsp1 may form a new class of viral antagonists for IFN modulation.

  2. The study of virus structure and function: a personal history

    Science.gov (United States)

    Rossmann, Michael G.

    2014-09-01

    I describe my gradually evolving role as a scientist from my birth in Frankfurt (Germany) to my education in the UK, my post-doc years and my experiences as an independent investigator at Purdue University1. I discuss the significance of my post-doctoral work in Minnesota where I had my first encounter with an electronic computer and subsequently in Cambridge where I participated in the first structure determination of proteins. After six years back in England my family moved to Indiana (USA) where my home remains to this day. At Purdue University I first studied the structure of enzymes and in the process I discovered the organization and slow evolution of protein domains, each with a specific function. With this success I started what had been on my mind already for a long time, namely the structural analysis of viruses. Initially we studied plant viruses but then switched to small RNA animal viruses, discovering that some plant and animal RNA viruses have closely similar structures and therefore presumably had a common evolutionary origin. Next I became interested in somewhat larger viruses that had lipid membrane envelopes. In turn that has led to the study of very large dsDNA viruses as big as small bacteria as well as studies of bacterial viruses that require complex molecular motors for different parts of their life cycle. While developing crystallographic techniques for the study of viruses it has become progressively more apparent that electron microscopy is an important new tool that is likely to eclipse x-ray crystallography in the next decade.

  3. Risk factors for infection of sow herds with porcine reproductive and respiratory syndrome (PRRS) virus

    DEFF Research Database (Denmark)

    Mortensen, Sten; Stryhn, Henrik; Søgaard, Rikke

    2002-01-01

    In 1992, the porcine reproductive and respiratory syndrome virus (PRRSV) of European type (PRRSV-EU) was introduced in Denmark. By 1996, the virus had spread to approximately 25% of the Danish herds. In January 1996, a modified-live vaccine based on the American type of the virus (PRRSV-US) was u......In 1992, the porcine reproductive and respiratory syndrome virus (PRRSV) of European type (PRRSV-EU) was introduced in Denmark. By 1996, the virus had spread to approximately 25% of the Danish herds. In January 1996, a modified-live vaccine based on the American type of the virus (PRRSV......-US) was used in replacement boars for Danish artificial insemination (AI) centres and from July 1996, the vaccine was used in PRRSV-EU infected herds for prevention of disease. Soon after vaccine introduction, PRRSV non-infected herds experienced outbreaks of disease due to infection with PRRSV...... in the case herds). The data were analysed using a Cox-regression model. The hazard of infection increased significantly with exposure from PRRSV-US-infected neighbouring herds, purchase of animals from herds incubating PRRSV-US infection, increasing herd size and purchase of semen from boars at PRRSV...

  4. Unique Structural Features of Influenza Virus H15 Hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Tzarum, Netanel; McBride, Ryan; Nycholat, Corwin M.; Peng, Wenjie; Paulson, James C.; Wilson, Ian A. (Scripps)

    2017-04-12

    Influenza A H15 viruses are members of a subgroup (H7-H10-H15) of group 2 hemagglutinin (HA) subtypes that include H7N9 and H10N8 viruses that were isolated from humans during 2013. The isolation of avian H15 viruses is, however, quite rare and, until recently, geographically restricted to wild shorebirds and waterfowl in Australia. The HAs of H15 viruses contain an insertion in the 150-loop (loop beginning at position 150) of the receptor-binding site common to this subgroup and a unique insertion in the 260-loop compared to any other subtype. Here, we show that the H15 HA has a high preference for avian receptor analogs by glycan array analyses. The H15 HA crystal structure reveals that it is structurally closest to H7N9 HA, but the head domain of the H15 trimer is wider than all other HAs due to a tilt and opening of the HA1 subunits of the head domain. The extended 150-loop of the H15 HA retains the conserved conformation as in H7 and H10 HAs. Furthermore, the elongated 260-loop increases the exposed HA surface and can contribute to antigenic variation in H15 HAs. Since avian-origin H15 HA viruses have been shown to cause enhanced disease in mammalian models, further characterization and immune surveillance of H15 viruses are warranted.

    IMPORTANCEIn the last 2 decades, an apparent increase has been reported for cases of human infection by emerging avian influenza A virus subtypes, including H7N9 and H10N8 viruses isolated during 2013. H15 is the other member of the subgroup of influenza A virus group 2 hemagglutinins (HAs) that also include H7 and H10. H15 viruses have been restricted to Australia, but recent isolation of H15 viruses in western Siberia suggests that they could be spread more globally via the avian flyways that converge and emanate from this region. Here we report on characterization of the three-dimensional structure and receptor specificity of the H15 hemagglutinin, revealing distinct features and specificities that can

  5. Varicella-Zoster Virus and Ramsay Hunt Syndrome

    OpenAIRE

    J Gordon Millichap

    2000-01-01

    Fifty two children, aged 2 to 15 years, diagnosed with Ramsay Hunt syndrome (RHS) in a 20 year period between 1976 and 1996 are reported from the Facial Nerve Clinic, Ehime University Hospital, Japan.

  6. Localization of influenza virus proteins to nuclear dot 10 structures in influenza virus-infected cells

    International Nuclear Information System (INIS)

    Sato, Yoshiko; Yoshioka, Kenichi; Suzuki, Chie; Awashima, Satoshi; Hosaka, Yasuhiro; Yewdell, Jonathan; Kuroda, Kazumichi

    2003-01-01

    We studied influenza virus M1 protein by generating HeLa and MDCK cell lines that express M1 genetically fused to green fluorescent protein (GFP). GFP-M1 was incorporated into virions produced by influenza virus infected MDCK cells expressing the fusion protein indicating that the fusion protein is at least partially functional. Following infection of either HeLa or MDCK cells with influenza A virus (but not influenza B virus), GFP-M1 redistributes from its cytosolic/nuclear location and accumulates in nuclear dots. Immunofluorescence revealed that the nuclear dots represent nuclear dot 10 (ND10) structures. The colocalization of authentic M1, as well as NS1 and NS2 protein, with ND10 was confirmed by immunofluorescence following in situ isolation of ND10. These findings demonstrate a previously unappreciated involvement of influenza virus with ND10, a structure involved in cellular responses to immune cytokines as well as the replication of a rapidly increasing list of viruses

  7. Structural characterization of Mumps virus fusion protein core

    International Nuclear Information System (INIS)

    Liu Yueyong; Xu Yanhui; Lou Zhiyong; Zhu Jieqing; Hu Xuebo; Gao, George F.; Qiu Bingsheng; Rao Zihe; Tien, Po

    2006-01-01

    The fusion proteins of enveloped viruses mediating the fusion between the viral and cellular membranes comprise two discontinuous heptad repeat (HR) domains located at the ectodomain of the enveloped glycoproteins. The crystal structure of the fusion protein core of Mumps virus (MuV) was determined at 2.2 A resolution. The complex is a six-helix bundle in which three HR1 peptides form a central highly hydrophobic coiled-coil and three HR2 peptides pack against the hydrophobic grooves on the surface of central coiled-coil in an oblique antiparallel manner. Fusion core of MuV, like those of simian virus 5 and human respiratory syncytium virus, forms typical 3-4-4-4-3 spacing. The similar charecterization in HR1 regions, as well as the existence of O-X-O motif in extended regions of HR2 helix, suggests a basic rule for the formation of the fusion core of viral fusion proteins

  8. Mutations within the nuclear localization signal of the porcine reproductive and respiratory syndrome virus nucleocapsid protein attenuate virus replication

    International Nuclear Information System (INIS)

    Lee, Changhee; Hodgins, Douglas; Calvert, Jay G.; Welch, Siao-Kun W.; Jolie, Rika; Yoo, Dongwan

    2006-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus replicating in the cytoplasm, but the nucleocapsid (N) protein is specifically localized to the nucleus and nucleolus in virus-infected cells. A 'pat7' motif of 41-PGKK(N/S)KK has previously been identified in the N protein as the functional nuclear localization signal (NLS); however, the biological consequences of N protein nuclear localization are unknown. In the present study, the role of N protein nuclear localization during infection was investigated in pigs using an NLS-null mutant virus. When two lysines at 43 and 44 at the NLS locus were substituted to glycines, the modified NLS with 41-PGGGNKK restricted the N protein to the cytoplasm. This NLS-null mutation was introduced into a full-length infectious cDNA clone of PRRSV. Upon transfection of cells, the NLS-null full-length clone induced cytopathic effects and produced infectious progeny. The NLS-null virus grew to a titer 100-fold lower than that of wild-type virus. To examine the response to NLS-null PRRSV in the natural host, three groups of pigs, consisting of seven animals per group, were intranasally inoculated with wild-type, placebo, or NLS-null virus, and the animals were maintained for 4 weeks. The NLS-null-infected pigs had a significantly shorter mean duration of viremia than wild-type-infected pigs but developed significantly higher titers of neutralizing antibodies. Mutations occurred at the NLS locus in one pig during viremia, and four types of mutations were identified: 41-PGRGNKK, 41-PGGRNKK, and 41-PGRRNKK, and 41-PGKKSKK. Both wild-type and NLS-null viruses persisted in the tonsils for at least 4 weeks, and the NLS-null virus persisting in the tonsils was found to be mutated to either 41-PGRGNKK or 41-PGGRNKK in all pigs. No other mutation was found in the N gene. All types of reversions which occurred during viremia and persistence were able to translocate the mutated N proteins to the nucleus, indicating a

  9. Crystal Structure of Feline Infectious Peritonitis Virus Main Protease in Complex with Synergetic Dual Inhibitors.

    Science.gov (United States)

    Wang, Fenghua; Chen, Cheng; Liu, Xuemeng; Yang, Kailin; Xu, Xiaoling; Yang, Haitao

    2016-02-15

    Coronaviruses (CoVs) can cause highly prevalent diseases in humans and animals. Feline infectious peritonitis virus (FIPV) belongs to the genus Alphacoronavirus, resulting in a lethal systemic granulomatous disease called feline infectious peritonitis (FIP), which is one of the most important fatal infectious diseases of cats worldwide. No specific vaccines or drugs have been approved to treat FIP. CoV main proteases (M(pro)s) play a pivotal role in viral transcription and replication, making them an ideal target for drug development. Here, we report the crystal structure of FIPV M(pro) in complex with dual inhibitors, a zinc ion and a Michael acceptor. The complex structure elaborates a unique mechanism of two distinct inhibitors synergizing to inactivate the protease, providing a structural basis to design novel antivirals and suggesting the potential to take advantage of zinc as an adjunct therapy against CoV-associated diseases. Coronaviruses (CoVs) have the largest genome size among all RNA viruses. CoV infection causes various diseases in humans and animals, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). No approved specific drugs or vaccinations are available to treat their infections. Here, we report a novel dual inhibition mechanism targeting CoV main protease (M(pro)) from feline infectious peritonitis virus (FIPV), which leads to lethal systemic granulomatous disease in cats. M(pro), conserved across all CoV genomes, is essential for viral replication and transcription. We demonstrated that zinc ion and a Michael acceptor-based peptidomimetic inhibitor synergistically inactivate FIPV M(pro). We also solved the structure of FIPV M(pro) complexed with two inhibitors, delineating the structural view of a dual inhibition mechanism. Our study provides new insight into the pharmaceutical strategy against CoV M(pro) through using zinc as an adjuvant therapy to enhance the efficacy of an irreversible

  10. Plant-derived chimeric virus particles for the diagnosis of primary Sjögren syndrome

    Directory of Open Access Journals (Sweden)

    Elisa eTinazzi

    2015-12-01

    Full Text Available Plants are ideal for the production of protein-based nanomaterials because they synthesize and assemble complex multimeric proteins that cannot be expressed efficiently using other platforms. Plant viruses can be thought of as self-replicating proteinaceous nanomaterials generally stable and easily produced in high titers. We used Potato virus X (PVX chimeric virus particles (CVPs and Cowpea mosaic virus (CPMV empty virus-like particles (eVLPs to display a linear peptide (lipo derived from human lipocalin , which is immunodominant in Sjögren’s syndrome (SjS and is thus recognized by autoantibodies in SjS patient serum. These virus-derived nanoparticles (VNPs were thus used to develop a diagnostic assay for SjS based on a direct enzyme linked immunosorbent assay (ELISA format. We found that PVX-lipo formulations were more sensitive than the chemically synthesized immunodominant peptide and equally specific when used to distinguish between healthy individuals and SjS patients. Our novel assay therefore allows the diagnosis of SjS using a simple, low-invasive serum test, contrasting with the invasive labial biopsy required for current tests. Our results demonstrate that nanomaterials based on plant viruses can be used as diagnostic reagents for SjS, and could also be developed for the diagnosis of other diseases.

  11. Epstein-Barr virus-induced infectious mononucleosis after two separate episodes of virus-associated hemophagocytic syndrome.

    Science.gov (United States)

    Ohno, Tatsuharu; Ueda, Yo; Kishimoto, Wataru; Arimoto-Miyamoto, Kazue; Takeoka, Tomoharu; Tsuji, Masaaki

    2009-01-01

    A 24-year-old man, who had suffered previous two episodes of non- Epstein-Barr virus (EBV)-associated hemophagocytic syndrome (HPS) at the ages of 16 and 18, developed EBV-induced infectious mononucleosis. His antibody pattern to EBV highlighted the initial infection. The disease took a self-limited course without developing into HPS. No reactivation of EBV infection was noted over the following 6 years. The patient may have attained immune competency in adulthood, which was somehow impaired during his adolescence.

  12. Solenopsis invicta virus 3: mapping of structural proteins, ribosomal frameshifting, and similarities to Acyrthosiphon pisum virus and Kelp fly virus.

    Directory of Open Access Journals (Sweden)

    Steven M Valles

    Full Text Available Solenopsis invicta virus 3 (SINV-3 is a positive-sense single-stranded RNA virus that infects the red imported fire ant, Solenopsis invicta. We show that the second open reading frame (ORF of the dicistronic genome is expressed via a frameshifting mechanism and that the sequences encoding the structural proteins map to both ORF2 and the 3' end of ORF1, downstream of the sequence that encodes the RNA-dependent RNA polymerase. The genome organization and structural protein expression strategy resemble those of Acyrthosiphon pisum virus (APV, an aphid virus. The capsid protein that is encoded by the 3' end of ORF1 in SINV-3 and APV is predicted to have a jelly-roll fold similar to the capsid proteins of picornaviruses and caliciviruses. The capsid-extension protein that is produced by frameshifting, includes the jelly-roll fold domain encoded by ORF1 as its N-terminus, while the C-terminus encoded by the 5' half of ORF2 has no clear homology with other viral structural proteins. A third protein, encoded by the 3' half of ORF2, is associated with purified virions at sub-stoichiometric ratios. Although the structural proteins can be translated from the genomic RNA, we show that SINV-3 also produces a subgenomic RNA encoding the structural proteins. Circumstantial evidence suggests that APV may also produce such a subgenomic RNA. Both SINV-3 and APV are unclassified picorna-like viruses distantly related to members of the order Picornavirales and the family Caliciviridae. Within this grouping, features of the genome organization and capsid domain structure of SINV-3 and APV appear more similar to caliciviruses, perhaps suggesting the basis for a "Calicivirales" order.

  13. Foot Structure in Boys with Down Syndrome

    Directory of Open Access Journals (Sweden)

    Ewa Puszczałowska-Lizis

    2017-01-01

    Full Text Available Introduction and Aim. Down syndrome (DS is associated with numerous developmental abnormalities, some of which cause dysfunctions of the posture and the locomotor system. The analysis of selected features of the foot structure in boys with DS versus their peers without developmental disorders is done. Materials and Methods. The podoscopic examination was performed on 30 boys with DS aged 14-15 years. A control group consisted of 30 age- and gender-matched peers without DS. Results. The feet of boys with DS are flatter compared to their healthy peers. The hallux valgus angle is not the most important feature differentiating the shape of the foot in the boys with DS and their healthy peers. In terms of the V toe setting, healthy boys had poorer results. Conclusions. Specialized therapeutic treatment in individuals with DS should involve exercises to increase the muscle strength around the foot joints, enhancing the stabilization in the joints and proprioception. Introducing orthotics and proper footwear is also important. It is also necessary to monitor the state of the foot in order to modify undertaken therapies.

  14. Bullous Variant of Sweet’s Syndrome after Herpes Zoster Virus Infection

    OpenAIRE

    Yuichiro Endo; Miki Tanioka; Hideaki Tanizaki; Minako Mori; Hiroshi Kawabata; Yoshiki Miyachi

    2011-01-01

    Aim: Cutaneous manifestations of Sweet’s syndrome (SS) are typically painful plaque-forming erythematous papules, while bullae are quite uncommon. We present a case of bullous variant of SS in acute myeloid leukaemia. In this case, herpes infection of the left mandible had preceded the development of SS. Case Report: A 75-year-old male with myelodysplastic syndrome first presented with herpes zoster virus infection-like bullae and erosive plaques on the left side of the face and neck. Treatme...

  15. Structural lability of Barley stripe mosaic virus virions.

    Directory of Open Access Journals (Sweden)

    Valentin V Makarov

    Full Text Available Virions of Barley stripe mosaic virus (BSMV were neglected for more than thirty years after their basic properties were determined. In this paper, the physicochemical characteristics of BSMV virions and virion-derived viral capsid protein (CP were analyzed, namely, the absorption and intrinsic fluorescence spectra, circular dichroism spectra, differential scanning calorimetry curves, and size distributions by dynamic laser light scattering. The structural properties of BSMV virions proved to be intermediate between those of Tobacco mosaic virus (TMV, a well-characterized virus with rigid rod-shaped virions, and flexuous filamentous plant viruses. The BSMV virions were found to be considerably more labile than expected from their rod-like morphology and a distant sequence relation of the BSMV and TMV CPs. The circular dichroism spectra of BSMV CP subunits incorporated into the virions, but not subunits of free CP, demonstrated a significant proportion of beta-structure elements, which were proposed to be localized mostly in the protein regions exposed on the virion outer surface. These beta-structure elements likely formed during virion assembly can comprise the N- and C-terminal protein regions unstructured in the non-virion CP and can mediate inter-subunit interactions. Based on computer-assisted structure modeling, a model for BSMV CP subunit structural fold compliant with the available experimental data was proposed.

  16. Emergence of a virulent porcine reproductive and respiratory syndrome virus (PRRSV 1 strain in Lower Austria

    Directory of Open Access Journals (Sweden)

    Leonie J Sinn

    2016-11-01

    Full Text Available Abstract Background In spring 2015, an outbreak of porcine reproductive and respiratory syndrome (PRRS struck Lower Austria caused by a PRRS virus (PRRSV strain spreading rapidly among both previously PRRSV negative and vaccinated pig herds. This case report describes the first well-documented emergence of the PRRSV strain responsible for this outbreak. Case presentation A PRRSV seronegative piglet-producing farm in Lower Austria encountered losses in foetuses and suckling piglets of up to 90 %; clinical signs in sows and nursery piglets included fever and reduced feed intake. Additionally, high percentages of repeat breeders and losses of up to 40 % in nursery piglets occurred. An infection with PRRSV was suggested by the detection of antibodies by enzyme linked immunosorbent assay and confirmed by quantitative real time PCR. The underlying PRRSV strain, termed AUT15-33, was isolated by passage on porcine alveolar macrophages, partially sequenced (ORF2-7 and grouped as PRRSV-1, subtype 1. In phylogenetic analysis of the genome region coding for the structural proteins, ORF2-7, AUT15-33 clustered with Belgian strains but identities were as low as 88 %. In contrast, analysis of ORF7 sequences revealed a close relationship to Croatian strains from 2012 with an identity of 94 – 95 %. Conclusions In the year following the outbreak, the same PRRSV strain was identified repeatedly in different regions of Austria. It can be speculated that the new strain has novel advantageous properties.

  17. Acute Respiratory Distress Syndrome Caused by Influenza B Virus Infection in a Patient with Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Silvio A. Ñamendys-Silva

    2011-01-01

    Full Text Available Influenza B virus infections are less common than infections caused by influenza A virus in critically ill patients, but similar mortality rates have been observed for both influenza types. Pneumonia caused by influenza B virus is uncommon and has been reported in pediatric patients and previously healthy adults. Critically ill patients with pneumonia caused by influenza virus may develop acute respiratory distress syndrome. We describe the clinical course of a critically ill patient with diffuse large B-cell lymphoma nongerminal center B-cell phenotype who developed acute respiratory distress syndrome caused by influenza B virus infection. This paper emphasizes the need to suspect influenza B virus infection in critically ill immunocompromised patients with progressive deterioration of cardiopulmonary function despite treatment with antibiotics. Early initiation of neuraminidase inhibitor and the implementation of guidelines for management of severe sepsis and septic shock should be considered.

  18. Mixed-genotype white spot syndrome virus infections of shrimp are inversely correlated with disease outbreaks in ponds

    NARCIS (Netherlands)

    Tuyet Hoa, T.T.; Zwart, M.P.; Phuong, N.T.; Oanh, D.T.H.; Jong, de M.C.M.; Vlak, J.M.

    2011-01-01

    Outbreaks of white spot syndrome virus (WSSV) in shrimp culture and its relation to virus virulence are not well understood. Here we provide evidence that the presence of WSSV mixed-genotype infections correlate with lower outbreak incidence and that disease outbreaks correlate with single-genotype

  19. siRNA injection induces sequence-independent protection in Penaeus monodon against white spot syndrome virus

    NARCIS (Netherlands)

    Westenberg, M.; Heinhuis, B.; Zuidema, D.; Vlak, J.M.

    2005-01-01

    White spot syndrome virus (WSSV) is a major disease in crustaceans, particularly shrimp, due to the current intensity of aquaculture practices. Novel strategies including vaccination to control this virus would be highly desirable. However, invertebrates lack a true adaptive immune response system

  20. On the role of the polychaete Dendronereis spp. i the transmission of white spot syndrome virus in shrimp ponds

    NARCIS (Netherlands)

    Desrina, Haryadi

    2014-01-01

    White spot syndrome virus (WSSV) is by far the most devastating shrimp virus. Control measures have lowered the WSSV incidence to various degrees, but the pathogen remains plaguing shrimp culture worldwide. Continuous exposure may cause WSSV to adapt and infect non-crustacean benthic fauna in

  1. Sensitive detection and typing of porcine reproductive and respiratory syndrome virus by RT-PCR amplification of whole viral genes

    DEFF Research Database (Denmark)

    Oleksiewicz, M.B.; Bøtner, Anette; Madsen, K.G.

    1998-01-01

    Following the recent use of a live vaccine against porcine reproductive and respiratory syndrome virus (PRRSV) in Denmark, both American (vaccine) and European-type PRRSV now coexist in Danish herds. This situation highlighted a requirement for supplementary tests for precise virus-typing. As a r...

  2. Investigation of RNA structure in satellite panicum mosaic virus

    International Nuclear Information System (INIS)

    Makino, D.L.; Day, J.; Larson, S.B.; McPherson, A.

    2006-01-01

    Three new crystal forms of satellite panicum mosaic virus (SPMV) were grown and their structures solved from X-ray diffraction data using molecular replacement techniques. The crystals were grown under conditions of pH and ionic strength that were appreciably different then those used for the original structure determination. In rhombohedral crystals grown at pH 8.5 and low ionic strength PEG 3350 solutions, Fourier syntheses revealed segments, ten amino acid residues long, of amino-terminal polypeptides not previously seen, as well as masses of electron density within concavities on the interior of the capsid, which appeared in the neighborhoods of icosahedral five- and threefold axes. The densities were compatible with secondary structural domains of RNA, and they included a segment of double helical RNA of about four to five base pairs oriented, at least approximately, along the fivefold axes. The distribution of RNA observed for SPMV appears to be distinctly different than the encapsidated nucleic acid conformation previously suggested for another satellite virus, satellite tobacco mosaic virus. This study further shows that analysis of viruses in crystals grown under different chemical conditions may reveal additional information regarding the structure of encapsidated RNA

  3. Recombinant egg drop syndrome subunit vaccine offers an alternative to virus propagation in duck eggs.

    Science.gov (United States)

    Gutter, B; Fingerut, E; Gallili, G; Eliahu, D; Perelman, B; Finger, A; Pitcovski, J

    2008-02-01

    Egg drop syndrome (EDS) virus vaccines are routinely produced in embryonated duck eggs (Solyom et al., 1982). This procedure poses the risk of dissemination of pathogens, such as avian influenza virus, as the eggs used are not from specific pathogen free birds. To address this problem, the knob and part of the shaft domain of the fibre protein of the EDS virus (termed knob-s) were expressed in Escherichia coli and assessed as a subunit vaccine. A single vaccination with the recombinant protein induced the production of anti-EDS virus antibodies, as detected by haemagglutination inhibition, enzyme-linked immunosorbent assay and virus neutralization tests, for at least 20 weeks. A positive correlation was demonstrated between these three assays. A dose-response assessment showed that the vaccine was effective over the range of 2 to 64 microg protein per dose. Two vaccinations with the recombinant protein, administered before the onset of lay, induced high haemagglutination inhibition antibody titres, comparable with those induced by an inactivated whole-virus vaccine. The vaccine did not have any adverse effects on egg production, quality or weight. The present study has shown that two vaccinations with the recombinant knob-s protein elicited high neutralizing antibody titres that persisted for more than 50 weeks of lay.

  4. Effect of porcine reproductive and respiratory syndrome virus (PRRSV) on alveolar lung macrophage survival and function

    DEFF Research Database (Denmark)

    Oleksiewicz, Martin B.; Nielsen, Jens

    1999-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) recently emerged as an important cause of reproductive disorders and pneumonia in domestic pigs throughout the world. Acute cytocidal replication of PRRSV in alveolar lung macrophages causes the acute pneumonia; however, it remains largely...... infection in this system. In short, in our minimal system containing only a single cell type, phagocytosis-suppressive effects of PRRSV infection were detected, that acted at the culture level by reducing the total number of alveolar lung macrophages....

  5. European brown hare syndrome virus in free-ranging European brown hares from Argentina

    DEFF Research Database (Denmark)

    Frolich, K.; Kujawski, G.E.J.G.; Rudolph, M.

    2003-01-01

    From 1998 to 2000, serum samples of 80 shot European brown hares (Lepus europaeus) from Argentina were examined for antibodies against European brown hare syndrome virus (EBHSV) and 80 spleen samples were tested for EBHSV-antigen by enzyme linked immunosorbent assay (ELISA). Nine hares were posit...... in these hares. This is the first report of antibodies to EBHSV, EBHSV-antigen, and electron microscopy findings in free-ranging European brown hares from South America....

  6. Comparison of the structures of three circoviruses: chicken anemia virus, porcine circovirus type 2, and beak and feather disease virus.

    Science.gov (United States)

    Crowther, R A; Berriman, J A; Curran, W L; Allan, G M; Todd, D

    2003-12-01

    Circoviruses are small, nonenveloped icosahedral animal viruses characterized by circular single-stranded DNA genomes. Their genomes are the smallest possessed by animal viruses. Infections with circoviruses, which can lead to economically important diseases, frequently result in virus-induced damage to lymphoid tissue and immunosuppression. Within the family Circoviridae, different genera are distinguished by differences in genomic organization. Thus, Chicken anemia virus is in the genus Gyrovirus, while porcine circoviruses and Beak and feather disease virus belong to the genus CIRCOVIRUS: Little is known about the structures of circoviruses. Accordingly, we investigated the structures of these three viruses with a view to determining whether they are related. Three-dimensional maps computed from electron micrographs showed that all three viruses have a T=1 organization with capsids formed from 60 subunits. Porcine circovirus type 2 and beak and feather disease virus show similar capsid structures with flat pentameric morphological units, whereas chicken anemia virus has stikingly different protruding pentagonal trumpet-shaped units. It thus appears that the structures of viruses in the same genus are related but that those of viruses in different genera are unrelated.

  7. 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.

  8. Infectious mononucleosis-like syndrome probably attributable to Coxsackie A virus infection.

    Science.gov (United States)

    Cunha, Burke A; Mickail, Nardeen; Petelin, Andrew P

    2012-01-01

    Infectious mononucleosis (IM) is a clinical syndrome most often attributable to Epstein-Barr virus (EBV). Characteristic clinical features of EBV IM include bilateral upper lid edema, exudative or nonexudative pharyngitis, bilateral posterior cervical adenopathy, and splenomegaly ± maculopapular rash. Laboratory features of EBV IM include atypical lymphocytes and elevated levels of serum transaminases. Leukopenia and thrombocytopenia are not uncommon. The syndrome of IM may also be attributable to other infectious diseases, eg, cytomegalovirus (CMV), human herpes virus-6 (HHV-6), or Toxoplasma gondii. Less commonly, viral hepatitis, leptospirosis, brucellosis, or parvovirus B(19) may present as an IM-like infection. To the best of our knowledge, only 2 cases of IM-like infections attributable to Coxsackie B viruses (B(3) and B(4)) have been reported. We present the first reported case of an IM-like syndrome with sore throat, fatigue, atypical lymphocytes, and elevated levels of serum transaminases likely due to Coxsackie A in an immunocompetent adult. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Comparative analysis of signature genes in porcine reproductive and respiratory syndrome virus (PRRSV)-infected porcine monocyte-derived dendritic cells at differential activation statuses

    Science.gov (United States)

    Activation statuses of monocytic cells, e.g. monocytes, macrophages and dendritic cells (DCs), are critically important for antiviral immunity. In particular, some devastating viruses, including porcine reproductive and respiratory syndrome virus (PRRSV), are capable of directly infecting these cell...

  10. Design, development and experimental trialof a tailored cytotoxic T-cell vaccine againstPorcine Reproductive and RespiratorySyndrome Virus-2

    DEFF Research Database (Denmark)

    Welner, Simon

    Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important threats against the global swine production industry. The virus infects alveolar macrophages that leads to respiratory distress, fever, pneumonia and gives way to secondary respiratory pathogens. Infection...

  11. Crystal Structure of the Marburg Virus VP35 Oligomerization Domain

    Energy Technology Data Exchange (ETDEWEB)

    Bruhn, Jessica F.; Kirchdoerfer, Robert N.; Urata, Sarah M.; Li, Sheng; Tickle, Ian J.; Bricogne, Gérard; Saphire, Erica Ollmann (Scripps); (Globel Phasing); (UCSD)

    2016-11-09

    ABSTRACT

    Marburg virus (MARV) is a highly pathogenic filovirus that is classified in a genus distinct from that of Ebola virus (EBOV) (generaMarburgvirusandEbolavirus, respectively). Both viruses produce a multifunctional protein termed VP35, which acts as a polymerase cofactor, a viral protein chaperone, and an antagonist of the innate immune response. VP35 contains a central oligomerization domain with a predicted coiled-coil motif. This domain has been shown to be essential for RNA polymerase function. Here we present crystal structures of the MARV VP35 oligomerization domain. These structures and accompanying biophysical characterization suggest that MARV VP35 is a trimer. In contrast, EBOV VP35 is likely a tetramer in solution. Differences in the oligomeric state of this protein may explain mechanistic differences in replication and immune evasion observed for MARV and EBOV.

    IMPORTANCEMarburg virus can cause severe disease, with up to 90% human lethality. Its genome is concise, only producing seven proteins. One of the proteins, VP35, is essential for replication of the viral genome and for evasion of host immune responses. VP35 oligomerizes (self-assembles) in order to function, yet the structure by which it assembles has not been visualized. Here we present two crystal structures of this oligomerization domain. In both structures, three copies of VP35 twist about each other to form a coiled coil. This trimeric assembly is in contrast to tetrameric predictions for VP35 of Ebola virus and to known structures of homologous proteins in the measles, mumps, and Nipah viruses. Distinct oligomeric states of the Marburg and Ebola virus VP35 proteins may explain differences between them in polymerase function and immune evasion. These findings may provide a more accurate understanding of the

  12. Structure of the Nucleoprotein Binding Domain of Mokola Virus Phosphoprotein▿

    Science.gov (United States)

    Assenberg, René; Delmas, Olivier; Ren, Jingshan; Vidalain, Pierre-Olivier; Verma, Anil; Larrous, Florence; Graham, Stephen C.; Tangy, Frédéric; Grimes, Jonathan M.; Bourhy, Hervé

    2010-01-01

    Mokola virus (MOKV) is a nonsegmented, negative-sense RNA virus that belongs to the Lyssavirus genus and Rhabdoviridae family. MOKV phosphoprotein P is an essential component of the replication and transcription complex and acts as a cofactor for the viral RNA-dependent RNA polymerase. P recruits the viral polymerase to the nucleoprotein-bound viral RNA (N-RNA) via an interaction between its C-terminal domain and the N-RNA complex. Here we present a structure for this domain of MOKV P, obtained by expression of full-length P in Escherichia coli, which was subsequently truncated during crystallization. The structure has a high degree of homology with P of rabies virus, another member of Lyssavirus genus, and to a lesser degree with P of vesicular stomatitis virus (VSV), a member of the related Vesiculovirus genus. In addition, analysis of the crystal packing of this domain reveals a potential binding site for the nucleoprotein N. Using both site-directed mutagenesis and yeast two-hybrid experiments to measure P-N interaction, we have determined the relative roles of key amino acids involved in this interaction to map the region of P that binds N. This analysis also reveals a structural relationship between the N-RNA binding domain of the P proteins of the Rhabdoviridae and the Paramyxoviridae. PMID:19906936

  13. Macular structural characteristics in children with Down syndrome.

    Science.gov (United States)

    O'Brien, Scott; Wang, Jingyun; Smith, Heather A; Donaldson, Dana L; Haider, Kathryn M; Roberts, Gavin J; Sprunger, Derek T; Neely, Daniel E; Plager, David A

    2015-12-01

    This prospective study aimed to investigate macular structural characteristics in children with Down syndrome compared to those in healthy children. Two groups of children (aged 6-16 years) were enrolled: children with Down syndrome (Down syndrome group, N = 17) and age-matched healthy children who were full-term at birth (control group, N = 18). Eligible patients had visual acuity of 20/100 or better and gestational age at birth of ≥ 36 weeks. Fourier domain optical coherence tomography was used for imaging of the macular retinal structure, and retinal volume scans centered on the macula were obtained. Central subfield thickness (CST) and the thickness of the inner and outer retinal layer regions were analyzed using the instrument's segmentation software. The analysis of data is provided for the right eye only, since there was no significant difference between right and left eyes for either the Down syndrome or control groups. Children in the Down syndrome group generally had identifiable retinal structure. The CST for the full retina and inner and outer retinal layers were all significantly greater in the Down syndrome group than the control group (independent t test, all p syndrome had macular thickness outside the normal range. Visual acuity in the Down syndrome group was not directly correlated with increased CST (t = 1.288, r = 0.326, p = 0.202). On average, CST in the Down syndrome group was greater than that in the control group, suggesting abnormal macular development in children with Down syndrome.

  14. Comparison of self-processing of foot-and-mouth disease virus leader proteinase and porcine reproductive and respiratory syndrome virus leader proteinase nsp1α

    Energy Technology Data Exchange (ETDEWEB)

    Steinberger, Jutta [Max F. Perutz Laboratories, Medical University of Vienna, Department of Medical Biochemistry, Dr. Bohr-Gasse 9/3, A-1030 Vienna (Austria); Kontaxis, Georg [Max F. Perutz Laboratories, University of Vienna, Department of Structural and Computational Biology, Campus Vienna Biocenter 5, A-1030 Vienna (Austria); Rancan, Chiara [Helmholtz Zentrum München, Department of Gene Vectors, Haematologikum, Marchioninistrasse 25, D-81377 Munich (Germany); Skern, Tim, E-mail: timothy.skern@meduniwien.ac.at [Max F. Perutz Laboratories, Medical University of Vienna, Department of Medical Biochemistry, Dr. Bohr-Gasse 9/3, A-1030 Vienna (Austria)

    2013-09-01

    The foot-and-mouth disease virus leader proteinase (Lb{sup pro}) cleaves itself off the nascent viral polyprotein. NMR studies on the monomeric variant Lb{sup pro} L200F provide structural evidence for intramolecular self-processing. {sup 15}N-HSQC measurements of Lb{sup pro} L200F showed specifically shifted backbone signals in the active and substrate binding sites compared to the monomeric variant sLb{sup pro}, lacking six C-terminal residues. This indicates transient intramolecular interactions between the C-terminal extension (CTE) of one molecule and its own active site. Contrastingly, the porcine reproductive and respiratory syndrome virus (PRRSV) leader proteinase nsp1α, with a papain-like fold like Lb{sup pro}, stably binds its own CTE. Parts of the β-sheet domains but none of the α-helical domains of Lb{sup pro} and nsp1α superimpose; consequently, the α-helical domain of nsp1α is oriented differently relative to its β-sheet domain. This provides a large interaction surface for the CTE with the globular domain, stabilising the intramolecular complex. Consequently, self-processing inactivates nsp1α but not Lb{sup pro}. - Highlights: • We examine self-processing of the leader protease of foot-and-mouth disease virus. • NMR analysis strongly supports intramolecular self-processing. • Self-processing is a dynamic process with no stable complex. • Structural comparison with nsp1α of PRRSV which forms stable intramolecular complex. • Subdomain orientation explains differences in stability of intramolecular complexes.

  15. Comparison of self-processing of foot-and-mouth disease virus leader proteinase and porcine reproductive and respiratory syndrome virus leader proteinase nsp1α

    International Nuclear Information System (INIS)

    Steinberger, Jutta; Kontaxis, Georg; Rancan, Chiara; Skern, Tim

    2013-01-01

    The foot-and-mouth disease virus leader proteinase (Lb pro ) cleaves itself off the nascent viral polyprotein. NMR studies on the monomeric variant Lb pro L200F provide structural evidence for intramolecular self-processing. 15 N-HSQC measurements of Lb pro L200F showed specifically shifted backbone signals in the active and substrate binding sites compared to the monomeric variant sLb pro , lacking six C-terminal residues. This indicates transient intramolecular interactions between the C-terminal extension (CTE) of one molecule and its own active site. Contrastingly, the porcine reproductive and respiratory syndrome virus (PRRSV) leader proteinase nsp1α, with a papain-like fold like Lb pro , stably binds its own CTE. Parts of the β-sheet domains but none of the α-helical domains of Lb pro and nsp1α superimpose; consequently, the α-helical domain of nsp1α is oriented differently relative to its β-sheet domain. This provides a large interaction surface for the CTE with the globular domain, stabilising the intramolecular complex. Consequently, self-processing inactivates nsp1α but not Lb pro . - Highlights: • We examine self-processing of the leader protease of foot-and-mouth disease virus. • NMR analysis strongly supports intramolecular self-processing. • Self-processing is a dynamic process with no stable complex. • Structural comparison with nsp1α of PRRSV which forms stable intramolecular complex. • Subdomain orientation explains differences in stability of intramolecular complexes

  16. Emergence of Epidemic Zika Virus Transmission and Congenital Zika Syndrome: Are Recently Evolved Traits to Blame?

    Directory of Open Access Journals (Sweden)

    Scott C. Weaver

    2017-01-01

    Full Text Available The mechanisms responsible for the dramatic emergence of Zika virus (ZIKV, accompanied by congenital Zika syndrome and Guillain-Barré syndrome (GBS, remain unclear. However, two hypotheses are prominent: (i evolution for enhanced urban transmission via adaptation to mosquito vectors, or for enhanced human infection to increase amplification, or (ii the stochastic introduction of ZIKV into large, naive human populations in regions with abundant Aedes aegypti populations, leading to enough rare, severe infection outcomes for their first recognition. Advances in animal models for human infection combined with improvements in serodiagnostics, better surveillance, and reverse genetic approaches should provide more conclusive evidence of whether mosquito transmission or human pathogenesis changed coincidentally with emergence in the South Pacific and the Americas. Ultimately, understanding the mechanisms of epidemic ZIKV emergence, and its associated syndromes, is critical to predict future risks as well as to target surveillance and control measures in key locations.

  17. Extensive severe fever with thrombocytopenia syndrome virus contamination in surrounding environment in patient rooms.

    Science.gov (United States)

    Ryu, B-H; Kim, J Y; Kim, T; Kim, M-C; Kim, M J; Chong, Y-P; Lee, S-O; Choi, S-H; Kim, Y S; Woo, J H; Kim, S-H

    2018-01-31

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease in Korea and China. Although there is previous evidence of person-to-person transmission via direct contact with body fluids, the role of environmental contamination by SFTS virus (SFTSV) in healthcare settings has not been established. We therefore investigated the contamination of the healthcare environment by SFTSV. We investigated the possible contamination of hospital air and surfaces with SFTSV transmission by collecting air and swabbing environmental surface samples in two hospitals treating six SFTS patients between March and September 2017. The samples were tested using real-time RT-PCR for SFTS M and S segments. Of the six SFTS patients, four received mechanical ventilation and three died. Five rooms were occupied by those using mechanical ventilation or total plasma exchange therapy in isolation rooms without negative pressure and one room was occupied by a patient bedridden due to SFTS. SFTSV was detected in 14 (21%) of 67 swab samples. Five of 24 swab samples were obtained from fomites including stethoscopes, and 9 of 43 were obtained from fixed structures including doorknobs and bed guardrails. Some samples from fixed structures such as television monitors and sink tables were obtained in areas remote from the patients. SFTSV RNA was not detected in five air samples from three patients' rooms. Our data suggest that SFTSV contamination was extensive in surrounding environments in SFTS patients' rooms. Therefore, more strict isolation methods and disinfecting procedures should be considered when managing SFTS patients. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  18. NMR Structure of the Myristylated Feline Immunodeficiency Virus Matrix Protein

    Directory of Open Access Journals (Sweden)

    Lola A. Brown

    2015-04-01

    Full Text Available Membrane targeting by the Gag proteins of the human immunodeficiency viruses (HIV types-1 and -2 is mediated by Gag’s N-terminally myristylated matrix (MA domain and is dependent on cellular phosphatidylinositol-4,5-bisphosphate [PI(4,5P2]. To determine if other lentiviruses employ a similar membrane targeting mechanism, we initiated studies of the feline immunodeficiency virus (FIV, a widespread feline pathogen with potential utility for development of human therapeutics. Bacterial co-translational myristylation was facilitated by mutation of two amino acids near the amino-terminus of the protein (Q5A/G6S; myrMAQ5A/G6S. These substitutions did not affect virus assembly or release from transfected cells. NMR studies revealed that the myristyl group is buried within a hydrophobic pocket in a manner that is structurally similar to that observed for the myristylated HIV-1 protein. Comparisons with a recent crystal structure of the unmyristylated FIV protein [myr(-MA] indicate that only small changes in helix orientation are required to accommodate the sequestered myr group. Depletion of PI(4,5P2 from the plasma membrane of FIV-infected CRFK cells inhibited production of FIV particles, indicating that, like HIV, FIV hijacks the PI(4,5P2 cellular signaling system to direct intracellular Gag trafficking during virus assembly.

  19. NMR structure of the myristylated feline immunodeficiency virus matrix protein.

    Science.gov (United States)

    Brown, Lola A; Cox, Cassiah; Baptiste, Janae; Summers, Holly; Button, Ryan; Bahlow, Kennedy; Spurrier, Vaughn; Kyser, Jenna; Luttge, Benjamin G; Kuo, Lillian; Freed, Eric O; Summers, Michael F

    2015-04-30

    Membrane targeting by the Gag proteins of the human immunodeficiency viruses (HIV types-1 and -2) is mediated by Gag's N-terminally myristylated matrix (MA) domain and is dependent on cellular phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. To determine if other lentiviruses employ a similar membrane targeting mechanism, we initiated studies of the feline immunodeficiency virus (FIV), a widespread feline pathogen with potential utility for development of human therapeutics. Bacterial co-translational myristylation was facilitated by mutation of two amino acids near the amino-terminus of the protein (Q5A/G6S; myrMAQ5A/G6S). These substitutions did not affect virus assembly or release from transfected cells. NMR studies revealed that the myristyl group is buried within a hydrophobic pocket in a manner that is structurally similar to that observed for the myristylated HIV-1 protein. Comparisons with a recent crystal structure of the unmyristylated FIV protein [myr(-)MA] indicate that only small changes in helix orientation are required to accommodate the sequestered myr group. Depletion of PI(4,5)P2 from the plasma membrane of FIV-infected CRFK cells inhibited production of FIV particles, indicating that, like HIV, FIV hijacks the PI(4,5)P2 cellular signaling system to direct intracellular Gag trafficking during virus assembly.

  20. Primary EBV infection induces an expression profile distinct from other viruses but similar to hemophagocytic syndromes.

    Directory of Open Access Journals (Sweden)

    Samantha K Dunmire

    Full Text Available Epstein-Barr Virus (EBV causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza, respiratory syncytial virus (RSV, human rhinovirus (HRV, attenuated yellow fever virus (YFV, and Dengue fever virus (DENV, revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including MX1, HERC5, and OAS1, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans.

  1. Primary EBV Infection Induces an Expression Profile Distinct from Other Viruses but Similar to Hemophagocytic Syndromes

    Science.gov (United States)

    Dunmire, Samantha K.; Odumade, Oludare A.; Porter, Jean L.; Reyes-Genere, Juan; Schmeling, David O.; Bilgic, Hatice; Fan, Danhua; Baechler, Emily C.; Balfour, Henry H.; Hogquist, Kristin A.

    2014-01-01

    Epstein-Barr Virus (EBV) causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza), respiratory syncytial virus (RSV), human rhinovirus (HRV), attenuated yellow fever virus (YFV), and Dengue fever virus (DENV), revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including MX1, HERC5, and OAS1, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans. PMID:24465555

  2. Neutralization of White Spot Syndrome Virus by Monoclonal Antibodies against Viral Envelope Proteins

    Directory of Open Access Journals (Sweden)

    Hsiu-Hui Shih

    2004-09-01

    Full Text Available Two monoclonal antibodies (MAbs recognizing envelope proteins of the white spot syndrome virus (WSSV, 6E1 against VP28 and 3E8 against VP19, were applied to demonstrate their neutralizing ability to this virus by using both in vitro and in vivo assays. Mixtures of MAb 6E1 with virus filtrate were inoculated into the primary explant monolayer culture derived from the lymphoid Oka organs of Penaeus monodon. Mab was likely to neutralize the infectivity of virus to monolayer since cytopathic effects were apparently blocked in experiment group. WSSV was titrated using Blue-Cell ELISA and the neutralizing index was calculated to be 6.90 for 6EI and 5.83 for 3E8. Neutralized virus fluids injected intramuscularly into post larvae of P. monodon. The shrimp in the positive control, which were injected with WSSV only showed an increasing mortality and a 100% mortality was reached at day 34, whereas no shrimp died in the negative control. The mortality for 6E1 was 6.7% and for 3E8 was 13.3%. These results suggest that Mabs recognizing the WSSV envelope proteins could neutralize viral infectivity to both cultured cells and shrimp.

  3. The structure of melon necrotic spot virus determined at 2.8 Å resolution

    International Nuclear Information System (INIS)

    Wada, Yasunobu; Tanaka, Hideaki; Yamashita, Eiki; Kubo, Chikako; Ichiki-Uehara, Tamaki; Nakazono-Nagaoka, Eiko; Omura, Toshihiro; Tsukihara, Tomitake

    2007-01-01

    The structure of melon necrotic spot virus is reported. The structure of melon necrotic spot virus (MNSV) was determined at 2.8 Å resolution. Although MNSV is classified into the genus Carmovirus of the family Tombusviridae, the three-dimensional structure of MNSV showed a higher degree of similarity to tomato bushy stunt virus (TBSV), which belongs to the genus Tombusvirus, than to carnation mottle virus (CMtV), turnip crinkle virus (TCV) or cowpea mottle virus (CPMtV) from the genus Carmovirus. Thus, the classification of the family Tombusviridae at the genus level conflicts with the patterns of similarity among coat-protein structures. MNSV is one of the viruses belonging to the genera Tombusvirus or Carmovirus that are naturally transmitted in the soil by zoospores of fungal vectors. The X-ray structure of MNSV provides us with a representative structure of viruses transmitted by fungi

  4. Hepatitis C, human immunodeficiency virus and metabolic syndrome: interactions.

    Science.gov (United States)

    Kotler, Donald P

    2009-03-01

    Significant concerns have been raised about the metabolic effects of antiretroviral medication, including the classic triad of dyslipidaemia, insulin resistance (IR) and characteristic alterations in fat distribution (lipoatrophy and lipohypertrophy). Co-infection with hepatitis C appears to exacerbate IR, reduce serum lipids and induce prothrombotic changes in the treated human immunodeficiency virus patient. The effects of co-infection are complex. While combination antiretroviral therapy has been shown to be associated with an increased risk of cardiovascular events through promotion of dyslipidaemia, IR and fat redistribution, co-infection exacerbates IR while reducing serum lipids. Co-infection also promotes a prothrombotic state characterized by endothelial dysfunction and platelet activation, which may enhance risk for cardiovascular disease. Consideration must be given to selection of appropriate treatment regimens and timing of therapy in co-infected patients to minimize metabolic derangements and, ultimately, reduce cardiovascular risk.

  5. Functional RNA structures throughout the Hepatitis C Virus genome.

    Science.gov (United States)

    Adams, Rebecca L; Pirakitikulr, Nathan; Pyle, Anna Marie

    2017-06-01

    The single-stranded Hepatitis C Virus (HCV) genome adopts a set of elaborate RNA structures that are involved in every stage of the viral lifecycle. Recent advances in chemical probing, sequencing, and structural biology have facilitated analysis of RNA folding on a genome-wide scale, revealing novel structures and networks of interactions. These studies have underscored the active role played by RNA in every function of HCV and they open the door to new types of RNA-targeted therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Transmission of White Spot Syndrome Virus and Possible Use of Physical Barrier as Preventive Measure (Transmisi White Spot Syndrome Virus dan Penggunaan Barier Fisik Sebagai Upaya Pencegahan

    Directory of Open Access Journals (Sweden)

    Arief Taslihan

    2013-06-01

    Full Text Available Penyakit bercak putih viral hingga saat ini masih menjadi masalah dalam budidaya udang. Munculnya penyakit tersebut diikuti kematian massal, sehingga menimbulkan kerugian besar. Penyakit yang disebabkan white spots syndrome virus (WSSV menular cepat dari satu petakan tambak ke petakan lain. Penelitian bertujuan melakukan uji kuantitas WSSV pada transmisi virus baik melalui air dan kohabitasi. Metode penelitian adalah bioassay dilakukan skala laboratorium. Penularan melalui air disimulasi pada akuarium disekat dengan 3 jenis kasa berukuran pori berbeda, yaitu 300μ, 700μ dan 2 mm. Kohabitasi dilakukan dengan memelihara udang terinfeksi WSSV secara buatan dengan udang dan moluska sehat. Hasil penelitian didapatkan bahwa WSSV menimbulkan infeksi pada udang sehat yang ditempatkan terpisah dari udang sakit menggunakan sekat kasa. Virus bercak putih juga menular secara kohabitasi udang sakit dengan udang sehat baik dari udang windu ke udang windu (sejenis maupun udang windu ke udang vannamei (berlainan jenis. Hasi penelitian menunjukkan bahwa trisipan bukan karier WSSV, karena tidak menularkan. Analisis LT-50 (lethal time 50% didapatkan bahwa udang yang diuji tantang WSSV melalui inkubasi dengan air mengandung ekstrak WSSV didapatkan konsentrasi 2,75x102 WSSV copy.mL-1 menyebabkan kematian 50% dalam waktu 108 jam atau hampir lima hari. Penggunaan kasa putih meskipun tidak sepenuhnya menahan, dapat menghambat sebagian transmisi WSSV. Hasil kajian memberikan gambaran tentang kecepatan penyebaran WSSV di lingkungan budidaya udang serta memberikan panduan bagaimana mengendalikan WSSV. Kata kunci: penyakit, transmisi WSSV, udang, kohabitasi, trisipan White spot viral disease has devastated shrimp industry in Indonesia. The emergence of this disease is always followed by massive death causing huge losses. Disease is caused by a virus namely White spots syndrome virus (WSSV is rapidly transmitted from one pond to other ponds. This study aims to quantify

  7. Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study.

    Science.gov (United States)

    Cao-Lormeau, V M; Blake, A; Mons, S; Lastere, S; Roche, C; Vanhomwegen, J; Dub, T; Baudouin, L; Teissier, A; Larre, P; Vial, A L; Decam, C; Choumet, V; Halstead, S K; Willison, H J; Musset, L; Manuguerra, J C; Despres, P; Fournier, E; Mallet, H P; Musso, D; Fontanet, A; Neil, J; Ghawché, F

    2016-04-09

    Between October, 2013, and April, 2014, French Polynesia experienced the largest Zika virus outbreak ever described at that time. During the same period, an increase in Guillain-Barré syndrome was reported, suggesting a possible association between Zika virus and Guillain-Barré syndrome. We aimed to assess the role of Zika virus and dengue virus infection in developing Guillain-Barré syndrome. In this case-control study, cases were patients with Guillain-Barré syndrome diagnosed at the Centre Hospitalier de Polynésie Française (Papeete, Tahiti, French Polynesia) during the outbreak period. Controls were age-matched, sex-matched, and residence-matched patients who presented at the hospital with a non-febrile illness (control group 1; n=98) and age-matched patients with acute Zika virus disease and no neurological symptoms (control group 2; n=70). Virological investigations included RT-PCR for Zika virus, and both microsphere immunofluorescent and seroneutralisation assays for Zika virus and dengue virus. Anti-glycolipid reactivity was studied in patients with Guillain-Barré syndrome using both ELISA and combinatorial microarrays. 42 patients were diagnosed with Guillain-Barré syndrome during the study period. 41 (98%) patients with Guillain-Barré syndrome had anti-Zika virus IgM or IgG, and all (100%) had neutralising antibodies against Zika virus compared with 54 (56%) of 98 in control group 1 (pZika virus IgM and 37 (88%) had experienced a transient illness in a median of 6 days (IQR 4-10) before the onset of neurological symptoms, suggesting recent Zika virus infection. Patients with Guillain-Barré syndrome had electrophysiological findings compatible with acute motor axonal neuropathy (AMAN) type, and had rapid evolution of disease (median duration of the installation and plateau phases was 6 [IQR 4-9] and 4 days [3-10], respectively). 12 (29%) patients required respiratory assistance. No patients died. Anti-glycolipid antibody activity was found in 13

  8. Three-dimensional structure of Rubella virus factories

    International Nuclear Information System (INIS)

    Fontana, Juan; Lopez-Iglesias, Carmen; Tzeng, Wen-Ping; Frey, Teryl K.; Fernandez, Jose J.; Risco, Cristina

    2010-01-01

    Viral factories are complex structures in the infected cell where viruses compartmentalize their life cycle. Rubella virus (RUBV) assembles factories by recruitment of rough endoplasmic reticulum (RER), mitochondria and Golgi around modified lysosomes known as cytopathic vacuoles or CPVs. These organelles contain active replication complexes that transfer replicated RNA to assembly sites in Golgi membranes. We have studied the structure of RUBV factory in three dimensions by electron tomography and freeze-fracture. CPVs contain stacked membranes, rigid sheets, small vesicles and large vacuoles. These membranes are interconnected and in communication with the endocytic pathway since they incorporate endocytosed BSA-gold. RER and CPVs are coupled through protein bridges and closely apposed membranes. Golgi vesicles attach to the CPVs but no tight contacts with mitochondria were detected. Immunogold labelling confirmed that the mitochondrial protein p32 is an abundant component around and inside CPVs where it could play important roles in factory activities.

  9. Hepatopulmonary syndrome in a patient with AIDS and virus C cirrhosis (viral cirrhosis type C); Sindrome hepatopulmonar em paciente com cirrose por virus C e SIDA

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Maria Angelica; Gazzana, Marcelo Basso [Hospital de Clinicas de Porto Alegre, RS (Brazil). Servico de Pneumologia; Barreto, Sergio Saldanha Menna; Knorst, Marli Maria [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Faculdade de Medicina. Dept. de Medicina Interna

    2001-02-01

    Hepatopulmonary syndrome is characterized by a triad consisting of liver disorder, pulmonary vascular dilatation, and hypoxaemia. No case of hepatopulmonary syndrome associated with AIDS has been reported so far. In this study, the authors report the case of a 43-year woman with AIDS and virus C cirrhosis taking prophylactic cotrimoxazole for pneumocystosis and retroviral therapy. Upon admission, the patient presented dyspnoea, cyanosis, digital clubbing, vascular spiders, and normal chest examination. Chest X-ray revealed bilateral interstitial infiltration and evidenced increased alveolar-arterial gradient and liver function impairment. Intrapulmonary shunt was evidenced by contrast-enhanced echocardiography and radionuclide perfusion scanning, thus confirming hepatopulmonary syndrome. (author)

  10. Structure of deformed wing virus, a major honey bee pathogen.

    Science.gov (United States)

    Škubník, Karel; Nováček, Jiří; Füzik, Tibor; Přidal, Antonín; Paxton, Robert J; Plevka, Pavel

    2017-03-21

    The worldwide population of western honey bees ( Apis mellifera ) is under pressure from habitat loss, environmental stress, and pathogens, particularly viruses that cause lethal epidemics. Deformed wing virus (DWV) from the family Iflaviridae , together with its vector, the mite Varroa destructor , is likely the major threat to the world's honey bees. However, lack of knowledge of the atomic structures of iflaviruses has hindered the development of effective treatments against them. Here, we present the virion structures of DWV determined to a resolution of 3.1 Å using cryo-electron microscopy and 3.8 Å by X-ray crystallography. The C-terminal extension of capsid protein VP3 folds into a globular protruding (P) domain, exposed on the virion surface. The P domain contains an Asp-His-Ser catalytic triad that is, together with five residues that are spatially close, conserved among iflaviruses. These residues may participate in receptor binding or provide the protease, lipase, or esterase activity required for entry of the virus into a host cell. Furthermore, nucleotides of the DWV RNA genome interact with VP3 subunits. The capsid protein residues involved in the RNA binding are conserved among honey bee iflaviruses, suggesting a putative role of the genome in stabilizing the virion or facilitating capsid assembly. Identifying the RNA-binding and putative catalytic sites within the DWV virion structure enables future analyses of how DWV and other iflaviruses infect insect cells and also opens up possibilities for the development of antiviral treatments.

  11. Airway structure and function in Eisenmenger's syndrome.

    Science.gov (United States)

    McKay, K O; Johnson, P R; Black, J L; Glanville, A R; Armour, C L

    1998-10-01

    The responsiveness of airways from patients with Eisenmenger's syndrome (n = 5) was compared with that in airways from organ donors (n = 10). Enhanced contractile responses to cholinergic stimulation were found in airways from patients with Eisenmenger's syndrome. The maximal responses to acetylcholine, carbachol, and parasympathetic nerve stimulation in airway tissue from these patients were 221%, 139%, and 152%, respectively, of the maximal responses obtained in donor tissue. Further, relaxation responses to isoproterenol and levocromakalim were absent (n = 2) or markedly impaired (n = 3) in airways from patients with Eisenmenger's syndrome. This attenuated relaxation response was nonspecific in that it was also absent after vasoactive intestinal peptide, sodium nitroprusside, papaverine, and electrical field application. These observations can most likely be explained by a decrease in intrinsic smooth muscle tone, as precontraction of airways revealed relaxation responses that were equivalent to those obtained in donor tissues. Morphometric analysis of tissues used for the functional studies revealed no differences in the airway dimensions (internal perimeter) or airway wall components (e.g., smooth muscle, cartilage) or total area to explain these observations. Although the mechanism for this observed decrease in intrinsic airway smooth muscle tone is not certain, it may be due to alteration in the substructure of the airway wall or, alternatively, may result from the continued release of depressant factors in the vicinity of the smooth muscle which permanently alters smooth muscle responsiveness.

  12. Multiple proteins of White spot syndrome virus involved in ...

    Indian Academy of Sciences (India)

    2014-03-20

    Mar 20, 2014 ... β-integrin with structure proteins of WSSV and motifs involved in WSSV infection was examined. The results showed ... Introduction. White spot ... denatured conditions and renatured by successive 12 h incu- bations with 6, 4, ...

  13. Mild Clinical Course of Severe Fever with Thrombocytopenia Syndrome Virus Infection in an Elderly Japanese Patient

    Directory of Open Access Journals (Sweden)

    Yuko Ohagi

    2014-01-01

    Full Text Available Severe fever with thrombocytopenia syndrome (SFTS is an emerging infectious and hemorrhagic disease recently described in China and western Japan. A 71-year-old healthy Japanese woman noticed a tick biting her after harvesting in an orchard and removed it herself. She developed diarrhea, anorexia, and chills eight days later. Because these symptoms continued, she visited a primary care physician 6 days after the onset. Laboratory data revealed thrombocytopenia, leukocytopenia, and elevated liver enzymes. She was then referred to our hospital. Although not completely fulfilling the diagnostic criteria used in a retrospective study in Japan, SFTS was suspected, and we detected SFTS virus in the patient’s blood using RT-PCR. However, she recovered without intensive treatment and severe complications 13 days after the onset. In this report, we present a mild clinical course of SFTS virus infection in Japan in detail.

  14. Spinal cord toxoplasmosis in human immunodeficiency virus infection/acquired immunodeficiency syndrome.

    Science.gov (United States)

    García-García, Concepción; Castillo-Álvarez, Federico; Azcona-Gutiérrez, José M; Herraiz, María J; Ibarra, Valvanera; Oteo, José A

    2015-05-01

    Neurological complications in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) are still common, even in the era of highly active antiretroviral therapy. Opportunistic infections, immune reconstitution, the virus itself, antiretroviral drugs and neurocognitive disorders have to be considered when establishing the differential diagnosis. Toxoplasmic encephalitis remains the major cause of space-occupying lesions in the brain of patients with HIV/AIDS; however, spinal cord involvement has been reported infrequently. Here, we review spinal cord toxoplasmosis in HIV infection and illustrate the condition with a recent case from our hospital. We suggest that most patients with HIV/AIDS and myelitis with enhanced spine lesions, multiple brain lesions and positive serology for Toxoplasma gondii should receive immediate empirical treatment for toxoplasmosis, and a biopsy should be performed in those cases without clinical improvement or with deterioration.

  15. White spot syndrome virus (WSSV) infection in shrimp (Litopenaeus vannamei) exposed to low and high salinity.

    Science.gov (United States)

    Ramos-Carreño, Santiago; Valencia-Yáñez, Ricardo; Correa-Sandoval, Francisco; Ruíz-García, Noé; Díaz-Herrera, Fernando; Giffard-Mena, Ivone

    2014-09-01

    White spot syndrome virus (WSSV) has a worldwide distribution and is considered one of the most pathogenic and devastating viruses to the shrimp industry. A few studies have explored the effect of WSSV on shrimp acclimated to low (5 practical salinity units [psu]) or high ([40 psu) salinity conditions. In this work, we analysed the physiological response of WSSV-infected Litopenaeus vannamei juveniles that were acclimated to different salinities (5, 15, 28, 34 and 54 psu). We evaluated the osmotic response and survival of the shrimp at different times after infection (0 to 48 hours), and we followed the expression levels of a viral gene (vp664) in shrimp haemolymph using real-time PCR. Our results indicate that the susceptibility of the shrimp to the virus increased at extreme salinities (5 and 54 psu), with higher survival rates at 15 and 28 psu, which were closer to the iso-osmotic point (24.7 psu, 727.5 mOsmol/kg). Acute exposure to the virus made the haemolymph less hyperosmotic at 5 and 15 psu and less hypo-osmotic at higher salinities ([28 psu). The capacity of white shrimp to osmoregulate, and thus survive, significantly decreased following WSSV infection. According to our results, extreme salinities (5 or 54 psu) are more harmful than seawater.

  16. Chimeric viruses containing the N-terminal ectodomains of GP5 and M proteins of porcine reproductive and respiratory syndrome do not change the cellular tropism of equine arteritis virus

    Science.gov (United States)

    Equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus (PRRSV) are members of family Arteriviridae; they share many biological properties but differ significantly in cellular tropism. Using an infectious cDNA clone of EAV, we engineered a panel of six chimeric viruses b...

  17. Turner syndrome: neuroimaging findings: structural and functional.

    LENUS (Irish Health Repository)

    Mullaney, Ronan

    2009-01-01

    Neuroimaging studies of Turner syndrome can advance our understanding of the X chromosome in brain development, and the modulatory influence of endocrine factors. There is increasing evidence from neuroimaging studies that TX individuals have significant differences in the anatomy, function, and metabolism of a number of brain regions; including the parietal lobe; cerebellum, amygdala, hippocampus; and basal ganglia; and perhaps differences in "connectivity" between frontal and parieto-occipital regions. Finally, there is preliminary evidence that genomic imprinting, sex hormones and growth hormone have significant modulatory effects on brain maturation in TS.

  18. The Link between Hypersensitivity Syndrome Reaction Development and Human Herpes Virus-6 Reactivation

    Directory of Open Access Journals (Sweden)

    Joshua C. Pritchett

    2012-01-01

    Data Sources and Extraction. Drugs identified as causes of (i idiosyncratic reactions, (ii drug-induced hypersensitivity, drug-induced hepatotoxicity, acute liver failure, and Stevens-Johnson syndrome, and (iii human herpes virus reactivation in PubMed since 1997 have been collected and discussed. Results. Data presented in this paper show that HHV-6 reactivation is associated with more severe organ involvement and a prolonged course of disease. Conclusion. This analysis of HHV-6 reactivation associated with drug-induced severe cutaneous reactions and hepatotoxicity will aid in causality assessment and clinical diagnosis of possible life-threatening events and will provide a basis for further patient characterization and therapy.

  19. Structural transitions in Cowpea chlorotic mottle virus (CCMV)

    Science.gov (United States)

    Liepold, Lars O.; Revis, Jennifer; Allen, Mark; Oltrogge, Luke; Young, Mark; Douglas, Trevor

    2005-12-01

    Viral capsids act as molecular containers for the encapsulation of genomic nucleic acid. These protein cages can also be used as constrained reaction vessels for packaging and entrapment of synthetic cargos. The icosahedral Cowpea chlorotic mottle virus (CCMV) is an excellent model for understanding the encapsulation and packaging of both genomic and synthetic materials. High-resolution structural information of the CCMV capsid has been invaluable for evaluating structure-function relationships in the assembled capsid but does not allow insight into the capsid dynamics. The dynamic nature of the CCMV capsid might play an important role in the biological function of the virus. The CCMV capsid undergoes a pH and metal ion dependent reversible structural transition where 60 separate pores in the capsid open or close, exposing the interior of the protein cage to the bulk medium. In addition, the highly basic N-terminal domain of the capsid, which is disordered in the crystal structure, plays a significant role in packaging the viral cargo. Interestingly, in limited proteolysis and mass spectrometry experiments the N-terminal domain is the first part of the subunit to be cleaved, confirming its dynamic nature. Based on our fundamental understanding of the capsid dynamics in CCMV, we have utilized these aspects to direct packaging of a range of synthetic materials including drugs and inorganic nanoparticles.

  20. Assessing Photoreceptor Structure in Retinitis Pigmentosa and Usher Syndrome.

    Science.gov (United States)

    Sun, Lynn W; Johnson, Ryan D; Langlo, Christopher S; Cooper, Robert F; Razeen, Moataz M; Russillo, Madia C; Dubra, Alfredo; Connor, Thomas B; Han, Dennis P; Pennesi, Mark E; Kay, Christine N; Weinberg, David V; Stepien, Kimberly E; Carroll, Joseph

    2016-05-01

    The purpose of this study was to examine cone photoreceptor structure in retinitis pigmentosa (RP) and Usher syndrome using confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). Nineteen subjects (11 RP, 8 Usher syndrome) underwent ophthalmic and genetic testing, spectral-domain optical coherence tomography (SD-OCT), and AOSLO imaging. Split-detector images obtained in 11 subjects (7 RP, 4 Usher syndrome) were used to assess remnant cone structure in areas of altered cone reflectivity on confocal AOSLO. Despite normal interdigitation zone and ellipsoid zone appearance on OCT, foveal and parafoveal cone densities derived from confocal AOSLO images were significantly lower in Usher syndrome compared with RP. This was due in large part to an increased prevalence of non-waveguiding cones in the Usher syndrome retina. Although significantly correlated to best-corrected visual acuity and foveal sensitivity, cone density can decrease by nearly 38% before visual acuity becomes abnormal. Aberrantly waveguiding cones were noted within the transition zone of all eyes and corresponded to intact inner segment structures. These remnant cones decreased in density and increased in diameter across the transition zone and disappeared with external limiting membrane collapse. Foveal cone density can be decreased in RP and Usher syndrome before visible changes on OCT or a decline in visual function. Thus, AOSLO imaging may allow more sensitive monitoring of disease than current methods. However, confocal AOSLO is limited by dependence on cone waveguiding, whereas split-detector AOSLO offers unambiguous and quantifiable visualization of remnant cone inner segment structure. Confocal and split-detector thus offer complementary insights into retinal pathology.

  1. Live porcine reproductive and respiratory syndrome virus vaccines: Current status and future direction.

    Science.gov (United States)

    Renukaradhya, Gourapura J; Meng, Xiang-Jin; Calvert, Jay G; Roof, Michael; Lager, Kelly M

    2015-08-07

    Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) was reported in the late 1980s. PRRS still is a huge economic concern to the global pig industry with a current annual loss estimated at one billion US dollars in North America alone. It has been 20 years since the first modified live-attenuated PRRSV vaccine (PRRSV-MLV) became commercially available. PRRSV-MLVs provide homologous protection and help in reducing shedding of heterologous viruses, but they do not completely protect pigs against heterologous field strains. There have been many advances in understanding the biology and ecology of PRRSV; however, the complexities of virus-host interaction and PRRSV vaccinology are not yet completely understood leaving a significant gap for improving breadth of immunity against diverse PRRS isolates. This review provides insights on immunization efforts using infectious PRRSV-based vaccines since the 1990s, beginning with live PRRSV immunization, development and commercialization of PRRSV-MLV, and strategies to overcome the deficiencies of PRRSV-MLV through use of replicating viral vectors expressing multiple PRRSV membrane proteins. Finally, powerful reverse genetics systems (infectious cDNA clones) generated from more than 20 PRRSV isolates of both genotypes 1 and 2 viruses have provided a great resource for exploring many innovative strategies to improve the safety and cross-protective efficacy of live PRRSV vaccines. Examples include vaccines with diminished ability to down-regulate the immune system, positive and negative marker vaccines, multivalent vaccines incorporating antigens from other porcine pathogens, vaccines that carry their own cytokine adjuvants, and chimeric vaccine viruses with the potential for broad cross-protection against heterologous strains. To combat this devastating pig disease in the future, evaluation and commercialization of such improved live PRRSV vaccines is a shared goal among PRRSV researchers, pork

  2. Tangential flow ultrafiltration for detection of white spot syndrome virus (WSSV) in shrimp pond water.

    Science.gov (United States)

    Alavandi, S V; Ananda Bharathi, R; Satheesh Kumar, S; Dineshkumar, N; Saravanakumar, C; Joseph Sahaya Rajan, J

    2015-06-15

    Water represents the most important component in the white spot syndrome virus (WSSV) transmission pathway in aquaculture, yet there is very little information. Detection of viruses in water is a challenge, since their counts will often be too low to be detected by available methods such as polymerase chain reaction (PCR). In order to overcome this difficulty, viruses in water have to be concentrated from large volumes of water prior to detection. In this study, a total of 19 water samples from aquaculture ecosystem comprising 3 creeks, 10 shrimp culture ponds, 3 shrimp broodstock tanks and 2 larval rearing tanks of shrimp hatcheries and a sample from a hatchery effluent treatment tank were subjected to concentration of viruses by ultrafiltration (UF) using tangential flow filtration (TFF). Twenty to 100l of water from these sources was concentrated to a final volume of 100mL (200-1000 fold). The efficiency of recovery of WSSV by TFF ranged from 7.5 to 89.61%. WSSV could be successfully detected by PCR in the viral concentrates obtained from water samples of three shrimp culture ponds, one each of the shrimp broodstock tank, larval rearing tank, and the shrimp hatchery effluent treatment tank with WSSV copy numbers ranging from 6 to 157mL(-1) by quantitative real time PCR. The ultrafiltration virus concentration technique enables efficient detection of shrimp viral pathogens in water from aquaculture facilities. It could be used as an important tool to understand the efficacy of biosecurity protocols adopted in the aquaculture facility and to carry out epidemiological investigations of aquatic viral pathogens. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Structural and mechanistic studies of measles virus illuminate paramyxovirus entry.

    Directory of Open Access Journals (Sweden)

    Richard K Plemper

    2011-06-01

    Full Text Available Measles virus (MeV, a member of the paramyxovirus family of enveloped RNA viruses and one of the most infectious viral pathogens identified, accounts for major pediatric morbidity and mortality worldwide although coordinated efforts to achieve global measles control are in place. Target cell entry is mediated by two viral envelope glycoproteins, the attachment (H and fusion (F proteins, which form a complex that achieves merger of the envelope with target cell membranes. Despite continually expanding knowledge of the entry strategies employed by enveloped viruses, our molecular insight into the organization of functional paramyxovirus fusion complexes and the mechanisms by which the receptor binding by the attachment protein triggers the required conformational rearrangements of the fusion protein remain incomplete. Recently reported crystal structures of the MeV attachment protein in complex with its cellular receptors CD46 or SLAM and newly developed functional assays have now illuminated some of the fundamental principles that govern cell entry by this archetype member of the paramyxovirus family. Here, we review these advances in our molecular understanding of MeV entry in the context of diverse entry strategies employed by other members of the paramyxovirus family.

  4. Prevalence and distribution of White Spot Syndrome Virus in cultured shrimp.

    Science.gov (United States)

    Hossain, A; Nandi, S P; Siddique, M A; Sanyal, S K; Sultana, M; Hossain, M A

    2015-02-01

    White Spot Syndrome Virus (WSSV) is a dsDNA virus causing White Spot Syndrome Disease (WSSD) in shrimp with almost 100% morality rate within 3-10 days. In Bangladesh, WSSD is one of the major impediments of shrimp farming. This study first investigated the prevalence and distribution of WSSV in cultured shrimps of the coastal regions in Bangladesh. A total of 60 shrimp samples, collected from the 25 shrimp farms of different coastal regions (Satkhira, Khulna, Bagerhat and Cox's Bazar), were analysed during 2013-2014 by conventional PCR using VP28 and VP664 gene-specific primers; 39 of 60 samples were found WSSV positive. SYBR green real-time PCR using 71-bp amplicon for VP664 gene correlated well with conventional PCR data. The prevalence rates of WSSV among the collected 60 samples were Satkhira 79%, Khulna 50%, Bagerhat 38% and Cox's Bazar 25%. Sequencing of WSSV-positive PCR amplicons of VP28 showed 99% similarity with WSSV NCBI Ref/Seq Sequences. Molecular analysis of the VP28 gene sequences of WSSV revealed that Bangladeshi strains phylogenetically affiliated to the strains belong to India. This work concluded that WSSV infections are widely distributed in the coastal regions cultured shrimp in Bangladesh. © 2014 The Society for Applied Microbiology.

  5. Nucleocapsid-like structures of Ebola virus reconstructed using electron tomography

    International Nuclear Information System (INIS)

    Noda, T.; Aoyama, K.; Sagara, H.; Kida, H.; Kawaoka, Y.

    2005-01-01

    Electron tomography (ET) is a new technique for high resolution, three-dimensional (3D) reconstruction of pleiomocphic mac. n)molecular complexes, such as virus components. By employing this technique, we resolved the 3D structure of Ebola virus nucleocapsid-like (NC-like) structures in the cytoplasm of cells expressing NP, VP24, and VP35: the minimum components required to form these NC-like structures. Reconstruction of these tubular NC-like structures of Ebola virus showed them to be composed of left-handed helices spaced at short intervals, which is structurally consistent with other non-segmented negative-strand RNA viruses

  6. Structural basis of Zika virus helicase in recognizing its substrates

    Directory of Open Access Journals (Sweden)

    Hongliang Tian

    2016-07-01

    Full Text Available Abstract The recent explosive outbreak of Zika virus (ZIKV infection has been reported in South and Central America and the Caribbean. Neonatal microcephaly associated with ZIKV infection has already caused a public health emergency of international concern. No specific vaccines or drugs are currently available to treat ZIKV infection. The ZIKV helicase, which plays a pivotal role in viral RNA replication, is an attractive target for therapy. We determined the crystal structures of ZIKV helicase-ATP-Mn2+ and ZIKV helicase-RNA. This is the first structure of any flavivirus helicase bound to ATP. Comparisons with related flavivirus helicases have shown that although the critical P-loop in the active site has variable conformations among different species, it adopts an identical mode to recognize ATP/Mn2+. The structure of ZIKV helicase-RNA has revealed that upon RNA binding, rotations of the motor domains can cause significant conformational changes. Strikingly, although ZIKV and dengue virus (DENV apo-helicases share conserved residues for RNA binding, their different manners of motor domain rotations result in distinct individual modes for RNA recognition. It suggests that flavivirus helicases could have evolved a conserved engine to convert chemical energy from nucleoside triphosphate to mechanical energy for RNA unwinding, but different motor domain rotations result in variable RNA recognition modes to adapt to individual viral replication.

  7. Zika Virus and Guillain–Barre Syndrome: Is There Sufficient Evidence for Causality?

    Science.gov (United States)

    Leis, A. Arturo; Stokic, Dobrivoje S.

    2016-01-01

    Worldwide concern over Zika virus causing Guillain–Barre syndrome (GBS) soared after recent reports that Zika-related weakness was due to GBS. A global strategic response plan was initiated with recommendations for at-risk countries to prepare for GBS. This plan has major economic implications, as nations with limited resources struggle to implement costly immunotherapy. Since confirmation of causality is prerequisite to providing specific management recommendations, it is prudent to review data endorsing a GBS diagnosis. We searched PubMed for manuscripts reporting original clinical, laboratory, and electrodiagnostic data on Zika virus and GBS. Five papers met criteria; four case reports and one large case–control study (French Polynesia) that attributed 42 paralysis cases to a motor variant of GBS. Brighton criteria were reportedly used to diagnose GBS, but no differential diagnosis was presented, which violates criteria. GBS was characterized by early onset (median 6 days post-viral syndrome), rapid progression (median 6 days from onset to nadir), and atypical clinical features (52% lacked areflexia, 48% of facial palsies were unilateral). Electrodiagnostic evaluations fell short of guidelines endorsed by American Academy of Neurology. Typical anti-ganglioside antibodies in GBS motor variants were rarely present. We conclude that there is no causal relationship between Zika virus and GBS because data failed to confirm GBS and exclude other causes of paralysis. Focus should be redirected at differential diagnosis, proper use of diagnostic criteria, and electrodiagnosis that follows recommended guidelines. We also call for a moratorium on recommendations for at-risk countries to prepare costly immunotherapies directed at GBS. PMID:27746763

  8. Zika Virus and Guillain-Barre Syndrome: Is There Sufficient Evidence for Causality?

    Directory of Open Access Journals (Sweden)

    A Arturo Leis

    2016-09-01

    Full Text Available Worldwide concern over Zika virus causing Guillain-Barre syndrome (GBS soared after recent reports that Zika-related weakness was due to GBS. A global strategic response plan was initiated with recommendations for at risk countries to prepare for GBS. This plan has major economic implications, as nations with limited resources struggle to implement costly immunotherapy. Since confirmation of causality is prerequisite to providing specific management recommendations, it is prudent to review data endorsing a GBS diagnosis. We searched PubMed for manuscripts reporting original clinical, laboratory, and electrodiagnostic data on Zika virus and GBS. Five papers met criteria; four case reports and one large case-control study (French Polynesia that attributed 42 paralysis cases to a motor variant of GBS. Brighton criteria were reportedly used to diagnose GBS, but no differential diagnosis was presented, which violates criteria. GBS was characterized by early onset (median 6 days post-viral syndrome, rapid progression (median 6 days from onset to nadir, and atypical clinical features (52% lacked areflexia, 48% of facial palsies were unilateral. Electrodiagnostic evaluations fell short of guidelines endorsed by American Academy of Neurology. Typical anti-ganglioside antibodies in GBS motor variants were rarely present. We conclude that there is no causal relationship between Zika virus and GBS because data failed to confirm GBS and exclude other causes of paralysis. Focus should be redirected at differential diagnosis, proper use of diagnostic criteria, and electrodiagnosis that follows recommended guidelines. We also call for a moratorium on recommendations for at risk countries to prepare costly immunotherapies directed at GBS.

  9. Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments

    Directory of Open Access Journals (Sweden)

    Bas Verbruggen

    2016-01-01

    Full Text Available Since its emergence in the 1990s, White Spot Disease (WSD has had major economic and societal impact in the crustacean aquaculture sector. Over the years shrimp farming alone has experienced billion dollar losses through WSD. The disease is caused by the White Spot Syndrome Virus (WSSV, a large dsDNA virus and the only member of the Nimaviridae family. Susceptibility to WSSV in a wide range of crustacean hosts makes it a major risk factor in the translocation of live animals and in commodity products. Currently there are no effective treatments for this disease. Understanding the molecular basis of disease processes has contributed significantly to the treatment of many human and animal pathogens, and with a similar aim considerable efforts have been directed towards understanding host–pathogen molecular interactions for WSD. Work on the molecular mechanisms of pathogenesis in aquatic crustaceans has been restricted by a lack of sequenced and annotated genomes for host species. Nevertheless, some of the key host–pathogen interactions have been established: between viral envelope proteins and host cell receptors at initiation of infection, involvement of various immune system pathways in response to WSSV, and the roles of various host and virus miRNAs in mitigation or progression of disease. Despite these advances, many fundamental knowledge gaps remain; for example, the roles of the majority of WSSV proteins are still unknown. In this review we assess current knowledge of how WSSV infects and replicates in its host, and critique strategies for WSD treatment.

  10. Borderline tuberculoid leprosy: A manifestation of immune reconstitution inflammatory syndrome in a human immunodeficiency virus infected person

    Directory of Open Access Journals (Sweden)

    Mukhopadhyay Partha

    2006-01-01

    Full Text Available Immune reconstitution inflammatory syndrome describes a collection of inflammatory disorders associated with paradoxical deterioration of various pre-existing processes following start of highly active antiretroviral therapy (HAART in human immunodeficiency virus (HIV-infected patients. Leprosy as an opportunistic infection in immune reconstitution syndrome has been rarely reported in literature. A case of a 30-year-old HIV positive man with extrapulmonary tuberculosis of left foot on HAART having developed borderline tuberculoid leprosy as opportunistic infection in immune reconstitution syndrome has been reported.

  11. Production of polyclonal antiserum specific to the 27.5 kDa envelope protein of white spot syndrome virus

    NARCIS (Netherlands)

    You, Z.O.; Nadala, E.C.B.; Yang, J.S.; Hulten, van M.C.W.; Loh, P.C.

    2002-01-01

    A truncated version of the white spot syndrome virus (WSSV) 27.5 kDa envelope protein was expressed as a histidine tag fusion protein in Escherichia coli. The bacterial expression system allowed the production of up to 10 mg of purified recombinant protein per liter of bacterial culture. Antiserum

  12. Identification of Stressors that Affect White Spot Syndrome Virus (WSSV) Infection and Outbreak in Pond Cultured Penaeus monodon

    NARCIS (Netherlands)

    Tendencia Alapide, E.; Verreth, J.A.J.

    2011-01-01

    White spot syndrome virus (WSSV) has been a big problem to the worldwide shrimp industry. Exposure to stressors related to physicochemical water parameters affect WSSV infection but not all WSSV infections result in outbreaks. This paper describes a detailed monitoring of important physicochemical

  13. Increased pathogenicity of European porcine reproductive and respiratory syndrome virus is associated with enhanced adaptive responses and viral clearance

    NARCIS (Netherlands)

    Morgan, S.B.; Graham, S.P.; Salguero, F.J.; Sánchez Cordón, P.J.; Mokhtar, H.; Rebel, J.M.J.; Weesendorp, E.; Bodman-Smith, K.B.; Steinbach, F.; Frossard, J.P.

    2013-01-01

    Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important diseases of swine worldwide. Since its first emergence in 1987 the PRRS virus (PRRSV) has become particularly divergent with highly pathogenic strains appearing in both Europe and Asia. However, the

  14. Left ventricular structural and functional characteristics in Cushing's syndrome.

    Science.gov (United States)

    Muiesan, Maria Lorenza; Lupia, Mario; Salvetti, Massimo; Grigoletto, Consuelo; Sonino, Nicoletta; Boscaro, Marco; Rosei, Enrico Agabiti; Mantero, Franco; Fallo, Francesco

    2003-06-18

    This study was designed to evaluate left ventricular (LV) anatomy and function in patients with Cushing's syndrome. A high prevalence of LV hypertrophy and concentric remodeling has been reported in Cushing's syndrome, although no data have been reported on LV systolic and diastolic function. Forty-two consecutive patients with Cushing's syndrome and 42 control subjects, matched for age, gender, and blood pressure, were studied. Left ventricular mass index (LVMI) and relative wall thickness (RWT) were measured by echocardiography, endocardial and midwall fractional shortening (FS) were assessed, and diastolic filling was measured by Doppler transmitral flow. The RWT was significantly greater in Cushing patients than in controls. Left ventricular hypertrophy and concentric remodeling were observed in 10 and 26 patients with Cushing's syndrome, respectively. In Cushing patients, midwall FS was significantly reduced compared with controls (16.2 +/- 3% vs. 21 +/- 4.5%, p = 0.01). The ratio of transmitral E and A flow velocities was reduced and E deceleration time was prolonged in Cushing patients compared with controls (p = 0.03 and p < 0.001, respectively). In patients with Cushing's syndrome, cardiac structural changes are associated with reduced midwall systolic performance and with diastolic dysfunction that may contribute to the high risk of cardiovascular events observed in these patients.

  15. RNA structural constraints in the evolution of the influenza A virus genome NP segment

    NARCIS (Netherlands)

    A.P. Gultyaev (Alexander); A. Tsyganov-Bodounov (Anton); M.I. Spronken (Monique); S. Van Der Kooij (Sander); R.A.M. Fouchier (Ron); R.C.L. Olsthoorn (René)

    2014-01-01

    textabstractConserved RNA secondary structures were predicted in the nucleoprotein (NP) segment of the influenza A virus genome using comparative sequence and structure analysis. A number of structural elements exhibiting nucleotide covariations were identified over the whole segment length,

  16. Genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV)

    DEFF Research Database (Denmark)

    Snow, M.; Bain, N.; Black, J.

    2004-01-01

    The nucleotide sequences of a specific region of the nucleoprotein gene were compared in order to investigate the genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV). Analysis of the sequence from 128 isolates of diverse geographic and host origin renders this the m......The nucleotide sequences of a specific region of the nucleoprotein gene were compared in order to investigate the genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV). Analysis of the sequence from 128 isolates of diverse geographic and host origin renders...... this the most comprehensive molecular epidemiological study of marine VHSV conducted to date. Phylogenetic analysis of nucleoprotein gene sequences confirmed the existence of the 4 major genotypes previously identified based on N- and subsequent G-gene based analyses. The range of Genotype I included subgroups...... of isolates associated with rainbow trout aquaculture (Genotype la) and those from the Baltic marine environment (Genotype Ib) to emphasise the relatively close genetic relationship between these isolates. The existence of an additional genotype circulating within the Baltic Sea (Genotype II) was also...

  17. Hepatitis C Virus E2 Envelope Glycoprotein Core Structure

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Leopold; Giang, Erick; Nieusma, Travis; Kadam, Rameshwar U.; Cogburn, Kristin E.; Hua, Yuanzi; Dai, Xiaoping; Stanfield, Robyn L.; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.; Law, Mansun

    2014-08-26

    Hepatitis C virus (HCV), a Hepacivirus, is a major cause of viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV envelope glycoproteins E1 and E2 mediate fusion and entry into host cells and are the primary targets of the humoral immune response. The crystal structure of the E2 core bound to broadly neutralizing antibody AR3C at 2.65 angstroms reveals a compact architecture composed of a central immunoglobulin-fold β sandwich flanked by two additional protein layers. The CD81 receptor binding site was identified by electron microscopy and site-directed mutagenesis and overlaps with the AR3C epitope. The x-ray and electron microscopy E2 structures differ markedly from predictions of an extended, three-domain, class II fusion protein fold and therefore provide valuable information for HCV drug and vaccine design.

  18. Epstein-Barr virus myelitis and Castleman's disease in a patient with acquired immune deficiency syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Balderacchi Jasminka

    2011-05-01

    Full Text Available Abstract Introduction Few cases of Epstein-Barr virus myelitis have been described in the literature. Multi-centric Castleman's disease is a lymphoproliferative disorder that is well known for its associations with the human immunodeficiency virus, human herpes virus 8, and Kaposi's sarcoma. The concurrent presentation of these two diseases in a patient at the same time is extremely unusual. Case Presentation We describe the case of a 43-year-old Caucasian man with acquired immune deficiency syndrome who presented with fever, weight loss and diffuse lymphadenopathy, and was diagnosed with multi-centric Castleman's disease. He presented three weeks later with lower extremity weakness and urinary retention, at which time cerebrospinal fluid contained lymphocytic pleocytosis and elevated protein. Magnetic resonance imaging demonstrated abnormal spinal cord signal intensity over several cervical and thoracic segments, suggesting the diagnosis of myelitis. Our patient was ultimately diagnosed with Epstein-Barr virus myelitis, as Epstein-Barr virus DNA was detected by polymerase chain reaction in the cerebrospinal fluid. Conclusion To the best of our knowledge, this is the first case of multi-centric Castleman's disease followed by acute Epstein-Barr virus myelitis in a human immunodeficiency virus-infected patient. Clinicians caring for human immunodeficiency virus-infected patients should be vigilant about monitoring patients with increasing lymphadenopathy, prompting thorough diagnostic investigations when necessary.

  19. Cleft analysis of Zika virus non-structural protein 1

    Institute of Scientific and Technical Information of China (English)

    Somsri Wiwanitkit; Viroj Wiwanitkit

    2017-01-01

    The non-strctural protein 1 is an important molecule of the viruses in flavivirus group including to Zika virus. Recently, the NS1 of Zika virus was discovered.There is still no complete information of the molecular interaction of NS1 of Zika virus which can be the clue for explanation for its pathogenesis and further drug search. Here the authors report the cleft analysis of NS1 of Zika virus and the result can be useful for future development of good diagnostic tool and antiviral drug finding for management of Zika virus.

  20. Structural and Functional Motifs in Influenza Virus RNAs

    Directory of Open Access Journals (Sweden)

    Damien Ferhadian

    2018-03-01

    Full Text Available Influenza A viruses (IAV are responsible for recurrent influenza epidemics and occasional devastating pandemics in humans and animals. They belong to the Orthomyxoviridae family and their genome consists of eight (- sense viral RNA (vRNA segments of different lengths coding for at least 11 viral proteins. A heterotrimeric polymerase complex is bound to the promoter consisting of the 13 5′-terminal and 12 3′-terminal nucleotides of each vRNA, while internal parts of the vRNAs are associated with multiple copies of the viral nucleoprotein (NP, thus forming ribonucleoproteins (vRNP. Transcription and replication of vRNAs result in viral mRNAs (vmRNAs and complementary RNAs (cRNAs, respectively. Complementary RNAs are the exact positive copies of vRNAs; they also form ribonucleoproteins (cRNPs and are intermediate templates in the vRNA amplification process. On the contrary, vmRNAs have a 5′ cap snatched from cellular mRNAs and a 3′ polyA tail, both gained by the viral polymerase complex. Hence, unlike vRNAs and cRNAs, vmRNAs do not have a terminal promoter able to recruit the viral polymerase. Furthermore, synthesis of at least two viral proteins requires vmRNA splicing. Except for extensive analysis of the viral promoter structure and function and a few, mostly bioinformatics, studies addressing the vRNA and vmRNA structure, structural studies of the influenza A vRNAs, cRNAs, and vmRNAs are still in their infancy. The recent crystal structures of the influenza polymerase heterotrimeric complex drastically improved our understanding of the replication and transcription processes. The vRNA structure has been mainly studied in vitro using RNA probing, but its structure has been very recently studied within native vRNPs using crosslinking and RNA probing coupled to next generation RNA sequencing. Concerning vmRNAs, most studies focused on the segment M and NS splice sites and several structures initially predicted by bioinformatics analysis

  1. Probing of RNA structures in a positive sense RNA virus reveals selection pressures for structural elements

    Science.gov (United States)

    Watters, Kyle E; Choudhary, Krishna; Aviran, Sharon; Perry, Keith L

    2018-01-01

    Abstract In single stranded (+)-sense RNA viruses, RNA structural elements (SEs) play essential roles in the infection process from replication to encapsidation. Using selective 2′-hydroxyl acylation analyzed by primer extension sequencing (SHAPE-Seq) and covariation analysis, we explore the structural features of the third genome segment of cucumber mosaic virus (CMV), RNA3 (2216 nt), both in vitro and in plant cell lysates. Comparing SHAPE-Seq and covariation analysis results revealed multiple SEs in the coat protein open reading frame and 3′ untranslated region. Four of these SEs were mutated and serially passaged in Nicotiana tabacum plants to identify biologically selected changes to the original mutated sequences. After passaging, loop mutants showed partial reversion to their wild-type sequence and SEs that were structurally disrupted by mutations were restored to wild-type-like structures via synonymous mutations in planta. These results support the existence and selection of virus open reading frame SEs in the host organism and provide a framework for further studies on the role of RNA structure in viral infection. Additionally, this work demonstrates the applicability of high-throughput chemical probing in plant cell lysates and presents a new method for calculating SHAPE reactivities from overlapping reverse transcriptase priming sites. PMID:29294088

  2. Polarisation of Major Histocompatibility Complex II Host Genotype with Pathogenesis of European Brown Hare Syndrome Virus

    DEFF Research Database (Denmark)

    Iacovakis, Christos; Mamuris, Zissis; Moutou, Katerina A

    2013-01-01

    A study was conducted in order to determine the occurrence of European Brown Hare Syndrome virus (EBHSV) in Denmark and possible relation between disease pathogenesis and Major Histocompatibility Complex (MHC) host genotype. Liver samples were examined from 170 brown hares (hunted, found sick...... were found to be EBHSV-positive (RT-PCR, VP60 gene). In order to investigate associations between viral pathogenesis and host genotype, variation within the exon 2 DQA gene of MHC was assessed. DQA exon 2 analysis revealed the occurrence of seven different alleles in Denmark. Consistent with other...... populations examined so far in Europe, observed heterozygosity of DQA (H o = 0.1180) was lower than expected (H e = 0.5835). The overall variation for both nucleotide and amino acid differences (2.9% and 14.9%, respectively) were lower in Denmark than those assessed in other European countries (8.3% and 16...

  3. Low-dose growth hormone and human immunodeficiency virus-associated lipodystrophy syndrome: a pilot study

    DEFF Research Database (Denmark)

    Andersen, Ove; Haugaard, Steen B; Flyvbjerg, A

    2004-01-01

    BACKGROUND: Treatment with high doses (2-6 mg day(-1)) of human growth hormone (hGH) in patients with human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) has been shown to increase concentrations of total insulin-like growth-factor-I (IGF-I) more than twofold greater than......-I and fat distribution. Glucose metabolism was examined by oral glucose tolerance tests and hyperinsulinaemic euglycaemic clamps. RESULTS: Total IGF-I increased twofold (P ....01). Patients reported improvements of lipodystrophy, which was supported by a decreased waist-to-thigh ratio (P = 0.01), and waist-to-hip ratio (P = 0.06). Ratio of peripheral to trunk soft tissue mass increased (P = 0.01, measured by dual-energy X-ray absorptiometry scans) and a trend towards reduction...

  4. Genotyping of white spot syndrome virus on wild and farm crustaceans from Sonora, Mexico

    Directory of Open Access Journals (Sweden)

    González-Galaviz José Reyes

    2013-01-01

    Full Text Available White spot syndrome is a viral disease affecting wild and farm crustaceans that serve as reservoirs. Previous reports have demonstrated high genomic variation in WSS viruses (WSSV isolated from distinct geographical regions. In this study, we collected wild shrimps (Litopenaeus stylirostris, crabs (Callinectes arcuatus and farmed shrimp (L. vannamei in Sonora, Mexico, between 2008 and 2010. DNA was extracted, and the variable regions and transposase genes were subjected to PCR and sequencing. Compared to strains of WSSV from other sites, Mexican samples exhibited a distinct number of repeat units (RUs in ORF94, ORF75 and ORF125, which ranged between 1-11, 3-15, and 8-11 RUs respectively, and a unique single nucleotide polymorphism (SNP at position 48 of ORF94. A total of six Mexican genotypes were found in organism from shrimp farm and natural environment.

  5. [A double antibody sandwich ELISA based assay for titration of severe fever with thrombocytopenia syndrome virus].

    Science.gov (United States)

    Liu, Lin; Zhang, Quan-Fu; Li, Chuan; Li, Jian-Dong; Jiang, Xiao-Lin; Zhang, Fu-Shun; Wu, Wei; Liang, Mi-Fang; Li, De-Xin

    2013-06-01

    To develop an assay for titration of severe fever with thrombocytopenia syndrome virus (SFTSV) based on double antibody sandwich ELISA. A double antibody sandwich ELISA was developed for detection of SFTSV based on SFTSV nucleocapsid (N) protein specific poly- and monoclonal antibodies, procedures were optimized and evaluated. This ELISA based titration assay was compared with fluorescence assasy and plaque assay based titration method. The results suggested that the titers obtained by ELISA based method are consistent with those obtained by IFA based method (R = 0.999) and the plaque assay titration method (R = 0.949). The novel ELISA based titration method with high sensitivity and specificity is easy to manage and perform, and can overcome the subjectivity associated with result determination of the fluorescence assay and plaque assay based methods. The novel ELISA based titration method can also be applied to high throughput detection.

  6. Molecular detection of severe fever with thrombocytopenia syndrome virus (SFTSV) in feral cats from Seoul, Korea.

    Science.gov (United States)

    Hwang, Jusun; Kang, Jun-Gu; Oh, Sung-Suck; Chae, Jeong-Byoung; Cho, Yun-Kyung; Cho, Young-Sun; Lee, Hang; Chae, Joon-Seok

    2017-01-01

    This study tested serum samples of feral cats from a highly urbanized habitat, Seoul, Korea to determine the infection to severe fever with thrombocytopenia syndrome virus (SFTSV). From 126 samples tested, SFTSV was detected by RT-PCR in 22 (17.5%) cats from various sites of Seoul. Sequences identified from this study were grouped with clusters from China and Japan. Our result provides data that SFTSV may have been circulating in settings that were suspected to have relatively low risk, such as highly urbanized habitats. Thus it warrants further study to investigate the ecology of SFTSV in urban-dwelling animals including ticks, human and other potential host species. Copyright © 2016 Elsevier GmbH. All rights reserved.

  7. Isolation and identification of porcine reproductive and respiratory syndrome virus in cell cultures.

    Science.gov (United States)

    Valícek, L; Psikal, I; Smíd, B; Rodák, L; Kubalíková, R; Kosinová, E

    1997-10-01

    Three strains of porcine reproductive and respiratory syndrome virus (PRRSV) were isolated in porcine lung macrophage (PLM) cultures from three swine herds. This has been the first successful isolation of PRRSV in the Czech Republic and the strains received the designations CAPM V-501, CAPM V-502 and CAPM V-503, respectively. All the three isolates in PLM were identified by immunofluorescence and immunoperoxidase tests and the strain CAPM V-502 also by electron microscopy using the ultrathin section technique. The strain CAPM V-502 has been adapted to the cell line MARC-145. Viral RNA in PLM cultures infected with any of the isolated PRRSV strains was demonstrated by RT-PCR targeted to the more conserved ORF 7 genomic region encoding the nucleocapsid protein. The assessment of PCR products in agarose gel revealed a uniform size of 394 bp in all the three isolates and the European prototype strain Lelystad used as positive control.

  8. Functional identification of the non-specific nuclease from white spot syndrome virus

    International Nuclear Information System (INIS)

    Li Li; Lin Shumei; Yanga Feng

    2005-01-01

    The product encoded by the wsv191 gene from shrimp white spot syndrome virus (WSSV) is homologous with non-specific nucleases (NSN) of other organisms. To functionally identify the protein, the wsv191 gene was expressed in Escherichia coli as a glutathione S-transferase (GST) fusion protein with 6His-tag at C-terminal. The fusion protein (termed as rWSSV-NSN) was purified using Ni-NTA affinity chromatography under denatured conditions, renatured and characterized by three methods. The results showed that rWSSV-NSN could hydrolyze both DNA and RNA. 5'-RACE result revealed that the transcription initiation site of the wsv191 gene was located at nucleotide residue G of the predicted ATG triplet. Therefore, we concluded that the next ATG should be the genuine translation initiation codon of the wsv191 gene. Western blot analysis revealed that the molecular mass of natural WSSV-NSN was 37 kDa

  9. The effects of a thermophile metabolite, tryptophol, upon protecting shrimp against white spot syndrome virus.

    Science.gov (United States)

    Zhu, Fei; Jin, Min

    2015-12-01

    White spot syndrome virus (WSSV) is a shrimp pathogen responsible for significant economic loss in commercial shrimp farms and until now, there has been no effective approach to control this disease. In this study, tryptophol (indole-3-ethanol) was identified as a metabolite involved in bacteriophage-thermophile interactions. The dietary addition of tryptophol reduced the mortality in shrimp Marsupenaeus japonicus when orally challenged with WSSV. Our results revealed that 50 mg/kg tryptophol has a better protective effect in shrimp than 10 or 100 mg/kg tryptophol. WSSV copies in shrimp were reduced significantly (P shrimp, and thus holds significant promise as a novel and efficient therapeutic approach to control WSSV in shrimp aquaculture. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Expression, purification and crystallization of two major envelope proteins from white spot syndrome virus

    International Nuclear Information System (INIS)

    Tang, Xuhua; Hew, Choy Leong

    2007-01-01

    The crystallization of the N-terminal transmembrane region-truncated VP26 and VP28 of white spot syndrome virus is described. White spot syndrome virus (WSSV) is a major virulent pathogen known to infect penaeid shrimp and other crustaceans. VP26 and VP28, two major envelope proteins from WSSV, have been identified and overexpressed in Escherichia coli. In order to facilitate purification and crystallization, predicted N-terminal transmembrane regions of approximately 35 amino acids have been truncated from both VP26 and VP28. Truncated VP26 and VP28 and their corresponding SeMet-labelled proteins were purified and the SeMet proteins were crystallized by the hanging-drop vapour-diffusion method. Crystals of SeMet-labelled VP26 were obtained using a reservoir consisting of 0.1 M citric acid pH 3.5, 3.0 M sodium chloride and 1%(w/v) polyethylene glycol 3350, whereas SeMet VP28 was crystallized using a reservoir solution consisting of 25% polyethylene glycol 8000, 0.2 M calcium acetate, 0.1 M Na HEPES pH 7.5 and 1.5%(w/v) 1,2,3-heptanetriol. Crystals of SeMet-labelled VP26 diffract to 2.2 Å resolution and belong to space group R32, with unit-cell parameters a = b = 73.92, c = 199.31 Å. SeMet-labelled VP28 crystallizes in space group P2 1 2 1 2 1 , with unit-cell parameters a = 105.33, b = 106.71, c = 200.37 Å, and diffracts to 2.0 Å resolution

  11. Expression, purification and crystallization of two major envelope proteins from white spot syndrome virus

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Xuhua; Hew, Choy Leong, E-mail: dbshewcl@nus.edu.sg [Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543 (Singapore)

    2007-07-01

    The crystallization of the N-terminal transmembrane region-truncated VP26 and VP28 of white spot syndrome virus is described. White spot syndrome virus (WSSV) is a major virulent pathogen known to infect penaeid shrimp and other crustaceans. VP26 and VP28, two major envelope proteins from WSSV, have been identified and overexpressed in Escherichia coli. In order to facilitate purification and crystallization, predicted N-terminal transmembrane regions of approximately 35 amino acids have been truncated from both VP26 and VP28. Truncated VP26 and VP28 and their corresponding SeMet-labelled proteins were purified and the SeMet proteins were crystallized by the hanging-drop vapour-diffusion method. Crystals of SeMet-labelled VP26 were obtained using a reservoir consisting of 0.1 M citric acid pH 3.5, 3.0 M sodium chloride and 1%(w/v) polyethylene glycol 3350, whereas SeMet VP28 was crystallized using a reservoir solution consisting of 25% polyethylene glycol 8000, 0.2 M calcium acetate, 0.1 M Na HEPES pH 7.5 and 1.5%(w/v) 1,2,3-heptanetriol. Crystals of SeMet-labelled VP26 diffract to 2.2 Å resolution and belong to space group R32, with unit-cell parameters a = b = 73.92, c = 199.31 Å. SeMet-labelled VP28 crystallizes in space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 105.33, b = 106.71, c = 200.37 Å, and diffracts to 2.0 Å resolution.

  12. Characterization of Nora Virus Structural Proteins via Western Blot Analysis.

    Science.gov (United States)

    Ericson, Brad L; Carlson, Darby J; Carlson, Kimberly A

    2016-01-01

    Nora virus is a single stranded RNA picorna-like virus with four open reading frames (ORFs). The coding potentials of the ORFs are not fully characterized, but ORF3 and ORF4 are believed to encode the capsid proteins (VP3, VP4a, VP4b, and VP4c) comprising the virion. To determine the polypeptide composition of Nora virus virions, polypeptides from purified virus were compared to polypeptides detected in Nora virus infected Drosophila melanogaster. Nora virus was purified from infected flies and used to challenge mice for the production of antisera. ORF3, ORF4a, ORF4b, and ORF4c were individually cloned and expressed in E. coli; resultant recombinant proteins purified and were used to make monospecific antisera. Antisera were evaluated via Western blot against whole virus particles and Nora virus infected fly lysates. Viral purification yielded two particle types with densities of ~1.31 g/mL (empty particles) and ~1.33 g/mL (complete virions). Comparison of purified virus polypeptide composition to Nora virus infected D. melanogaster lysate showed the number of proteins in infected cell lysates is less than purified virus. Our results suggest the virion is composed of 6 polypeptides, VP3, VP4a, two forms of VP4b, and two forms of VP4c. This polypeptide composition is similar to other small RNA insect viruses.

  13. Crystal structure of the Japanese encephalitis virus envelope protein.

    Science.gov (United States)

    Luca, Vincent C; AbiMansour, Jad; Nelson, Christopher A; Fremont, Daved H

    2012-02-01

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

  14. Characterization of polyclonal antibodies against nonstructural protein 9 from the porcine reproductive and respiratory syndrome virus

    Directory of Open Access Journals (Sweden)

    Mengmeng ZHAO,Juanjuan QIAN,Jiexiong XIE,Tiantian CUI,Songling FENG,Guoqiang WANG,Ruining WANG,Guihong ZHANG

    2016-06-01

    Full Text Available Porcine reproductive and respiratory syndrome (PRRS is considered to be one of the most important infectious diseases impacting the swine industry and is characterized by reproductive failure in late term gestation in sows and respiratory disease in pigs of all ages. The nonstructural protein 9 gene, Nsp9, encoding the RNA-dependent RNA polymerase, is generally regarded as fairly conserved when compared to other viral proteins. Antibodies against Nsp9 will be of great importance for the diagnosis and treatment of the causal agent, PRRS virus. A study was undertaken to generate polyclonal antibodies against the immunodominant Nsp9. For this purpose, the Nsp9 was expressed in Escherichia coli and subsequently used as an antigen to immunize New Zealand rabbits. Antiserum was identified via an indirect ELISA, and then verified based on the ability to react with both naturally and artificially expressed Nsp9. Results of virus neutralization test showed that this antiserum could not neutralize the PRRSV. Nevertheless, this antiserum as a diagnostic core reagent should prove invaluable for further investigations into the mechanism of PRRS pathogenesis.

  15. Prevalence of severe fever with thrombocytopenia syndrome virus in Haemaphysalis longicornis ticks in South Korea.

    Science.gov (United States)

    Park, Sun-Whan; Song, Bong Gu; Shin, E-Hyun; Yun, Seok-Min; Han, Myung-Guk; Park, Mi Yeoun; Park, Chan; Ryou, Jungsang

    2014-10-01

    Haemaphysalis longicornis a vector that harbors severe fever with thrombocytopenia syndrome virus (SFTSV) is a major species of tick in South Korea. To investigate the existence and prevalence of SFTSV in Korea, we collected ticks from nine provinces in South Korea for detecting SFTSV. In all, we collected 13,053 ticks, and H. longicornis (90.8%, 11,856/13,053) was the most abundant among them. The minimum infection rate (MIR) of SFTSV in H. longicornis was 0.46% (55 pools). SFTSV was detected in ticks during all the developmental stages, showing MIR in larvae (2/350, 0.57%), nymphs (38/10,436, 0.36%), males (2/221, 0.90%), and females (13/849, 1.53%), respectively. Viruses were detected in ticks collected between April and September. A higher MIR was detected in ticks from the southern part of the country. We amplified the M and S segment partial genes from a sample and analyzed the nucleotide sequence. The results showed a 93-98% homology to Chinese and Japanese strains registered in Genbank. In this study, we confirmed the existence of SFTSV for the first time in South Korea. The SFTSV prevalence data from the studies are essential for raising the awareness of SFTS in South Korea. Copyright © 2014 Elsevier GmbH. All rights reserved.

  16. Down syndrome as risk factor for respiratory syncytial virus hospitalization: A prospective multicenter epidemiological study.

    Science.gov (United States)

    Sánchez-Luna, Manuel; Medrano, Constancio; Lirio, Julián

    2017-03-01

    Respiratory syncytial virus (RSV) infection in childhood, particularly in premature infants, is associated with significant morbidity and mortality. To compare the hospitalization rates due to RSV infection and severity of disease between infants with and without Down syndrome (DS) born at term and without other associated risk factors for severe RSV infection. In a prospective multicentre epidemiological study, 93 infants were included in the DS cohort and 68 matched by sex and data of birth (±1 week) and were followed up to 1 year of age and during a complete RSV season. The hospitalization rate for all acute respiratory infection was significantly higher in the DS cohort than in the non-DS cohort (44.1% vs 7.7%, P<.0001). Hospitalizations due to RSV were significantly more frequent in the DH cohort than in the non-DS cohort (9.7% vs 1.5%, P=.03). RSV prophylaxis was recorded in 33 (35.5%) infants with DS. The rate of hospitalization according to presence or absence of RSV immunoprophylaxis was 3.0% vs 15%, respectively. Infants with DS showed a higher rate of hospitalization due to acute lower respiratory tract infection and RSV infection compared to non-DS infants. Including DS infants in recommendations for immunoprophylaxis of RSV disease should be considered. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  17. Recent insights into host-pathogen interaction in white spot syndrome virus infected penaeid shrimp.

    Science.gov (United States)

    Shekhar, M S; Ponniah, A G

    2015-07-01

    Viral disease outbreaks are a major concern impeding the development of the shrimp aquaculture industry. The viral disease due to white spot syndrome virus (WSSV) observed in early 1990s still continues unabated affecting the shrimp farms and cause huge economic loss to the shrimp aquaculture industry. In the absence of effective therapeutics to control WSSV, it is important to understand viral pathogenesis and shrimp response to WSSV at the molecular level. Identification and molecular characterization of WSSV proteins and receptors may facilitate in designing and development of novel therapeutics and antiviral drugs that may inhibit viral replication. Investigations into host-pathogen interactions might give new insights to viral infectivity, tissue tropism and defence mechanism elicited in response to WSSV infection. However, due to the limited information on WSSV gene function and host immune response, the signalling pathways which are associated in shrimp pathogen interaction have also not been elucidated completely. In the present review, the focus is on those shrimp proteins and receptors that are potentially involved in virus infection or in the defence mechanism against WSSV. In addition, the major signalling pathways involved in the innate immune response and the role of apoptosis in host-pathogen interaction is discussed. © 2014 John Wiley & Sons Ltd.

  18. Transmission of white spot syndrome virus (WSSV) from Dendronereis spp. (Peters) (Nereididae) to penaeid shrimp.

    Science.gov (United States)

    Haryadi, D; Verreth, J A J; Verdegem, M C J; Vlak, J M

    2015-05-01

    Dendronereis spp. (Peters) (Nereididae) is a common polychaete in shrimp ponds built on intertidal land and is natural food for shrimp in traditionally managed ponds in Indonesia. White spot syndrome virus (WSSV), an important viral pathogen of the shrimp, can replicate in this polychaete (Desrina et al. 2013); therefore, it is a potential propagative vector for virus transmission. The major aim of this study was to determine whether WSSV can be transmitted from naturally infected Dendronereis spp. to specific pathogen-free (SPF) Pacific white shrimp Litopenaeus vannamei (Boone) through feeding. WSSV was detected in naturally infected Dendronereis spp. and Penaeus monodon Fabricius from a traditional shrimp pond, and the positive animals were used in the current experiment. WSSV-infected Dendronereis spp. and P. monodon in a pond had a point prevalence of 90% and 80%, respectively, as measured by PCR. WSSV was detected in the head, gills, blood and mid-body of Dendronereis spp. WSSV from naturally infected Dendronereis spp was transmitted to SPF L. vannamei and subsequently from this shrimp to new naïve-SPF L. vannamei to cause transient infection. Our findings support the contention that Dendronereis spp, upon feeding, can be a source of WSSV infection of shrimp in ponds. © 2014 John Wiley & Sons Ltd.

  19. Associated Factors for Metabolic Syndrome in the Older Adults with Chronic Virus Hepatitis in the Community.

    Directory of Open Access Journals (Sweden)

    Yuan-Hung Kuo

    Full Text Available This study was to evaluate the association between metabolic syndrome (MetS and chronic virus hepatitis elders in the community. Those subjects with positive hepatitis B surface antigen (HBsAg and/or anti-hepatitis C virus (anti-HCV screened in the community before were invited to this study and 451 responded. All participants underwent anthropometric measurements, blood tests, ultrasound and fibroscan examinations. The cut-off of liver stiffness measurement-liver cirrhosis (LSM-LC was 10 kPa for chronic hepatitis B (CHB patients and 12 kPa for chronic hepatitis C (CHC patients, respectively. Among 451 responders, 56 were excluded due to negative HBsAg or anti-HCV. Three hundreds and ninety-five subjects included 228 CHB patients, 156 CHC patients and 11 dual hepatitis patients, had a mean age of 62±12.6 years. Fifty-four (23.7% CHB patients coexisted with MetS whereas 40 (25.6% CHC patients also had MetS. Those patients with MetS had more LSM-LC cases than those without (20.4% vs 9.8%, p = 0.04 in CHB patients; 28.2% vs 13.5%, p = 0.037 in CHC patients, respectively. In multivariate logistic analysis, detectable viremia was reversely associated with MetS in CHB patients after adjustment for age, gender and body mass index (odds ratio (OR: 0.42; 95% confidence interval (CI: 0.18-0.99; p = 0.047. Regarding CHC patients, higher LSM level was the only factor contributed to MetS (OR: 1.1; 95% CI: 1.02-1.19; p = 0.012. In conclusion, elder CHB patients coexisted with MetS might experience an inactive virus replication but have an advanced liver fibrosis. In elder CHC patients, only higher LSM level was associated with MetS.

  20. Guillain–Barré Syndrome (42 Cases) Occurring During a Zika Virus Outbreak in French Polynesia

    Science.gov (United States)

    Watrin, Louise; Ghawché, Frédéric; Larre, Philippe; Neau, Jean-Philippe; Mathis, Stéphane; Fournier, Emmanuel

    2016-01-01

    Abstract Zika virus (transmitted by mosquitoes) reached French Polynesia for the first time in 2013, leading to an epidemic affecting 10% of the total population. So far, it has not been known to induce any neurological complications, but, a few weeks after the outbreak, an unexpectedly high number of 42 patients presented with Guillain–Barré syndrome. We report the clinical and electrophysiological characteristics of this series. Males predominated with a sex ratio of 2.82 (mean age: 46). All patients (except 2) were native Polynesian. At admission, 55% were able to walk unaided against 38% at nadir, 24% had swallowing troubles (nadir: 45%), 74% had motor weakness of the limbs (nadir: 86%) and deep tendon reflexes were diminished or not found in the vast majority of patients. Mean duration of the progressive phase and of the plateau phase was respectively 7 and 9 days. Thirty-eight percent of the patients were admitted in intensive care unit and 10 patients underwent tracheotomy. Nerve electrophysiological studies at admission showed marked distal motor conduction alterations, which had almost completely disappeared at the 4th month; this pattern was more suggestive of acute motor axonal neuropathy (AMAN) than of acute inflammatory demyelinating polyneuropathy (AIDP). Lumbar puncture showed elevated proteins in 90% of the cases, with cell count always inferior to 50/μL. This epidemic raises several questions, such as the potential existence of interactions between Zika virus and Polynesian HLA system and/or the consequences of several recombination events of this virus. This situation should call for increased vigilance, especially in countries where Aedes mosquitoes are present. PMID:27057874

  1. Guillain-Barré Syndrome (42 Cases) Occurring During a Zika Virus Outbreak in French Polynesia.

    Science.gov (United States)

    Watrin, Louise; Ghawché, Frédéric; Larre, Philippe; Neau, Jean-Philippe; Mathis, Stéphane; Fournier, Emmanuel

    2016-04-01

    Zika virus (transmitted by mosquitoes) reached French Polynesia for the first time in 2013, leading to an epidemic affecting 10% of the total population. So far, it has not been known to induce any neurological complications, but, a few weeks after the outbreak, an unexpectedly high number of 42 patients presented with Guillain-Barré syndrome.We report the clinical and electrophysiological characteristics of this series. Males predominated with a sex ratio of 2.82 (mean age: 46). All patients (except 2) were native Polynesian. At admission, 55% were able to walk unaided against 38% at nadir, 24% had swallowing troubles (nadir: 45%), 74% had motor weakness of the limbs (nadir: 86%) and deep tendon reflexes were diminished or not found in the vast majority of patients. Mean duration of the progressive phase and of the plateau phase was respectively 7 and 9 days. Thirty-eight percent of the patients were admitted in intensive care unit and 10 patients underwent tracheotomy. Nerve electrophysiological studies at admission showed marked distal motor conduction alterations, which had almost completely disappeared at the 4th month; this pattern was more suggestive of acute motor axonal neuropathy (AMAN) than of acute inflammatory demyelinating polyneuropathy (AIDP). Lumbar puncture showed elevated proteins in 90% of the cases, with cell count always inferior to 50/μL.This epidemic raises several questions, such as the potential existence of interactions between Zika virus and Polynesian HLA system and/or the consequences of several recombination events of this virus. This situation should call for increased vigilance, especially in countries where Aedes mosquitoes are present.

  2. Tropism and infectivity of duck-derived egg drop syndrome virus in chickens.

    Directory of Open Access Journals (Sweden)

    Min Kang

    Full Text Available Egg drop syndrome virus (EDSV can markedly decrease egg production in laying hens. Duck is the natural host of EDSV. EDSV derived from ducks abrogate egg drop in laying hens. We have previously confirmed that duck-derived EDSVs have a variety of replication activities in chick embryo liver (CEL cells. However, it is currently unclear whether duck-derived EDSV could display tropism and adaptation in laying hens. This study assessed whether duck-derived EDSV can adapt to laying hens, and estimated the inducing factors. Complete genome sequences of duck-derived EDSVs (D11-JW-012, D11-JW-017, and D11-JW-032 isolates with various replication efficiency in CEL cells and C10-GY-001 isolate causing disease in laying hens were analyzed to find their differences. Phylogenetic analysis of complete genome sequence revealed that C10-GY-001, D11-JW-032, and strain 127 virus as vaccine were clustered into the same group, with D11-JW-012 and D11-JW-017 clustered in another group. Comparison between D11-JW-012 isolate that poorly replicated and D11-JW-017 isolate that replicated well in CEL cells in same cluster revealed six amino acid differences on IVa2, DNA polymerase, endopeptidase, and DNA-binding protein. These amino acids might be key candidates enhancing cellular tropism in chicken. When the pathogenicities of these isolates in laying hens were compared, D11-JW-032 showed severe signs similar to 127 virus, D11-JW-017 showed intermediate signs, while D11-JW-012 showed almost no sign. Eleven amino acids differed between D11-JW-032 and D11-JW-017, and 17 amino acids were different between D11-JW-032 and D11-JW-012. These results suggest that EDSVs derived from ducks have various pathogenicities in laying hens. Key amino acid candidates might have altered their affinity to tropism of laying hens, causing difference pathogenicities.

  3. Virus del dengue: estructura y ciclo viral Dengue virus: structure and viral cycle

    Directory of Open Access Journals (Sweden)

    Myriam L Velandia

    2011-03-01

    Full Text Available El virus del dengue (DENV es el agente causal de la enfermedad conocida como dengue, que es la principal enfermedad viral transmitida por artrópodos en el mundo. El DENV es un flavivirus que ingresa por endocitosis y se replica en el citoplasma de la célula infectada, originando tres proteínas estructurales y siete proteínas no estructurales, sobre las cuales se conocen sólo algunas de sus funciones en la replicación viral o en la infección. El ciclo viral que ocurre en las células infectadas hasta ahora está comenzando a aclararse y su conocimiento permitirá en el futuro próximo diseñar racionalmente moléculas que lo intervengan y eviten la replicación del virus. Durante la infección, el individuo puede presentar fiebre indiferenciada o, en otros casos, puede presentar un proceso generalizado de activación de la respuesta inmunitaria innata y adquirida, lo cual provoca la liberación de factores inflamatorios solubles que alteran la fisiología de los tejidos, principalmente el endotelio, conllevando al desarrollo de manifestaciones clínicas graves. Aunque se ha identificado un gran número de factores del individuo asociados al desarrollo de la enfermedad por DENV, queda por identificar el papel de las diferentes proteínas virales en la patogenia de la enfermedad. En la presente revisión, se presenta una breve actualización sobre la estructura y biología del DENV, de su ciclo viral intracelular y, finalmente, se introducen algunos conceptos sobre la inmunopatogenia de la enfermedad producida por este agente.Dengue virus (DENV is responsible for the clinical entity known as dengue that is a great concern for economy and public health of tropical countries. This flavivirus is a single strand RNA virus that after their translation and replication in host cells produces three structural and seven non-structural proteins with specific function in replication or cell binding process that we will describe here. Intracellular

  4. Tunnel current through virus particles between columnar structures in mesoporous silicon

    Energy Technology Data Exchange (ETDEWEB)

    Vashpanov, Yuriy; Jung, Jae-Il; Dal Kwack, Kae [Electrical Engineering and Computer Science Division of Hanyang Institute of Technology, Hanyang University, 17 Haengdang-dong, Seongdong-gu, 133-791 Seoul (Korea, Republic of)

    2011-07-15

    Earlier we reported on a tunnel charge transport mechanism in mesoporous silicon with columnar structures under adsorption of plant nematode-transmitted polyhedral (NEPO) viruses at room temperature. Additional experiments are performed in this paper to establish that this observed tunnel current is connected to a conduction path through virus particles. The plant NEPO viruses have an orbicular shape with a diameter of around 25-30 nm. This size is matched well to the porous size distribution in manufactured samples. The tunnel charge transport in semiconductor structures was not observed on loading protein macromolecules of smaller sizes. A physical mechanism of the observed phenomena can be interpreted to be the result of a shunting effect through virus particles between the two closely located columnar silicon structures. This effect is likely to result from double points at virus adsorption under the condition of matching of pore and virus sizes. The magnitudes of the tunnel barrier heights depend on the type of loaded plant viruses. The investigated columnar structures of mesoporous silicon can be used for research on the electrical properties of different viruses with corresponding sizes in the range of 20-30 nm. The existence of a tunnel current between columnar structures in mesoporous silicon under virus adsorption can be used as a simple method for their detection in the environment. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  5. Gradual development of the interferon-γ response of swine to porcine reproductive and respiratory syndrome virus infection or vaccination

    International Nuclear Information System (INIS)

    Meier, William A.; Galeota, Judy; Osorio, Fernando A.; Husmann, Robert J.; Schnitzlein, William M.; Zuckermann, Federico A.

    2003-01-01

    Infection of swine with virulent porcine reproductive and respiratory syndrome (PRRS) virus induced a rapid, robust antibody response that comprised predominantly nonneutralizing antibodies and waned after approximately 3 months. In contrast, the initial onset of virus-specific interferon (IFN)-γ-secreting cells (SC) in the pig lymphocyte population remained at a fairly low level during this period and then increased gradually in frequency, plateauing at 6 months postinfection. A similar polarization of the host humoral and cellular immune responses was also observed in pigs immunized with a PRRS-modified live virus (MLV) vaccine. Even coadministration of an adjuvant that enhanced the immune response to a pseudorabies (PR) MLV vaccine failed to alter the induction of PRRS virus-specific IFN-γ SC (comprising predominately CD4/CD8α double positive memory T cells with a minority being typical CD4 - /CD8αβ + T cells) and the generation of neutralizing antibodies. Moreover, unlike inactivated PR virus, nonviable PRRS virus did not elicit virus-neutralizing antibody production. Presumably, an intrinsic property of this pathogen delays the development of the host IFN-γ response and preferentially stimulates the synthesis of antibodies incapable of neutralization

  6. Rapid increase of near atomic resolution virus capsid structures determined by cryo-electron microscopy.

    Science.gov (United States)

    Ho, Phuong T; Reddy, Vijay S

    2018-01-01

    The recent technological advances in electron microscopes, detectors, as well as image processing and reconstruction software have brought single particle cryo-electron microscopy (cryo-EM) into prominence for determining structures of bio-molecules at near atomic resolution. This has been particularly true for virus capsids, ribosomes, and other large assemblies, which have been the ideal specimens for structural studies by cryo-EM approaches. An analysis of time series metadata of virus structures on the methods of structure determination, resolution of the structures, and size of the virus particles revealed a rapid increase in the virus structures determined by cryo-EM at near atomic resolution since 2010. In addition, the data highlight the median resolution (∼3.0 Å) and size (∼310.0 Å in diameter) of the virus particles determined by X-ray crystallography while no such limits exist for cryo-EM structures, which have a median diameter of 508 Å. Notably, cryo-EM virus structures in the last four years have a median resolution of 3.9 Å. Taken together with minimal sample requirements, not needing diffraction quality crystals, and being able to achieve similar resolutions of the crystal structures makes cryo-EM the method of choice for current and future virus capsid structure determinations. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Evaluation of an immunodot test to manage white spot syndrome virus (WSSV) during cultivation of the giant tiger shrimp Penaeus monodon

    Digital Repository Service at National Institute of Oceanography (India)

    Patil, R.; Palaksha, K.J.; Anil, T.M.; Guruchannabasavanna; Patil, P.; Shankar, K.M.; Mohan, C.V.; Sreepada, R.A.

    A monoclonal antibody-based immunodot test was compared to a polymerase chain reaction (PCR) assay for managing white spot syndrome virus (WSSV) on shrimp farms at Kundapur and Kumta situated in Udupi and Uttar Kannada Districts, respectively...

  8. QTL for white spot syndrome virus resistance and the sex-determining locus in the Indian black tiger shrimp (Penaeus monodon).

    Science.gov (United States)

    Robinson, Nicholas A; Gopikrishna, Gopalapillay; Baranski, Matthew; Katneni, Vinaya Kumar; Shekhar, Mudagandur S; Shanmugakarthik, Jayakani; Jothivel, Sarangapani; Gopal, Chavali; Ravichandran, Pitchaiyappan; Gitterle, Thomas; Ponniah, Alphis G

    2014-08-28

    Shrimp culture is a fast growing aquaculture sector, but in recent years there has been a shift away from tiger shrimp Penaeus monodon to other species. This is largely due to the susceptibility of P. monodon to white spot syndrome virus disease (Whispovirus sp.) which has impacted production around the world. As female penaeid shrimp grow more rapidly than males, mono-sex production would be advantageous, however little is known about genes controlling or markers associated with sex determination in shrimp. In this study, a mapped set of 3959 transcribed single nucleotide polymorphisms were used to scan the P. monodon genome for loci associated with resistance to white-spot syndrome virus and sex in seven full-sibling tiger shrimp families challenged with white spot syndrome virus. Linkage groups 2, 3, 5, 6, 17, 18, 19, 22, 27 and 43 were found to contain quantitative trait loci significantly associated with hours of survival after white spot syndrome virus infection (P shrimp.

  9. Comparison of a commercial ELISA and an immunoperoxidase monolayer assay to detect antibodies directed against porcine respiratory and reproductive syndrome virus

    NARCIS (Netherlands)

    Nodelijk, G.; Wensvoort, G.; Kroese, B.; Leengoed, van L.A.M.G.; Colijn, E.; Verheijden, J.H.M.

    1996-01-01

    A commercially available enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against porcine respiratory and reproductive syndrome virus (PRRSV) was compared to an immunoperoxidase monolayer assay (IPMA). Serum samples used were collected from pigs experimentally infected with

  10. Avian Influenza: Potential Impact on Sub-Saharan Military Populations with High Rates of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

    National Research Council Canada - National Science Library

    Feldman, Robert L; Nickell, Kent

    2007-01-01

    ...)/acquired immunodeficiency syndrome. With the arrival of avian influenza in Africa, the potential exists that some of those soldiers might also become infected with H5N1, the virus responsible for the disease...

  11. Clinical characteristics of abnormal savda syndrome type in human immunodeficiency virus infection and acquired immune deficiency syndrome patients: A cross-sectional investigation in Xinjiang, China.

    Science.gov (United States)

    Peierdun, Mi-ji-ti; Liu, Wen-xian; Renaguli, Ai-ze-zi; Nurmuhammat, Amat; Li, Xiao-chun; Gulibaier, Ka-ha-er; Ainivaer, Wu-la-mu; Halmurat, Upur

    2015-12-01

    To investigate the distribution of abnormal hilit syndromes in traditional Uighur medicine (TUM) among human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) patients, and to find out the clinical characteristics of abnormal savda syndrome type HIV/AIDS patients. Between June and July in 2012, 307 eligible HIV/AIDS patients from in-patient department and out-patient clinics of Xinjiang Uighur Autonomous Region the Sixth People's Hospital in Urumqi were investigated. TUM syndrome differentiation was performed by a senior TUM physician. Each participant completed a Sign and Symptom Check-List for Persons Living with HIV/AIDS (SSC-HIV) questionnaire. Depression was evaluated by using Hamilton Rating Scale for Depression Questionnaire. Blood specimen was collected from each participant to test the levels of blood chemicals. Of 307 HIV/AIDS patients, 189 (61.6%) were abnormal savda syndrome type, 118 (38.4%) were non-abnormal-savda syndrome type. Mean CD4 counts of abnormal savda syndrome type patients was (227.61±192.93) cells/µL, and the prevalence of anemia, thrombocytopenia, and elevated cystatin C were 49.7%, 28.6%, and 44.7%, which were significantly higher than those in the non-abnormal-savda syndrome type patients (26.3%, 16.0% and 25.0%,PHIV/AIDS-related symptoms such as fatigue (42.3%), back aches (40.7%), lack of appetite (33.9%), night sweats (31.7%) were more common among abnormal savda syndrome patients (PHIV/AIDS patients, and they present a more sever clinical manifestation.

  12. Localization of VP28 on the baculovirus envelope and its immunogenicity against white spot syndrome virus in Penaeus monodon

    International Nuclear Information System (INIS)

    Syed Musthaq, S.; Madhan, Selvaraj; Sahul Hameed, A.S.; Kwang, Jimmy

    2009-01-01

    White spot syndrome virus (WSSV) is a large dsDNA virus responsible for white spot disease in shrimp and other crustaceans. VP28 is one of the major envelope proteins of WSSV and plays a crucial role in viral infection. In an effort to develop a vaccine against WSSV, we have constructed a recombinant baculovirus with an immediate early promoter 1 which expresses VP28 at an early stage of infection in insect cells. Baculovirus expressed rVP28 was able to maintain its structural and antigenic conformity as indicated by immunofluorescence assay and western blot analysis. Interestingly, our results with confocal microscopy revealed that rVP28 was able to localize on the plasma membrane of insect cells infected with recombinant baculovirus. In addition, we demonstrated with transmission electron microscopy that baculovirus successfully acquired rVP28 from the insect cell membrane via the budding process. Using this baculovirus displaying VP28 as a vaccine against WSSV, we observed a significantly higher survival rate of 86.3% and 73.5% of WSSV-infected shrimp at 3 and 15 days post vaccination respectively. Quantitative real-time PCR also indicated that the WSSV viral load in vaccinated shrimp was significantly reduced at 7 days post challenge. Furthermore, our RT-PCR and immunohistochemistry results demonstrated that the recombinant baculovirus was able to express VP28 in vivo in shrimp tissues. This study will be of considerable significance in elucidating the morphogenesis of WSSV and will pave the way for new generation vaccines against WSSV.

  13. Histologic Changes Associated With Placental Separation in Gilts Infected with Porcine Reproductive and Respiratory Syndrome Virus.

    Science.gov (United States)

    Novakovic, Predrag; Detmer, Susan E; Suleman, Muhammad; Malgarin, Carol M; MacPhee, Daniel J; Harding, John C S

    2018-07-01

    The placenta is a vital organ providing the developing fetus with nutrient and gas exchange, thermoregulation, and waste elimination necessary for fetal development, as well as producing hormones to maintain pregnancy. It is hypothesized that fetal pig death in porcine reproductive and respiratory syndrome may be attributed to pathology of the maternal-fetal interface leading to premature placental separation. This study was designed to evaluate the chronologic progression of porcine reproductive and respiratory syndrome virus (PRRSV)-induced lesions at the maternal-fetal interface, with particular focus on placental separation in experimentally challenged third-trimester gilts. Fifteen gilts were inoculated with a virulent strain of PRRSV-2 on gestation day 86 ± 0.4. On multiple days postinoculation, 3 gilts along with 1 sham-inoculated control per time point were euthanized, and uterine and fetal placental tissues corresponding to each fetus were collected for histopathologic evaluation. The presence of any fetal lesion was 23 times more likely in compromised (meconium-stained and decomposed) compared with viable fetuses ( P < .001). In PRRSV-infected gilts, endometritis was more severe than placentitis, and the severity of endometrial inflammation and vasculitis increased progressively from 2 to 14 days postinoculation. Neither placental vasculitis nor a chronologic progression in the severity of placental detachment was observed. Severe placental detachment was more frequently present in PRRSV-infected compared with noninfected samples and was most significantly associated with placental inflammation, compared with other uterine lesions, viral load, or termination day. The results of this study suggest that placental separation by itself is not sufficient to significantly compromise fetal viability in reproductive porcine reproductive and respiratory syndrome.

  14. A fatal case of middle east respiratory syndrome corona virus infection in South Korea: Cheat radiography and CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Eun; Kim, Hyo Lim; Choi, Su Mi [Dept. of Internal Medicine, Yeouido St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2016-06-15

    The outbreak of Middle East Respiratory Syndrome Corona Virus (MERS-CoV) infection in South Korea originated from Saudi Arabia. This virus shows high infectivity, and causes outbreaks of severe febrile respiratory infections in health care-associated settings. Herein, we reported a fatal case of MERS-CoV infection with a focus on the pulmonary radiologic findings. The initial chest computed tomography and radiographs of our patient showed ground-glass opacity in patchy distribution, followed by rapid progression of consolidation and pleural effusion in serial studies.

  15. Gastric and Peritoneal Involvement of Human Herpes Virus 8 Related Kaposi Sarcoma in a Patient with Acquired Immunodeficiency Syndrome

    Directory of Open Access Journals (Sweden)

    Nuno Ribeiro Ferreira

    2015-09-01

    Full Text Available Kaposi's sarcoma (KS is one of the most frequent neoplastic diseases in patients infected with human immunodeficiency virus (HIV. The authors report the case of a 40-year-old male with ascites, peripheral edema and peritoneal carcinomatosis secondary to a gastric KS related to human herpes virus type 8 (HHV-8. The patient had severe immunodeficiency, with a TCD4+ count of 86 cells/µl and newly diagnosed acquired immunodeficiency syndrome. His clinical condition rapidly deteriorated, with multiorgan failure, and he died without the possibility of initiating antiretroviral therapy or chemotherapy. To the authors’ knowledge, carcinomatosis is a rare feature in KS.

  16. A fatal case of middle east respiratory syndrome corona virus infection in South Korea: Cheat radiography and CT findings

    International Nuclear Information System (INIS)

    Lee, Seung Eun; Kim, Hyo Lim; Choi, Su Mi

    2016-01-01

    The outbreak of Middle East Respiratory Syndrome Corona Virus (MERS-CoV) infection in South Korea originated from Saudi Arabia. This virus shows high infectivity, and causes outbreaks of severe febrile respiratory infections in health care-associated settings. Herein, we reported a fatal case of MERS-CoV infection with a focus on the pulmonary radiologic findings. The initial chest computed tomography and radiographs of our patient showed ground-glass opacity in patchy distribution, followed by rapid progression of consolidation and pleural effusion in serial studies

  17. PREPARATION OF CONJUGATE FOR USE IN AN ELISA FOR HUMORAL IMMUNE RESPONSE AGAINST EGG DROP SYNDROME VIRUS IN LAYER CHICKS

    Directory of Open Access Journals (Sweden)

    M. K. Mansoor, S. U. Rahman, I. Hussain, M. H. Rasool and M. A. Zahoor

    2004-10-01

    Full Text Available An indirect enzyme-linked immunosorbent assay (ELISA was performed for the detection of antibodies against Egg Drop Syndrome (EDS virus. Virus identification was done through haemaggluti- nation inhibition (HI test using known antisera. Antichicken immunoglobulins were raised in goats and purified by ammonium sulphate precipitation technique. These goat-antichicken immunoglobulins were conjugated with horseradish peroxidase. Twenty-seven serum samples were collected from a layers flock vaccinated against EDS and specific antibodies were determined by using a horseradish conjugate.

  18. Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis and Guillain-Barre Syndrome in a 16-Month-Old Child

    Directory of Open Access Journals (Sweden)

    Motohiro Matsui MD

    2016-03-01

    Full Text Available A 16-month-old girl was diagnosed with Epstein-Barr virus hemophagocytic lymphohistiocytosis and transferred to our hospital on the 58th day of the hemophagocytic lymphohistiocytosis after treatment failure according to the Hemophagocytic Lymphohistiocytosis-2004 protocol. On admission to our hospital, she had a flaccid paralysis of her lower limbs. Nerve conduction studies showed a acute motor axonal neuropathy, and a diagnosis of Guillain-Barre syndrome was established. Intravenous immunoglobulin G was started on the 57th day of the Guillain-Barre syndrome. To date, her neurological recovery is incomplete. For hemophagocytic lymphohistiocytosis, after treatment failure of THP-COP regimen (pirarubicin, cyclophosphamide, vincristine, and prednisone and 2 courses of ESCAP regimen (etoposide, prednisone, cytarabine, L-asparaginase, we are now in the process of coordinating unrelated umbilical cord blood transplantation. To the best of our knowledge, we report the youngest case of Guillain-Barre syndrome accompanied by Epstein-Barr virus hemophagocytic lymphohistiocytosis. Rapid progression of Guillain-Barre syndrome, the electrophysiological subtype of Guillain-Barre syndrome, and treatment delay possibly led to poor neurological outcome.

  19. Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis and Guillain-Barre Syndrome in a 16-Month-Old Child.

    Science.gov (United States)

    Matsui, Motohiro; Shimizu, Mariko; Ioi, Aya; Mayumi, Azusa; Higuchi, Kohei; Sawada, Akihisa; Sato, Maho; Yasui, Masahiro; Yanagihara, Keiko; Inoue, Masami

    2016-01-01

    A 16-month-old girl was diagnosed with Epstein-Barr virus hemophagocytic lymphohistiocytosis and transferred to our hospital on the 58th day of the hemophagocytic lymphohistiocytosis after treatment failure according to the Hemophagocytic Lymphohistiocytosis-2004 protocol. On admission to our hospital, she had a flaccid paralysis of her lower limbs. Nerve conduction studies showed a acute motor axonal neuropathy, and a diagnosis of Guillain-Barre syndrome was established. Intravenous immunoglobulin G was started on the 57th day of the Guillain-Barre syndrome. To date, her neurological recovery is incomplete. For hemophagocytic lymphohistiocytosis, after treatment failure of THP-COP regimen (pirarubicin, cyclophosphamide, vincristine, and prednisone) and 2 courses of ESCAP regimen (etoposide, prednisone, cytarabine, L-asparaginase), we are now in the process of coordinating unrelated umbilical cord blood transplantation. To the best of our knowledge, we report the youngest case of Guillain-Barre syndrome accompanied by Epstein-Barr virus hemophagocytic lymphohistiocytosis. Rapid progression of Guillain-Barre syndrome, the electrophysiological subtype of Guillain-Barre syndrome, and treatment delay possibly led to poor neurological outcome.

  20. Angiographic Features and Cardiovascular Risk Factors in Human Immunodeficiency Virus-Infected Patients With First-Time Acute Coronary Syndrome

    DEFF Research Database (Denmark)

    Knudsen, Andreas; Mathiasen, Anders B; Worck, R.H.

    2013-01-01

    A matched cohort study was conducted comparing patients with first-time acute coronary syndromes infected with human immunodeficiency virus (HIV) to non-HIV-infected patients with and without diabetes matched for smoking, gender, and type of acute coronary syndrome who underwent first-time coronary...... angiography. A total of 48 HIV-infected patients were identified from a national database. Coronary angiography showed that the HIV-infected patients had significantly fewer lesions with classification B2/C than the 2 control groups (p...

  1. Epstein-Barr virus-associated adult respiratory distress syndrome in a patient with AIDS: a case report and review

    DEFF Research Database (Denmark)

    Stopyra, G A; Multhaupt, H A; Alexa, L

    1999-01-01

    BACKGROUND: Epstein-Barr virus (EBV) infection has been associated with fatal pneumonitis in immunocompetent patients. We present a case of fatal adult respiratory distress syndrome caused by EBV infection in a patient with acquired immunodeficiency syndrome (AIDS), to our knowledge the first....... RESULTS: Strikingly numerous lymphocytes were positive for EBV early RNA in the case patient's spleen, lymph nodes, and hepatic portal areas. In addition to positive lymphocytes in the lung, EBV-infected pneumocytes were also present. Electron microscopy also demonstrated viral material in lymphocytes...

  2. Structural basis for the antibody neutralization of Herpes simplex virus

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Cheng-Chung; Lin, Li-Ling [Academia Sinica, Taipei 115, Taiwan (China); Academia Sinica, Taipei 115, Taiwan (China); Chan, Woan-Eng [Development Center for Biotechnology, New Taipei City 221, Taiwan (China); Ko, Tzu-Ping [Academia Sinica, Taipei 115, Taiwan (China); Academia Sinica, Taipei 115, Taiwan (China); Lai, Jiann-Shiun [Development Center for Biotechnology, New Taipei City 221, Taiwan (China); Ministry of Economic Affairs, Taipei 100, Taiwan (China); Wang, Andrew H.-J., E-mail: ahjwang@gate.sinica.edu.tw [Academia Sinica, Taipei 115, Taiwan (China); Academia Sinica, Taipei 115, Taiwan (China); Taipei Medical University, Taipei 110, Taiwan (China)

    2013-10-01

    The gD–E317-Fab complex crystal revealed the conformational epitope of human mAb E317 on HSV gD, providing a molecular basis for understanding the viral neutralization mechanism. Glycoprotein D (gD) of Herpes simplex virus (HSV) binds to a host cell surface receptor, which is required to trigger membrane fusion for virion entry into the host cell. gD has become a validated anti-HSV target for therapeutic antibody development. The highly inhibitory human monoclonal antibody E317 (mAb E317) was previously raised against HSV gD for viral neutralization. To understand the structural basis of antibody neutralization, crystals of the gD ectodomain bound to the E317 Fab domain were obtained. The structure of the complex reveals that E317 interacts with gD mainly through the heavy chain, which covers a large area for epitope recognition on gD, with a flexible N-terminal and C-terminal conformation. The epitope core structure maps to the external surface of gD, corresponding to the binding sites of two receptors, herpesvirus entry mediator (HVEM) and nectin-1, which mediate HSV infection. E317 directly recognizes the gD–nectin-1 interface and occludes the HVEM contact site of gD to block its binding to either receptor. The binding of E317 to gD also prohibits the formation of the N-terminal hairpin of gD for HVEM recognition. The major E317-binding site on gD overlaps with either the nectin-1-binding residues or the neutralizing antigenic sites identified thus far (Tyr38, Asp215, Arg222 and Phe223). The epitopes of gD for E317 binding are highly conserved between two types of human herpesvirus (HSV-1 and HSV-2). This study enables the virus-neutralizing epitopes to be correlated with the receptor-binding regions. The results further strengthen the previously demonstrated therapeutic and diagnostic potential of the E317 antibody.

  3. Severe fever with thrombocytopenia syndrome virus inhibits exogenous Type I IFN signaling pathway through its NSs invitro.

    Science.gov (United States)

    Chen, Xu; Ye, Haiyan; Li, Shilin; Jiao, Baihai; Wu, Jianqin; Zeng, Peibin; Chen, Limin

    2017-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus (SFTS virus, SFTSV). At present there is still no specific antiviral treatment for SFTSV; To understand which cells support SFTSV life cycle and whether SFTSV infection activates host innate immunity, four different cell lines (Vero, Hela, Huh7.5.1, and Huh7.0) were infected with SFTSV. Intracellular/extracellular viral RNA and expression of IFNα, and IFNß were detected by real-time RT- PCR following infection. To confirm the role of non-structural protein (NSs) of SFTSV in exogenous IFNα-induced Jak/STAT signaling, p-STAT1 (Western Blot), ISRE activity (Luciferase assay) and ISG expression (real-time PCR) were examined following IFNα stimulation in the presence or absence of over-expression of NSs in Hela cells. Our study showed that all the four cell lines supported SFTSV life cycle and SFTSV activated host innate immunity to produce type I IFNs in Hela cells but not in Huh7.0, Huh7.5.1 or Vero cells. NSs inhibited exogenous IFNα-induced Jak/STAT signaling as shown by decreased p-STAT1 level, suppressed ISRE activity and down-regulated ISG expression. Suppression of the exogenous Type I IFN-induced Jak/STAT signaling by NSs might be one of the mechanisms of SFTSV to evade host immune surveillance.

  4. Chemical constituents from Chirita longgangensis var. hongyao with inhibitory activity against porcine respiratory and reproductive syndrome virus

    Energy Technology Data Exchange (ETDEWEB)

    Su, Yao; Wang, Yue-Hu; Tan, Ying; Yang, Jun; Liu, Hong-Xin; Gu, Wei; Long, Chun-Lin, E-mail: long@mail.kib.ac.cn [Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences (China); Bi, Jun-Long; Yin, Ge-Fen, E-mail: yingefen383@sohu.com [College of Animal Science and Technology, Yunnan Agricultural University (China)

    2012-10-15

    Two new quinonoids chiritalone A and B, and a new neolignan 7'E-4,9-dihydroxy- 3,3',5'-trimethoxy-8,4'-oxyneolign-7'-en-9'-al, along with known (-)-8-hydroxy-{alpha}-dunnione, digiferruginol, 2,5-dimethoxy-1,4-benzoquinone and hederagenin, were isolated from the stems of Chirita longgangensis var. hongyao. The structures of the new compounds were elucidated by detailed analysis from NMR (nuclear magnetic resonance) and MS (mass spectrometry) data, and the absolute configuration of chiritalone A was determined by single crystal X-ray diffraction analysis using the Flack parameter. The inhibitory activity of compounds against porcine respiratory and reproductive syndrome virus (PRRSV) was measured by the cytopathic effect (CPE) method. Digiferruginol and hederagenin showed weak effect on PRRSV with an IC{sub 50} value of 80.5 {+-} 16.9 {mu}mol L{sup -1} (SI = 19.9) and 43.2 {+-} 7.4 {mu}mol L{sup -1} (SI = 13.1), respectively. (author)

  5. Chemical constituents from Chirita longgangensis var. hongyao with inhibitory activity against porcine respiratory and reproductive syndrome virus

    International Nuclear Information System (INIS)

    Su, Yao; Wang, Yue-Hu; Tan, Ying; Yang, Jun; Liu, Hong-Xin; Gu, Wei; Long, Chun-Lin; Bi, Jun-Long; Yin, Ge-Fen

    2012-01-01

    Two new quinonoids chiritalone A and B, and a new neolignan 7'E-4,9-dihydroxy- 3,3',5'-trimethoxy-8,4'-oxyneolign-7'-en-9'-al, along with known (-)-8-hydroxy-α-dunnione, digiferruginol, 2,5-dimethoxy-1,4-benzoquinone and hederagenin, were isolated from the stems of Chirita longgangensis var. hongyao. The structures of the new compounds were elucidated by detailed analysis from NMR (nuclear magnetic resonance) and MS (mass spectrometry) data, and the absolute configuration of chiritalone A was determined by single crystal X-ray diffraction analysis using the Flack parameter. The inhibitory activity of compounds against porcine respiratory and reproductive syndrome virus (PRRSV) was measured by the cytopathic effect (CPE) method. Digiferruginol and hederagenin showed weak effect on PRRSV with an IC 50 value of 80.5 ± 16.9 μmol L -1 (SI = 19.9) and 43.2 ± 7.4 μmol L -1 (SI = 13.1), respectively. (author)

  6. Viruses in the marine environment: community dynamics, phage-host interactions and genomic structure

    OpenAIRE

    Lara de la Casa, Elena

    2014-01-01

    There are an estimated 1030 viruses in the world oceans, the majority of which are phages (viruses that infect bacteria). Extensive research has demonstrated the significant influence of marine phages on microbial abundance, community structure, genetic exchange and global biogeochemical cycles. In this thesis, we contribute to increase the knowledge about the ecological role of viruses in marine systems, but also we aimed to provide a better understanding about the interactions between phage...

  7. Structural constraints in the packaging of bluetongue virus genomic segments.

    Science.gov (United States)

    Burkhardt, Christiane; Sung, Po-Yu; Celma, Cristina C; Roy, Polly

    2014-10-01

    The mechanism used by bluetongue virus (BTV) to ensure the sorting and packaging of its 10 genomic segments is still poorly understood. In this study, we investigated the packaging constraints for two BTV genomic segments from two different serotypes. Segment 4 (S4) of BTV serotype 9 was mutated sequentially and packaging of mutant ssRNAs was investigated by two newly developed RNA packaging assay systems, one in vivo and the other in vitro. Modelling of the mutated ssRNA followed by biochemical data analysis suggested that a conformational motif formed by interaction of the 5' and 3' ends of the molecule was necessary and sufficient for packaging. A similar structural signal was also identified in S8 of BTV serotype 1. Furthermore, the same conformational analysis of secondary structures for positive-sense ssRNAs was used to generate a chimeric segment that maintained the putative packaging motif but contained unrelated internal sequences. This chimeric segment was packaged successfully, confirming that the motif identified directs the correct packaging of the segment. © 2014 The Authors.

  8. Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection.

    Science.gov (United States)

    Berenguer, Juan; Rodríguez-Castellano, Elena; Carrero, Ana; Von Wichmann, Miguel A; Montero, Marta; Galindo, María J; Mallolas, Josep; Crespo, Manuel; Téllez, María J; Quereda, Carmen; Sanz, José; Barros, Carlos; Tural, Cristina; Santos, Ignacio; Pulido, Federico; Guardiola, Josep M; Rubio, Rafael; Ortega, Enrique; Montes, María L; Jusdado, Juan J; Gaspar, Gabriel; Esteban, Herminia; Bellón, José M; González-García, Juan

    2017-08-01

    We assessed non-liver-related non-acquired immunodeficiency syndrome (AIDS)-related (NLR-NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk. The NLR-NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR-NAR cancer, bone events, and non-AIDS-related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4 + T-cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti-HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5-year follow-up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35-0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17-1.09; P = 0.075). Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver-related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344-356). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

  9. Entry of porcine reproductive and respiratory syndrome virus into porcine alveolar macrophages via receptor-mediated endocytosis.

    Science.gov (United States)

    Nauwynck, H J; Duan, X; Favoreel, H W; Van Oostveldt, P; Pensaert, M B

    1999-02-01

    Porcine alveolar macrophages (AMphi) are the dominant cell type that supports the replication of porcine reproductive and respiratory syndrome virus (PRRSV) in vivo and in vitro. In order to determine the characteristics of the virus-receptor interaction, the attachment of PRRSV to cells was examined by using biotinylated virus in a series of flow cytometric assays. PRRSV bound specifically to AMphi in a dose-dependent manner. Binding of PRRSV to AMphi increased gradually and reached a maximum within 60 min at 4 degrees C. By confocal microscopy, it was shown that different degrees of PRRSV binding exist and that entry is by endocytosis. Virus uptake in vesicles is a clathrin-dependent process, as it was blocked by the addition of cytochalasin D and co-localization of PRRSV and clathrin was found. Furthermore, by the use of two weak bases, NH4Cl and chloroquine, it was demonstrated that PRRSV uses a low pH-dependent entry pathway. In the presence of these reagents, input virions accumulated in large vacuoles, indicating that uncoating was prevented. These results indicate that PRRSV entry into AMphi involves attachment to a specific virus receptor(s) followed by a process of endocytosis, by which virions are taken into the cell within vesicles by a clathrin-dependent pathway. A subsequent drop in pH is required for proper virus replication.

  10. Serological survey of severe fever with thrombocytopenia syndrome virus infection in Sika deer and rodents in Japan

    OpenAIRE

    Lundu, Tapiwa; Yoshii, Kentaro; Kobayashi, Shintaro; Morikawa, Shigeru; Tsubota, Toshio; Misawa, Naoaki; Hayasaka, Daisuke; Kariwa, Hiroaki

    2018-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is a newly recognized zoonosis that occurs in China, Japan, and South Korea and is caused by the SFTS virus (SFTSV), which is in the genus Phlebovirus, family Phenuiviridae. Since its discovery in Japan in 2013, SFTS has been reported in the western parts of the country. To elucidate the distribution of SFTSV, we conducted a serological survey of deer and rodents. Serum was screened using enzyme-linked immunosorbent assay (ELISA) and suspecte...

  11. Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome

    Energy Technology Data Exchange (ETDEWEB)

    DeFreitas, E.; Hilliard, B.; Cheney, P.R.; Bell, D.S.; Kiggundu, E.; Sankey, D.; Wroblewska, Z.; Palladino, M.; Woodward, J.P.; Koprowski, H. (Wistar Inst., Philadelphia, PA (United States))

    1991-04-01

    Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but unknown etiology. The authors evaluted 30 adult and pediatric CFIDS patients from six eastern states for the presence of human T-lymphotropic virus (HTLV) types I and II by Western immunoblotting, polymerase chain reaction, and in situ hybridization of blood samples. The majority of patients were positive for HTLV antibodies by Western blotting and for HTLV-II gag sequences by polymerase chain reaction and in situ hybridization. Twenty nonexposure healthy controls were negative in all assays. These data support an association between an HTLV-II-like virus and CFIDS.

  12. Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome

    International Nuclear Information System (INIS)

    DeFreitas, E.; Hilliard, B.; Cheney, P.R.; Bell, D.S.; Kiggundu, E.; Sankey, D.; Wroblewska, Z.; Palladino, M.; Woodward, J.P.; Koprowski, H.

    1991-01-01

    Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but unknown etiology. The authors evaluted 30 adult and pediatric CFIDS patients from six eastern states for the presence of human T-lymphotropic virus (HTLV) types I and II by Western immunoblotting, polymerase chain reaction, and in situ hybridization of blood samples. The majority of patients were positive for HTLV antibodies by Western blotting and for HTLV-II gag sequences by polymerase chain reaction and in situ hybridization. Twenty nonexposure healthy controls were negative in all assays. These data support an association between an HTLV-II-like virus and CFIDS

  13. Antigenic structure of the capsid protein of rabbit haemorrhagic disease virus

    DEFF Research Database (Denmark)

    Martinez-Torrecuadrada, Jorge L.; Cortes, Elena; Vela, Carmen

    1998-01-01

    Rabbit haemorrhagic disease virus (RHDV) causes an important disease in rabbits. The virus capsid is composed of a single 60 kDa protein. The capsid protein gene was cloned in Escherichia coli using the pET3 system, and the antigenic structure of RHDV VP60 was dissected using 11 monoclonal...

  14. Structural dissection of Ebola virus and its assembly determinants using cryo-electron tomography.

    Science.gov (United States)

    Bharat, Tanmay A M; Noda, Takeshi; Riches, James D; Kraehling, Verena; Kolesnikova, Larissa; Becker, Stephan; Kawaoka, Yoshihiro; Briggs, John A G

    2012-03-13

    Ebola virus is a highly pathogenic filovirus causing severe hemorrhagic fever with high mortality rates. It assembles heterogenous, filamentous, enveloped virus particles containing a negative-sense, single-stranded RNA genome packaged within a helical nucleocapsid (NC). We have used cryo-electron microscopy and tomography to visualize Ebola virus particles, as well as Ebola virus-like particles, in three dimensions in a near-native state. The NC within the virion forms a left-handed helix with an inner nucleoprotein layer decorated with protruding arms composed of VP24 and VP35. A comparison with the closely related Marburg virus shows that the N-terminal region of nucleoprotein defines the inner diameter of the Ebola virus NC, whereas the RNA genome defines its length. Binding of the nucleoprotein to RNA can assemble a loosely coiled NC-like structure; the loose coil can be condensed by binding of the viral matrix protein VP40 to the C terminus of the nucleoprotein, and rigidified by binding of VP24 and VP35 to alternate copies of the nucleoprotein. Four proteins (NP, VP24, VP35, and VP40) are necessary and sufficient to mediate assembly of an NC with structure, symmetry, variability, and flexibility indistinguishable from that in Ebola virus particles released from infected cells. Together these data provide a structural and architectural description of Ebola virus and define the roles of viral proteins in its structure and assembly.

  15. Identification of a Novel Recombinant Type 2 Porcine Reproductive and Respiratory Syndrome Virus in China

    Directory of Open Access Journals (Sweden)

    Long Zhou

    2018-03-01

    Full Text Available Since the emergence of NADC30-like porcine reproductive and respiratory syndrome virus (PRRSV in China in 2013, PRRSVs have undergone rapid evolution. In this study, a novel variant of PRRSV strain (designated SCcd17 was successfully isolated from piglets with clinical signs in Sichuan Province in China in 2017, and the complete genomic sequence was determined. The genome of this new isolate was 15,015 nucleotides (nt long, and comparative analysis revealed that SCcd17 exhibited 90.2%, 85.2%, 84.9%, and 84.0% nucleotide similarity to PRRSVs NADC30, JXA1, CH-1a, and VR-2332, respectively. Phylogenetic analysis indicated that the SCcd17 strain was classified into the NADC30-like sub-genotype, in which all the strains contained the unique discontinuous 131-amino acid deletion in nonstructural protein 2 (nsp2 when compared to VR-2332-like viruses. Notably, extensive amino acid substitutions were observed in nsp2 and a unique single amino acid deletion at position 33 of the GP5 is being described for the first time. Strikingly, recombination analysis revealed that SCcd17 was the result of recombination between the NADC30-like, JXA1-like, and VR-2332-like strains at five recombination breakpoints: nsp1α (nt 641, nsp3 (nt 5141, nsp10 (nt 9521, open reading frame 3 (ORF3 (nt 12,581, and ORF4 (nt 13,021. The genomic data of SCcd17 will be helpful for understanding the role of genomic recombination in the evolution of PRRSV.

  16. The role of cytomegalovirus, Haemophilus influenzae and Epstein Barr virus in Guillain Barre syndrome.

    Directory of Open Access Journals (Sweden)

    Shahriar Nafissi

    2013-06-01

    Full Text Available Guillain Barre Syndrome (GBS is an inflammatory, usually demyelinating, polyneuropathy; clinically characterized by acute onset of symmetric progressive muscle weakness with loss of myotatic reflexes. Thirty five patients with GBS, defined clinically according to the criteria of Asbury and Cornblath, were recruited from three hospital affiliated to Tehran University of Medical Sciences.As a control group 35 age and sex matched patients with other neurological diseases admitted to the same hospital at the same time, were included in our study. Serum samples were collected before treatment from each patient (within 4 weeks after the disease onset and controls, and stored frozen at -80ºC until serologic assays were done. Serologic testing of pretreatment serum was performed in all patients. Positive titer of virus specific IgM antibody against cytomegalovirus (CMV was found in 6 cases and 2 controls. 34 patients and 31 controls had high titer of anti Haemophilus influenzae IgG and one patient had serologic evidence of a recent Epstein Barr virus (EBV infection. The mean titer of IgG antibody against Haemophilus influenzae in cases and controls was 5.21 and 2.97 respectively. Although serologic evidence of all these infections were more frequent in cases than in controls, only Haemophilus influenzae infection appeared to be significantly related to GBS (P=0.002. Eleven cases and 3 controls had high titers of IgG antibody against Haemophilus influenzae type B (titer >8. There is significant association between high titer of IgG antibody against Haemophilus influenzae and GBS (P=0.017. Our results provide further evidence that Haemophilus influenzae and probably CMV, can be associated with GBS.

  17. Structure and Dynamics of the tRNA-like Structure Domain of Brome Mosaic Virus

    Science.gov (United States)

    Vieweger, Mario; Nesbitt, David

    2014-03-01

    Conformational switching is widely accepted as regulatory mechanism in gene expression in bacterial systems. More recently, similar regulation mechanisms are emerging for viral systems. One of the most abundant and best studied systems is the tRNA-like structure domain that is found in a number of plant viruses across eight genera. In this work, the folding dynamics of the tRNA-like structure domain of Brome Mosaic Virus are investigated using single-molecule Fluorescence Resonance Energy Transfer techniques. In particular, Burst fluorescence is applied to observe metal-ion induced folding in freely diffusing RNA constructs resembling the 3'-terminal 169nt of BMV RNA3. Histograms of EFRET probabilities reveal a complex equilibrium of three distinct populations. A step-wise kinetic model for TLS folding is developed in accord with the evolution of conformational populations and structural information in the literature. In this mechanism, formation of functional TLS domains from unfolded RNAs requires two consecutive steps; 1) hybridization of a long-range stem interaction followed by 2) formation of a 3' pseudoknot. This three-state equilibrium is well described by step-wise dissociation constants K1(328(30) μM) and K2(1092(183) μM) for [Mg2+] and K1(74(6) mM) and K2(243(52) mM) for [Na+]-induced folding. The kinetic model is validated by oligo competition with the STEM interaction. Implications of this conformational folding mechanism are discussed in regards to regulation of virus replication.

  18. Three-Dimensional Architecture and Biogenesis of Membrane Structures Associated with Plant Virus Replication

    Directory of Open Access Journals (Sweden)

    Xuejiao Jin

    2018-01-01

    Full Text Available Positive-sense (+ RNA viruses represent the most abundant group of viruses and are dependent on the host cell machinery to replicate. One remarkable feature that occurs after (+ RNA virus entry into cells is the remodeling of host endomembranes, leading to the formation of viral replication factories. Recently, rapid progress in three-dimensional (3D imaging technologies, such as electron tomography (ET and focused ion beam-scanning electron microscopy (FIB-SEM, has enabled researchers to visualize the novel membrane structures induced by viruses at high resolution. These 3D imaging technologies provide new mechanistic insights into the viral infection cycle. In this review, we summarize the latest reports on the cellular remodeling that occurs during plant virus infection; in particular, we focus on studies that provide 3D architectural information on viral replication factories. We also outline the mechanisms underlying the formation of these membranous structures and discuss possible future research directions.

  19. Epstein–Barr Virus Susceptibility in Activated PI3Kδ Syndrome (APDS Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Jean-Marie Carpier

    2018-01-01

    Full Text Available Activated PI3Kδ Syndrome (APDS is an inherited immune disorder caused by heterozygous, gain-of-function mutations in the genes encoding the phosphoinositide 3-kinase delta (PI3Kδ subunits p110δ or p85δ. This recently described primary immunodeficiency disease (PID is characterized by recurrent sinopulmonary infections, lymphoproliferation, and susceptibility to herpesviruses, with Epstein–Barr virus (EBV infection being most notable. A broad range of PIDs having disparate, molecularly defined genetic etiology can cause susceptibility to EBV, lymphoproliferative disease, and lymphoma. Historically, PID patients with loss-of-function mutations causing defective cell-mediated cytotoxicity or antigen receptor signaling were found to be highly susceptible to pathological EBV infection. By contrast, the gain of function in PI3K signaling observed in APDS patients paradoxically renders these patients susceptible to EBV, though the underlying mechanisms are incompletely understood. At a cellular level, APDS patients exhibit deranged B lymphocyte development and defects in class switch recombination, which generally lead to defective immunoglobulin production. Moreover, APDS patients also demonstrate an abnormal skewing of T cells toward terminal effectors with short telomeres and senescence markers. Here, we review APDS with a particular focus on how the altered lymphocyte biology in these patients may confer EBV susceptibility.

  20. Emerging of two new subgenotypes of porcine reproductive and respiratory syndrome viruses in Southeast China.

    Science.gov (United States)

    Zhang, Qiaoya; Xu, Xiaojie; You, Shumei; Li, Yufeng; Wang, Haiyan; Bai, Juan; Jiang, Ping

    2016-08-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the leading swine pathogens and causes major economic loss to the global swine industry. In this study, a total of 49 PRRSV isolates were collected from different swine herds in seven provinces in Southeast China from 2014 to 2015. All the ORF5 genes and some Nsp2 genes were sequenced. Phylogenetic analysis showed that all the isolates belonged to the North America genotype. Among them, five isolates formed a new subgenotype IV derived from highly pathogenic PRRSV (HP-PRRSV). Six isolates formed subgenotype III, which were closely related to the NADC30 strain in the US. These isolates formed 13 putative N-linked glycosylation site (NGS) patterns based on N30, 33, 34, 35, 44 and 51. There were fewer NGSs of isolates in subgenotype IV than in subgenotype III. This indicates that the two new subgenotypes of PRRSV strains with different NGS patterns were spreading in those regions of China. The genetic diversity should be considered for the control and prevention of this disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Use of etanercept in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients.

    Science.gov (United States)

    Ting, Patricia T; Koo, John Y

    2006-06-01

    Etanercept (Enbrel, Amgen, Thousand Oaks, CA), a soluble p75 tumor necrosis factor receptor:FC (TNFR:FC) fusion protein for plasma cytokines, specifically tumor necrosis factor-alpha (TNF-alpha), is used in the treatment of immune-mediated rheumatic diseases. To our knowledge, the use of etanercept in patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) is relatively uncommon. The main purpose of this short review is to examine the safety of etanercept in patients with HIV/AIDS. A Medline search was conducted using the keywords etanercept and HIV and/or AIDS for any published articles between 1966 to the present (September 2004). A case report, one case series, and one clinical trial pertained to the use of etanercept in HIV patients. No reports were found on the use of etanercept in AIDS. In addition, two case reports were found documenting the use of infliximab in HIV patients. Preliminary reports indicate that the administration of etanercept does not appear to increase the morbidity or mortality rates in HIV. The inhibition of TNF-alpha may actually improve the symptoms of HIV/AIDS-associated aphthous ulcers, cachexia, dementia, fatigue, and fever, as well as help manage concomitant rheumatic diseases and psoriasis. The use of etanercept shows promise for applications in disease management in patients with HIV/AIDS. Continued research efforts are necessary to establish the long-term safety and efficacy of etanercept and other biologic agents in this patient population.

  2. Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.

    Science.gov (United States)

    See, Raymond H; Petric, Martin; Lawrence, David J; Mok, Catherine P Y; Rowe, Thomas; Zitzow, Lois A; Karunakaran, Karuna P; Voss, Thomas G; Brunham, Robert C; Gauldie, Jack; Finlay, B Brett; Roper, Rachel L

    2008-09-01

    Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage.

  3. White spot syndrome virus epizootic in cultured Pacific white shrimp Litopenaeus vannamei (Boone) in Taiwan.

    Science.gov (United States)

    Cheng, L; Lin, W-H; Wang, P-C; Tsai, M-A; Hsu, J-P; Chen, S-C

    2013-12-01

    White spot syndrome virus (WSSV) has caused significant losses in shrimp farms worldwide. Between 2004 and 2006, Pacific white shrimp Litopenaeus vannamei (Boone) were collected from 220 farms in Taiwan to determine the prevalence and impact of WSSV infection on the shrimp farm industry. Polymerase chain reaction (PCR) analysis detected WSSV in shrimp from 26% of farms. Juvenile shrimp farms had the highest infection levels (38%; 19/50 farms) and brooder shrimp farms had the lowest (5%; one of 20 farms). The average extent of infection at each farm was as follows for WSSV-positive farms: post-larvae farms, 71%; juvenile farms, 61%; subadult farms, 62%; adult farms, 49%; and brooder farms, 40%. Characteristic white spots, hypertrophied nuclei and basophilic viral inclusion bodies were found in the epithelia of gills and tail fans, appendages, cephalothorax and hepatopancreas, and virions of WSSV were observed. Of shrimp that had WSSV lesions, 100% had lesions on the cephalothorax, 96% in gills and tail fans, 91% on appendages and 17% in the hepatopancreas. WSSV was also detected in copepoda and crustaceans from the shrimp farms. Sequence comparison using the pms146 gene fragment of WSSV showed that isolates from the farms had 99.7-100% nucleotide sequence identity with four strains in the GenBank database--China (AF332093), Taiwan (AF440570 and U50923) and Thailand (AF369029). This is the first broad study of WSSV infection in L. vannamei in Taiwan. © 2013 John Wiley & Sons Ltd.

  4. Hematological changes in white spot syndrome virus-infected shrimp, Fenneropenaeus chinensis (Osbeck)

    Science.gov (United States)

    Feng, Shouming; Zhan, Wenbin; Xing, Jing; Li, Jun; Yang, Kai; Wang, Jing

    2008-08-01

    The pathological changes of hemocytes in the haemolymph and hepatopancreas were examined in experimentally and naturally WSSV (white spot syndrome virus) infected Fenneropenaeus chinensis. The results showed that the pathological manifestations of hemocytes were similar among moribund shrimps infected via injection, feeding and by nature. Firstly, the total hemocyte counts (THCs) in WSSV-infected shrimp were significantly lower than those in healthy shrimp. Secondly, necrotic, broken and disintegrated cells were often observed, and a typical hematolysis was present in the haemolymph smear of WSSV-infected shrimp. Thirdly, necrosis and typical apoptosis of hemocytes were detected with TEM in the peripheral haemolymph of WSSV-infected shrimp. Hyalinocytes and semi-granulocytes with masses of WSSVs in their nuclei often appeared, whereas no granular hemocytes with WSSV were found in the hepatopancreas of moribund infected shrimps. All our results supported that hemocytes were the main target cells of WSSV, and hyalinocytes and semigranular hemocytes seemed to be more favorable for WSSV infection in F. chinensis.

  5. Epigallocatechin-3-gallate protects Kuruma shrimp Marsupeneaus japonicus from white spot syndrome virus and Vibrio alginolyticus.

    Science.gov (United States)

    Wang, Zhi; Sun, Baozhen; Zhu, Fei

    2018-07-01

    Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and exhibits potential antibacterial and anticancer activities. In this study, EGCG was used in pathogen-challenge experiments in shrimp to discover its effect on the innate immune system of an invertebrate. Kuruma shrimp Marsupeneaus japonicus was used as an experimental model and challenged with white spot syndrome virus (WSSV) and the Gram-negative bacterium Vibrio alginolyticus. Pathogen-challenge experiments showed that EGCG pretreatment significantly delayed and reduced mortality upon WSSV and V. alginolyticus infection, with VP-28 copies of WSSV also reduced. Quantitative reverse transcription polymerase chain reaction revealed the positive influence of EGCG on several innate immune-related genes, including IMD, proPO, QM, myosin, Rho, Rab7, p53, TNF-alpha, MAPK, and NOS, and we observed positive influences on three immune parameters, including total hemocyte count and phenoloxidase and superoxide dismutase activities, by EGCG treatment. Additionally, results showed that EGCG treatment significantly reduced apoptosis upon V. alginolyticus challenge. These results indicated the positive role of EGCG in the shrimp innate immune system as an enhancer of immune parameters and an inhibitor of apoptosis, thereby delaying and reducing mortality upon pathogen challenge. Our findings provide insight into potential therapeutic or preventive functions associated with EGCG to enhance shrimp immunity and protect shrimp from pathogen infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Hypoxia increases susceptibility of Pacific white shrimp to whitespot syndrome virus (WSSV

    Directory of Open Access Journals (Sweden)

    M. Lehmann

    2016-04-01

    Full Text Available The present study aimed to evaluate the mortality, reactive oxygen species production (ROS and total hemocyte counts (THC of the marine shrimp Litopenaeus vannamei infected with the white spot syndrome virus (WSSV at three levels of oxygen saturation. For this, 360 shrimp (20±2g were distributed in 24 tanks (60L, divided in two groups (infected and non-infected, which were subjected to 30, 60 and 100% of dissolved oxygen saturation (in quadruplicate. During 96 hours after infection, daily hemolymph samples were collected for hemato-immunological parameter evaluation (THC and ROS and dead animals were removed and computed to assess cumulative mortality rates. In the infected group, animals subjected to 100% saturation showed higher ROS production (P<0.05 after 48 hours, while THC was significantly reduced (P<0.05, regardless of oxygen saturation. The hypoxia resulted in high mortality when compared to 100% saturation condition. In the uninfected group, no significant differences were observed in all evaluated parameters. Thus, the hypoxia condition increased the susceptibility of shrimp to the infection of WSSV, which may be partly related to the low ROS production showed by the animals subjected to 30% oxygen saturation.

  7. Comparisons of the genetic structure of populations of Turnip mosaic virus in west east Eurasia

    Czech Academy of Sciences Publication Activity Database

    Tomimura, K.; Špak, Josef; Katis, N.; Jenner, C. E.; Walsh, J.A.; Gibbs, A.J.; Ohshima, K.

    2004-01-01

    Roč. 330, - (2004), 408-423 ISSN 0042-6822 Institutional research plan: CEZ:AV0Z5051902 Keywords : mosaic virus * genetic structure Subject RIV: EE - Microbiology, Virology Impact factor: 3.071, year: 2004

  8. Altered intrahemispheric structural connectivity in Gilles de la Tourette syndrome

    Directory of Open Access Journals (Sweden)

    Bastian Cheng

    2014-01-01

    Full Text Available Gilles de la Tourette syndrome (GTS is a common developmental neuropsychiatric disorder characterized by tics and frequent psychiatric comorbidities, often causing significant disability. Tic generation has been linked to disturbed networks of brain areas involved in planning, controlling and execution of actions, particularly structural and functional disorders in the striatum and cortico–striato–thalamo–cortical loops. We therefore applied structural diffusion tensor imaging (DTI to characterize changes in intrahemispheric white matter connectivity in cortico-subcortical circuits engaged in motor control in 15 GTS patients without psychiatric comorbidities. White matter connectivity was analyzed by probabilistic fiber tractography between 12 predefined cortical and subcortical regions of interest. Connectivity values were combined with measures of clinical severity rated by the Yale Global Tic Severity Scale (YGTSS. GTS patients showed widespread structural connectivity deficits. Lower connectivity values were found specifically in tracts connecting the supplementary motor areas (SMA with basal ganglia (pre-SMA–putamen, SMA–putamen and in frontal cortico-cortical circuits. There was an overall trend towards negative correlations between structural connectivity in these tracts and YGTSS scores. Structural connectivity of frontal brain networks involved in planning, controlling and executing actions is reduced in adult GTS patients which is associated with tic severity. These findings are in line with the concept of GTS as a neurodevelopmental disorder of brain immaturity.

  9. Study of Testicular Structure in Fetuses with Prune Belly Syndrome.

    Science.gov (United States)

    Favorito, Luciano A; Costa, Suelen F; Costa, Waldemar S; Vieiralves, Rodrigo; Bernardo, Fabio O; Sampaio, Francisco J B

    2017-01-01

    To compare the structure of the testis in fetuses with prune belly syndrome (PBS) to normal controls. We studied 6 testes obtained from 3 fetuses with PBS and 14 testes from 7 male fetuses. The testicular specimens were cut into 5- μ m thick sections and stained with hematoxylin and eosin (HE), to observe the seminiferous tubules; Weigert's solution to observe elastic fibers; and picrosirius red to observe collagen. The images were captured with an Olympus BX51 microscope and Olympus DP70 camera. The stereological analysis was done with the Image Pro and Image J programs. Means were statistically compared using the Mann-Whitney U test ( p < 0.005). Quantitative analysis documented no differences ( p = 0.4) in number of seminiferous tubules (ST) in PBS testes (mean = 8.87%, SD = 1.59), when compared to the control (mean = 11.4%, SD = 2.99) and no differences ( p = 0.8) in diameter of ST in PBS testes (mean = 52.85  μ m, SD = 1.58) when compared to the control group (mean = 53.17  μ m, SD = 1.55), but we did observe a lower number ( p = 0.0002) of Leydig cells in the PBS testes (mean = 67.03% and SD = 3.697) when compared to the control group (mean = 90.1% and SD = 2.986). Our study showed a lower concentration of Leydig cells in the triad syndrome fetuses.

  10. Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)*

    Science.gov (United States)

    Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

    2016-01-01

    Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm. Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection. PMID:26953343

  11. Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV).

    Science.gov (United States)

    Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

    2016-04-22

    Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Structural and Functional Studies on the Fusion and Attachment Envelope Glycoproteins of Nipah Virus and Hendra Virus

    Science.gov (United States)

    2003-01-01

    including measles virus (MeV), mumps virus, Sendai virus (SeV), Newcastle disease virus (NDV), rinderpest virus, canine distemper virus (CDV), human...Institute of Health, Bethesda, MD. Hut 102, MT2, MT4, and CEM human T cell lines were provided by Chou-Zen Giam, USUHS, Bethesda, MD. The human osteosarcoma

  13. Structural and Functional Analyses of the Severe Acute Respiratory Syndrome Coronavirus Endoribonuclease Nsp15

    Energy Technology Data Exchange (ETDEWEB)

    Bhardwaj, Kanchan; Palaninathan, Satheesh; Alcantara, Joanna Maria Ortiz; Yi, Lillian Li; Guarino, Linda; Sacchettini, James C.; Kao, C. Cheng (TAM)

    2008-03-31

    The severe acute respiratory syndrome (SARS) coronavirus encodes several RNA-processing enzymes that are unusual for RNA viruses, including Nsp15 (nonstructural protein 15), a hexameric endoribonuclease that preferentially cleaves 3' of uridines. We solved the structure of a catalytically inactive mutant version of Nsp15, which was crystallized as a hexamer. The structure contains unreported flexibility in the active site of each subunit. Substitutions in the active site residues serine 293 and proline 343 allowed Nsp15 to cleave at cytidylate, whereas mutation of leucine 345 rendered Nsp15 able to cleave at purines as well as pyrimidines. Mutations that targeted the residues involved in subunit interactions generally resulted in the formation of catalytically inactive monomers. The RNA-binding residues were mapped by a method linking reversible cross-linking, RNA affinity purification, and peptide fingerprinting. Alanine substitution of several residues in the RNA-contacting portion of Nsp15 did not affect hexamer formation but decreased the affinity of RNA binding and reduced endonuclease activity. This suggests a model for Nsp15 hexamer interaction with RNA.

  14. Adeno-associated virus-mediated rescue of the cognitive defects in a mouse model for Angelman syndrome.

    Directory of Open Access Journals (Sweden)

    Jennifer L Daily

    Full Text Available Angelman syndrome (AS, a genetic disorder occurring in approximately one in every 15,000 births, is characterized by severe mental retardation, seizures, difficulty speaking and ataxia. The gene responsible for AS was discovered to be UBE3A and encodes for E6-AP, an ubiquitin ligase. A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. While most human disorders characterized by severe mental retardation involve abnormalities in brain structure, no gross anatomical changes are associated with AS. However, we have determined that abnormal calcium/calmodulin-dependent protein kinase II (CaMKII regulation is seen in the maternal UBE3A deletion AS mouse model and is responsible for the major phenotypes. Specifically, there is an increased αCaMKII phosphorylation at the autophosphorylation sites Thr(286 and Thr(305/306, resulting in an overall decrease in CaMKII activity. CaMKII is not produced until after birth, indicating that the deficits associated with AS are not the result of developmental abnormalities. The present studies are focused on exploring the potential to rescue the learning and memory deficits in the adult AS mouse model through the use of an adeno-associated virus (AAV vector to increase neuronal UBE3A expression. These studies show that increasing the levels of E6-AP in the brain using an exogenous vector can improve the cognitive deficits associated with AS. Specifically, the associative learning deficit was ameliorated in the treated AS mice compared to the control AS mice, indicating that therapeutic intervention may be possible in older AS patients.

  15. Polarisation of major histocompatibility complex II host genotype with pathogenesis of European Brown Hare syndrome virus.

    Directory of Open Access Journals (Sweden)

    Christos Iacovakis

    Full Text Available A study was conducted in order to determine the occurrence of European Brown Hare Syndrome virus (EBHSV in Denmark and possible relation between disease pathogenesis and Major Histocompatibility Complex (MHC host genotype. Liver samples were examined from 170 brown hares (hunted, found sick or dead, collected between 2004 and 2009. Macroscopical and histopathological findings consistent with EBHS were detected in 24 (14.1% hares; 35 (20.6% had liver lesions not typical of the syndrome, 50 (29.4% had lesions in other tissues and 61 (35.9% had no lesions. Sixty five (38.2% of 170 samples were found to be EBHSV-positive (RT-PCR, VP60 gene. In order to investigate associations between viral pathogenesis and host genotype, variation within the exon 2 DQA gene of MHC was assessed. DQA exon 2 analysis revealed the occurrence of seven different alleles in Denmark. Consistent with other populations examined so far in Europe, observed heterozygosity of DQA (H o = 0.1180 was lower than expected (H e = 0.5835. The overall variation for both nucleotide and amino acid differences (2.9% and 14.9%, respectively were lower in Denmark than those assessed in other European countries (8.3% and 16.9%, respectively. Within the peptide binding region codons the number of nonsynonymous substitutions (dN was much higher than synonymous substitutions (dS, which would be expected for MHC alleles under balancing selection. Allele frequencies did not significantly differ between EBHSV-positive and -negative hares. However, allele Leeu-DQA*30 was detected in significantly higher (P = 0.000006 frequency among the positive hares found dead with severe histopathological lesions than among those found sick or apparently healthy. In contrast, the latter group was characterized by a higher frequency of the allele Leeu-DQA*14 as well as the proportion of heterozygous individuals (P = 0.000006 and P = 0.027. These data reveal a polarisation between EBHSV

  16. Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren’s Syndrome

    Directory of Open Access Journals (Sweden)

    Yu-Ching Lee

    2013-01-01

    Full Text Available We have previously isolated several IgG rheumatoid factors (RFs from patients with both rheumatoid arthritis and idiopathic thrombocytopenia purpura using phage display system. To study IgG RFs in patients with other autoimmune diseases, phage display antibody libraries from a hepatitis C virus infected patient with Sjögren’s syndrome were constructed. After panning, a specific clone RFL11 was isolated for characterization in advance. The binding activity and specificity of RFL11 to IgG Fc fragment were comparable to those of RFs previously isolated. The analysis with existed RF-Fc complex structures indicated the homology model of RFL11 is similar to IgM RF61 complex with high binding affinity of about 6×10-8 M. This effect resulted from longer complementarity-determining region (CDR combining key somatic mutations. In the RFL11-Fc interfaces, the CDR-H3 loop forms a finger-like structure extending into the bottom of Fc pocket and resulting in strong ion and cation-pi interactions. Moreover, a process of antigen-driven maturation was proven by somatically mutated VH residues on H2 and H3 CDR loops in the interfaces. Taken together, these results suggested that high affinity IgG RFs can be generated in patients with Sjögren’s syndrome and may play an important role in the pathogenesis of this autoimmune disease.

  17. Immunogenicity and protective efficacy of Semliki forest virus replicon-based DNA vaccines encoding goatpox virus structural proteins

    International Nuclear Information System (INIS)

    Zheng Min; Jin Ningyi; Liu Qi; Huo Xiaowei; Li Yang; Hu Bo; Ma Haili; Zhu Zhanbo; Cong Yanzhao; Li Xiao; Jin Minglan; Zhu Guangze

    2009-01-01

    Goatpox, caused by goatpox virus (GTPV), is an acute feverish and contagious disease in goats often associated with high morbidity and high mortality. To resolve potential safety risks and vaccination side effects of existing live attenuated goatpox vaccine (AV41), two Semliki forest virus (SFV) replicon-based bicistronic expression DNA vaccines (pCSm-AAL and pCSm-BAA) which encode GTPV structural proteins corresponding to the Vaccinia virus proteins A27, L1, A33, and B5, respectively, were constructed. Then, theirs ability to induce humoral and cellular response in mice and goats, and protect goats against virulent virus challenge were evaluated. The results showed that, vaccination with pCSm-AAL and pCSm-BAA in combination could elicit strong humoral and cellular responses in mice and goats, provide partial protection against viral challenge in goats, and reduce disease symptoms. Additionally, priming vaccination with the above-mentioned DNA vaccines could significantly reduce the goats' side reactions from boosting vaccinations with current live vaccine (AV41), which include skin lesions at the inoculation site and fevers. Data obtained in this study could not only facilitate improvement of the current goatpox vaccination strategy, but also provide valuable guidance to suitable candidates for evaluation and development of orthopoxvirus vaccines.

  18. Porcine reproductive and respiratory syndrome virus: antigenic and molecular diversity of British isolates and implications for diagnosis.

    Science.gov (United States)

    Frossard, Jean-Pierre; Fearnley, Catherine; Naidu, Brindha; Errington, Jane; Westcott, David G; Drew, Trevor W

    2012-08-17

    Porcine reproductive and respiratory syndrome (PRRS) is an endemic disease of pigs, caused by PRRS virus, a member of the Arteriviridae family. First seen in Britain in 1991, the disease continues to be a significant economic and welfare problem for pig producers. To date, only PRRSV genotype 1 has been found in Britain. At the genetic level, a considerable increase has been reported in the diversity of PRRS viruses isolated in Britain between 2003 and 2007, versus the early 1990 s. In this study, the diversity has been shown to extend to the antigenic level too, with potential consequences for diagnostic methods. Antigenic diversity was assessed using a panel of twelve monoclonal antibodies, only one of which reacted with all isolates tested. Nine diverse viruses were compared as potential antigens in immunoperoxidase monolayer assays, where each one produced quite different results for a common panel of sera. As a single virus is used in each diagnostic assay, results must therefore be interpreted cautiously. For a real-time RT-PCR assay, published oligonucleotide primer and probe sequences were evaluated against available genetic sequences of British and European viruses, and were re-designed where considerable mismatches were found. The multiplex assay incorporating these modified primers to detect genotype 1 and 2 PRRS viruses was then validated for use with diagnostic sera and tissues. As the increasing degree of diversity exhibited by British strains is mirrored in other countries, PRRSV will continue to provide an ongoing challenge to diagnosis at a global, as well as national level. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  19. Congenital Tracheobronchomegaly (Mounier-Kuhn Syndrome) in a Woman with Human Immunodeficiency Virus: A Case Report.

    Science.gov (United States)

    Fletcher, Amanda; Stowell, Justin; Jamoulis, Socrates

    2017-04-04

    Congenital tracheobronchomegaly (Mounier-Kuhn Syndrome, MKS) is a rare idiopathic disorder characterized by dilation of the central airways, including the trachea and first through fourth order bronchi. MKS disproportionately affects men and results in chronic respiratory tract infections. The diagnosis is made through the synthesis of clinical and radiological data. Here we report a unique case of MKS in a patient with human immunodeficiency virus (HIV) infection. A 45-year-old African American woman with a past medical history of HIV, tobacco and recreational drug abuse, chronic obstructive pulmonary disease, sleep apnea, and a 15-year history of recurrent respiratory infections presented with dyspnea, wheezing, a productive cough, increased yellow-green sputum production, and subjective fevers. Computerized tomography (CT) of the chest revealed striking dilation of the trachea and central bronchi. Fiberoptic bronchoscopy demonstrated a dilated trachea and bronchial tree with complete collapse of the trachea and bilateral mainstem bronchi during expiration. Serial imaging over 14 years allowed the radiologist to confidently diagnose her underlying disorder and recommend appropriate clinical management, which included mucolytics, chest physiotherapy, prophylactic vaccinations, and antibiotics during infectious exacerbations. To the best of our knowledge, there is only one reported case of MKS in the setting of HIV in the English literature. We report the second such case and outline the clinical presentation, diagnostic criteria, and management of MKS with the hope that increased awareness will prevent delayed or misdiagnosis for patients with MKS. This case highlights the common diagnostic delay for MKS and the need to include MKS in the differential diagnosis of recurrent respiratory tract infections.

  20. Science and ethics of human immunodeficiency virus/acquired immunodeficiency syndrome controversies in Africa.

    Science.gov (United States)

    Brewster, David

    2011-09-01

    The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic in Africa has raised important ethical issues for both researchers and clinicians. The most notorious controversy has been related to the zidovudine (AZT) trials in Africa in the late 1990s, in which the control groups were given a placebo rather than an effective drug to prevent vertical transmission. This raised concerns in the sponsoring country about exploitation of subjects, injustice and an ethical double standard between donor countries and resource-poor settings. However, the real double standard is between clinical practice standards in Western versus African countries, which must be addressed as part of the increasing global inequity of wealth both between countries and also within countries. There are important limitations to ethical declarations, principles and guidelines on their own without contextual ethical reasoning. The focus on research ethics with the HIV epidemic has led to a relative neglect of ethical issues in clinical practice. Although the scientific advances in HIV/AIDS have changed the ethical issues since the 1990s, there has also been progress in the bioethics of HIV/AIDS in terms of ethical review capability by local committees as well as in exposure to ethical issues by clinicians and researchers in Africa. However, serious concerns remain about the overregulation of research by bureaucratic agencies which could discourage African research on specifically African health issues. There is also a need for African academic institutions and researchers to progressively improve their research capacity with the assistance of research funders and donor agencies. © 2011 The Author. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  1. Reactomes of porcine alveolar macrophages infected with porcine reproductive and respiratory syndrome virus.

    Directory of Open Access Journals (Sweden)

    Zhihua Jiang

    Full Text Available Porcine reproductive and respiratory syndrome (PRRS has devastated pig industries worldwide for many years. It is caused by a small RNA virus (PRRSV, which targets almost exclusively pig monocytes or macrophages. In the present study, five SAGE (serial analysis of gene expression libraries derived from 0 hour mock-infected and 6, 12, 16 and 24 hours PRRSV-infected porcine alveolar macrophages (PAMs produced a total 643,255 sequenced tags with 91,807 unique tags. Differentially expressed (DE tags were then detected using the Bayesian framework followed by gene/mRNA assignment, arbitrary selection and manual annotation, which determined 699 DE genes for reactome analysis. The DAVID, KEGG and REACTOME databases assigned 573 of the DE genes into six biological systems, 60 functional categories and 504 pathways. The six systems are: cellular processes, genetic information processing, environmental information processing, metabolism, organismal systems and human diseases as defined by KEGG with modification. Self-organizing map (SOM analysis further grouped these 699 DE genes into ten clusters, reflecting their expression trends along these five time points. Based on the number one functional category in each system, cell growth and death, transcription processes, signal transductions, energy metabolism, immune system and infectious diseases formed the major reactomes of PAMs responding to PRRSV infection. Our investigation also focused on dominant pathways that had at least 20 DE genes identified, multi-pathway genes that were involved in 10 or more pathways and exclusively-expressed genes that were included in one system. Overall, our present study reported a large set of DE genes, compiled a comprehensive coverage of pathways, and revealed system-based reactomes of PAMs infected with PRRSV. We believe that our reactome data provides new insight into molecular mechanisms involved in host genetic complexity of antiviral activities against PRRSV and

  2. Evolution of specific immunity in shrimp - a vaccination perspective against white spot syndrome virus.

    Science.gov (United States)

    Syed Musthaq, Syed Khader; Kwang, Jimmy

    2014-10-01

    Invertebrates lack true adaptive immunity and it solely depends on the primitive immunity called innate immunity. However, various innate immune molecules and mechanisms are identified in shrimp that plays potential role against invading bacterial, fungal and viral pathogens. Perceiving the shrimp innate immune mechanisms will contribute in developing effective vaccine strategies against major shrimp pathogens. Hence this review intends to explore the innate immune molecules of shrimp with suitable experimental evidences together with the evolution of "specific immune priming" of invertebrates. In addition, we have emphasized on the development of an effective vaccine strategy against major shrimp pathogen, white spot syndrome virus (WSSV). The baculovirus displayed rVP28 (Bac-VP28), a major envelope protein of WSSV was utilized to study its vaccine efficacy by oral route. A significant advantage of this baculovirus expression cassette is the use of WSSV-immediate early 1 (ie1) promoter that derived the abundant expression of rVP28 protein at the early stage of the infection in insect cell. The orally vaccinated shrimp with Bac-VP28 transduced successfully in the shrimp cells as well as provided highest survival rate. In support to our vaccine efficacy we analysed Pattern Recognition Proteins (PRPs) β-1,3 glucan lipopolysaccharides (LGBP) and STAT gene profiles in the experimental shrimp. Indeed, the vaccination of shrimp with Bac-VP28 demonstrated some degree of specificity with enhanced survival rate when compared to control vaccination with Bac-wt. Hence it is presumed that the concept of "specific immune priming" in relevant to shrimp immunity is possible but may not be common to all shrimp pathogens. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Shrimp miRNAs regulate innate immune response against white spot syndrome virus infection.

    Science.gov (United States)

    Kaewkascholkul, Napol; Somboonviwat, Kulwadee; Asakawa, Shuichi; Hirono, Ikuo; Tassanakajon, Anchalee; Somboonwiwat, Kunlaya

    2016-07-01

    MicroRNAs are short noncoding RNAs of RNA interference pathways that regulate gene expression through partial complementary base-pairing to target mRNAs. In this study, miRNAs that are expressed in white spot syndrome virus (WSSV)-infected Penaeus monodon, were identified using next generation sequencing. Forty-six miRNA homologs were identified from WSSV-infected shrimp hemocyte. Stem-loop real-time RT-PCR analysis showed that 11 out of 16 selected miRNAs were differentially expressed upon WSSV infection. Of those, pmo-miR-315 and pmo-miR-750 were highly responsive miRNAs. miRNA target prediction revealed that the miRNAs were targeted at 5'UTR, ORF, and 3'UTR of several immune-related genes such as genes encoding antimicrobial peptides, signaling transduction proteins, heat shock proteins, oxidative stress proteins, proteinases or proteinase inhibitors, proteins in blood clotting system, apoptosis-related proteins, proteins in prophenoloxidase system, pattern recognition proteins and other immune molecules. The highly conserved miRNA homolog, pmo-bantam, was characterized for its function in shrimp. The pmo-bantam was predicted to target the 3'UTR of Kunitz-type serine protease inhibitor (KuSPI). Binding of pmo-bantam to the target sequence of KuSPI gene was analyzed by luciferase reporter assay. Correlation of pmo-bantam and KuSPI expression was observed in lymphoid organ of WSSV-infected shrimp. These results implied that miRNAs might play roles as immune gene regulators in shrimp antiviral response. Copyright © 2016. Published by Elsevier Ltd.

  4. Reprint of "evolution of specific immunity in shrimp - a vaccination perspective against white spot syndrome virus".

    Science.gov (United States)

    Syed Musthaq, Syed Khader; Kwang, Jimmy

    2015-02-01

    Invertebrates lack true adaptive immunity and it solely depends on the primitive immunity called innate immunity. However, various innate immune molecules and mechanisms are identified in shrimp that plays potential role against invading bacterial, fungal and viral pathogens. Perceiving the shrimp innate immune mechanisms will contribute in developing effective vaccine strategies against major shrimp pathogens. Hence this review intends to explore the innate immune molecules of shrimp with suitable experimental evidences together with the evolution of "specific immune priming" of invertebrates. In addition, we have emphasized on the development of an effective vaccine strategy against major shrimp pathogen, white spot syndrome virus (WSSV). The baculovirus displayed rVP28 (Bac-VP28), a major envelope protein of WSSV was utilized to study its vaccine efficacy by oral route. A significant advantage of this baculovirus expression cassette is the use of WSSV-immediate early 1 (ie1) promoter that derived the abundant expression of rVP28 protein at the early stage of the infection in insect cell. The orally vaccinated shrimp with Bac-VP28 transduced successfully in the shrimp cells as well as provided highest survival rate. In support to our vaccine efficacy we analysed Pattern Recognition Proteins (PRPs) β-1,3 glucan lipopolysaccharides (LGBP) and STAT gene profiles in the experimental shrimp. Indeed, the vaccination of shrimp with Bac-VP28 demonstrated some degree of specificity with enhanced survival rate when compared to control vaccination with Bac-wt. Hence it is presumed that the concept of "specific immune priming" in relevant to shrimp immunity is possible but may not be common to all shrimp pathogens. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Human immunodeficiency virus (HIV) is highly associated with giant idiopathic esophageal ulcers in acquired immunodeficiency syndrome (AIDS) patients.

    Science.gov (United States)

    Lv, Bei; Cheng, Xin; Gao, Jackson; Zhao, Hong; Chen, Liping; Wang, Liwei; Huang, Shaoping; Fan, Zhenyu; Zhang, Renfang; Shen, Yinzhong; Li, Lei; Liu, Baochi; Qi, Tangkai; Wang, Jing; Cheng, Jilin

    2016-01-01

    This study aimed to determine whether the human immunodeficiency virus (HIV) exists in giant idiopathic esophageal ulcers in the patients with acquired immune deficiency syndrome (AIDS). 16 AIDS patients with a primary complaint of epigastric discomfort were examined by gastroscopy. Multiple and giant esophageal ulcers were biopsied and analyzed with pathology staining and reverse transcription-polymerase chain reaction (RT-PCR) to determine the potential pathogenic microorganisms, including HIV, cytomegalovirus (CMV) and herpes simplex viruses (HSV). HIV was detected in ulcer samples from 12 out of these 16 patients. Ulcers in 2 patients were infected with CMV and ulcers in another 2 patients were found HSV positive. No obvious cancerous pathological changes were found in these multiple giant esophageal ulcer specimens. HIV may be one of the major causative agents of multiple benign giant esophageal ulcers in AIDS patients.

  6. ISOLATION OF EGG DROP SYNDROME VIRUS AND ITS MOLECULAR CHARACTERIZATION USING SODIUM DODECYL SULPHATE POLYACRYLAMIDE GEL ELECTROPHORESIS

    Directory of Open Access Journals (Sweden)

    M. H. Rasool, S. U. Rahman and M. K. Mansoor

    2005-10-01

    Full Text Available Six isolates of egg drop syndrome (EDS virus were recovered from five different outbreaks of EDS in commercial laying hens in and around Faisalabad. The aberrant eggs were fed to the susceptible laying hens for experimental induction of infection. The samples from infected birds (egg washing, cloacal swabs, oviducts and spleens were collected, processed and inoculated into 11-day old duck embryos. The presence of virus in harvested allanto-amniotic fluid was monitored by spot and microhaemagglutination tests and confirmed by haemagglutination inhibition and agar gel precipitation tests. The EDS virus grew well in duck embryos and agglutinated only avian but not mammalian red blood cells. These isolates were purified through velocity density gradient centrifugation. Protein concentration was determined through Lowry method and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE was conducted by loading 300 µg protein concentration on 12.5% gel using discontinuous buffer system. All the six isolates showed 13 polypeptides, which were identical to those described in the referral EDS-76 virus (strain-127. The molecular weights of the polypeptides ranged from 6.5 KDa to 126 KDa.

  7. Structural study of Mason-Pfizer monkey virus protease

    Czech Academy of Sciences Publication Activity Database

    Veverka, V.; Bauerová, Helena; Hrabal, R.; Pichová, Iva

    2002-01-01

    Roč. 269, - (2002), s. 57-58 ISSN 0014-2956. [Meeting of the Federation of European Biochemical Societies /28./. 20.10.2002-25.10.2002, Istanbul] R&D Projects: GA ČR GA203/00/1241 Institutional research plan: CEZ:AV0Z4055905 Keywords : Mason-Pfizer monkey virus Subject RIV: CE - Biochemistry

  8. Zika virus: what do we know about the viral structure, mechanisms of transmission, and neurological outcomes?

    Directory of Open Access Journals (Sweden)

    Lucia Regina Cangussu da Silva

    2016-06-01

    Full Text Available Abstract: The Zika virus epidemic that started in Brazil in 2014 has spread to >30 countries and territories in Latin America, leading to a rapid rise in the incidence of microcephalic newborns and adults with neurological complications. At the beginning of the outbreak, little was known about Zika virus morphology, genome structure, modes of transmission, and its potential to cause neurological malformations and disorders. With the advancement of basic science, discoveries of the mechanisms of strain variability, viral transfer to the fetus, and neurovirulence were published. These will certainly lead to the development of strategies to block vertical viral transmission, neuronal invasion, and pathogenesis in the near future. This paper reviews the current literature on Zika virus infections, with the aim of gaining a holistic insight into their etiology and pathogenesis. We discuss Zika virus history and epidemiology in Brazil, viral structure and taxonomy, old and newly identified transmission modes, and neurological consequences of infection.

  9. Detection of a pneumonia virus of mice (PVM) in an African hedgehog (Atelerix arbiventris) with suspected wobbly hedgehog syndrome (WHS).

    Science.gov (United States)

    Madarame, Hiroo; Ogihara, Kikumi; Kimura, Moe; Nagai, Makoto; Omatsu, Tsutomu; Ochiai, Hideharu; Mizutani, Tetsyuya

    2014-09-17

    A pneumonia virus of mice (PVM) from an African hedgehog (Atelerix arbiventris) with suspected wobbly hedgehog syndrome (WHS) was detected and genetically characterized. The affected hedgehog had a nonsuppurative encephalitis with vacuolization of the white matter, and the brain samples yielded RNA reads highly homogeneous to PVM strain 15 (96.5% of full genomic sequence homology by analysis of next generation sequencing). PVM antigen was also detected in the brain and the lungs immunohistochemically. A PVM was strongly suggested as a causative agent of encephalitis of a hedgehog with suspected WHS. This is a first report of PVM infection in hedgehogs. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. High frequency RNA recombination in porcine reproductive and respiratory syndrome virus occurs preferentially between parental sequences with high similarity

    DEFF Research Database (Denmark)

    van Vugt, Joke .J.F.A.; Storgaard, Torben; Oleksiewicz, Martin B.

    2001-01-01

    Two types of porcine reproductive and respiratory syndrome virus (PRRSV) exist, a North American type and a European type. The co-existence of both types in some countries, such as Denmark, Slovakia and Canada, creates a risk of inter-type recombination. To evaluate this risk, cell cultures were co......, but no recombination was detected between the European and North American types. Calculation of the maximum theoretical risk of European-American recombination, based on the sensitivity of the RT-PCR system, revealed that RNA recombination between the European and North American types of PRRSV is at least 10000 times...

  11. Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts

    Energy Technology Data Exchange (ETDEWEB)

    Du, Yijun [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan (China); Pattnaik, Asit K. [School of Veterinary Medicine and Biomedical Sciences and the Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583-0900 (United States); Song, Cheng [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Yoo, Dongwan, E-mail: dyoo@illinois.edu [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Li, Gang, E-mail: dyoo@illinois.edu [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Institute of Animal Science and Veterinary Medicine, Chinese Academy of Agricultural Sciences, Beijing (China)

    2012-03-01

    The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 ({omega} - 2, where {omega} is the GPI moiety at E160), P159 ({omega} - 1), and M162 ({omega} + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide-anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.

  12. Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts

    International Nuclear Information System (INIS)

    Du, Yijun; Pattnaik, Asit K.; Song, Cheng; Yoo, Dongwan; Li, Gang

    2012-01-01

    The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 (ω − 2, where ω is the GPI moiety at E160), P159 (ω − 1), and M162 (ω + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide–anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.

  13. Study of Testicular Structure in Fetuses with Prune Belly Syndrome

    Directory of Open Access Journals (Sweden)

    Luciano A. Favorito

    2017-01-01

    Full Text Available Purpose. To compare the structure of the testis in fetuses with prune belly syndrome (PBS to normal controls. Materials and Methods. We studied 6 testes obtained from 3 fetuses with PBS and 14 testes from 7 male fetuses. The testicular specimens were cut into 5-μm thick sections and stained with hematoxylin and eosin (HE, to observe the seminiferous tubules; Weigert’s solution to observe elastic fibers; and picrosirius red to observe collagen. The images were captured with an Olympus BX51 microscope and Olympus DP70 camera. The stereological analysis was done with the Image Pro and Image J programs. Means were statistically compared using the Mann–Whitney U test (p<0.005. Results. Quantitative analysis documented no differences (p=0.4 in number of seminiferous tubules (ST in PBS testes (mean = 8.87%, SD=1.59, when compared to the control (mean = 11.4%, SD=2.99 and no differences (p=0.8 in diameter of ST in PBS testes (mean = 52.85 μm, SD=1.58 when compared to the control group (mean = 53.17 μm, SD=1.55, but we did observe a lower number (p=0.0002 of Leydig cells in the PBS testes (mean = 67.03% and SD=3.697 when compared to the control group (mean = 90.1% and SD=2.986. Conclusions. Our study showed a lower concentration of Leydig cells in the triad syndrome fetuses.

  14. Structural basis for the development of avian virus capsids that display influenza virus proteins and induce protective immunity.

    Science.gov (United States)

    Pascual, Elena; Mata, Carlos P; Gómez-Blanco, Josué; Moreno, Noelia; Bárcena, Juan; Blanco, Esther; Rodríguez-Frandsen, Ariel; Nieto, Amelia; Carrascosa, José L; Castón, José R

    2015-03-01

    Bioengineering of viruses and virus-like particles (VLPs) is a well-established approach in the development of new and improved vaccines against viral and bacterial pathogens. We report here that the capsid of a major avian pathogen, infectious bursal disease virus (IBDV), can accommodate heterologous proteins to induce protective immunity. The structural units of the ~70-nm-diameter T=13 IBDV capsid are trimers of VP2, which is made as a precursor (pVP2). The pVP2 C-terminal domain has an amphipathic α helix that controls VP2 polymorphism. In the absence of the VP3 scaffolding protein, 466-residue pVP2 intermediates bearing this α helix assemble into genuine VLPs only when expressed with an N-terminal His6 tag (the HT-VP2-466 protein). HT-VP2-466 capsids are optimal for protein insertion, as they are large enough (cargo space, ~78,000 nm(3)) and are assembled from a single protein. We explored HT-VP2-466-based chimeric capsids initially using enhanced green fluorescent protein (EGFP). The VLP assembly yield was efficient when we coexpressed EGFP-HT-VP2-466 and HT-VP2-466 from two recombinant baculoviruses. The native EGFP structure (~240 copies/virion) was successfully inserted in a functional form, as VLPs were fluorescent, and three-dimensional cryo-electron microscopy showed that the EGFP molecules incorporated at the inner capsid surface. Immunization of mice with purified EGFP-VLPs elicited anti-EGFP antibodies. We also inserted hemagglutinin (HA) and matrix (M2) protein epitopes derived from the mouse-adapted A/PR/8/34 influenza virus and engineered several HA- and M2-derived chimeric capsids. Mice immunized with VLPs containing the HA stalk, an M2 fragment, or both antigens developed full protection against viral challenge. Virus-like particles (VLPs) are multimeric protein cages that mimic the infectious virus capsid and are potential candidates as nonliving vaccines that induce long-lasting protection. Chimeric VLPs can display or include foreign

  15. Crystal structure of Middle East respiratory syndrome coronavirus helicase.

    Directory of Open Access Journals (Sweden)

    Wei Hao

    2017-06-01

    Full Text Available Middle East respiratory syndrome coronavirus (MERS-CoV remains a threat to public health worldwide; however, effective vaccine or drug against CoVs remains unavailable. CoV helicase is one of the three evolutionary most conserved proteins in nidoviruses, thus making it an important target for drug development. We report here the first structure of full-length coronavirus helicase, MERS-CoV nsp13. MERS-CoV helicase has multiple domains, including an N-terminal Cys/His rich domain (CH with three zinc atoms, a beta-barrel domain and a C-terminal SF1 helicase core with two RecA-like subdomains. Our structural analyses show that while the domain organization of nsp13 is conserved throughout nidoviruses, the individual domains of nsp13 are closely related to the equivalent eukaryotic domains of Upf1 helicases. The most distinctive feature differentiating CoV helicases from eukaryotic Upf1 helicases is the interaction between CH domain and helicase core.

  16. Structure of a Venezuelan equine encephalitis virus assembly intermediate isolated from infected cells

    International Nuclear Information System (INIS)

    Lamb, Kristen; Lokesh, G.L.; Sherman, Michael; Watowich, Stanley

    2010-01-01

    Venezuelan equine encephalitis virus (VEEV) is a prototypical enveloped ssRNA virus of the family Togaviridae. To better understand alphavirus assembly, we analyzed newly formed nucleocapsid particles (termed pre-viral nucleocapsids) isolated from infected cells. These particles were intermediates along the virus assembly pathway, and ultimately bind membrane-associated viral glycoproteins to bud as mature infectious virus. Purified pre-viral nucleocapsids were spherical with a unimodal diameter distribution. The structure of one class of pre-viral nucleocapsids was determined with single particle reconstruction of cryo-electron microscopy images. These studies showed that pre-viral nucleocapsids assembled into an icosahedral structure with a capsid stoichiometry similar to the mature nucleocapsid. However, the individual capsomers were organized significantly differently within the pre-viral and mature nucleocapsids. The pre-viral nucleocapsid structure implies that nucleocapsids are highly plastic and undergo glycoprotein and/or lipid-driven rearrangements during virus self-assembly. This mechanism of self-assembly may be general for other enveloped viruses.

  17. Ramsay Hunt syndrome

    Science.gov (United States)

    Hunt syndrome; Herpes zoster oticus; Geniculate ganglion zoster; Geniculate herpes; Herpetic geniculate ganglionitis ... The varicella-zoster virus that causes Ramsay Hunt syndrome is the same virus that causes chickenpox and ...

  18. Genome-wide analysis of Epstein-Barr virus identifies variants and genes associated with gastric carcinoma and population structure.

    Science.gov (United States)

    Yao, Youyuan; Xu, Miao; Liang, Liming; Zhang, Haojiong; Xu, Ruihua; Feng, Qisheng; Feng, Lin; Luo, Bing; Zeng, Yi-Xin

    2017-10-01

    Epstein-Barr virus is a ubiquitous virus and is associated with several human malignances, including the significant subset of gastric carcinoma, Epstein-Barr virus-associated gastric carcinoma. Some Epstein-Barr virus-associated diseases are uniquely prevalent in populations with different geographic origins. However, the features of the disease and geographically associated Epstein-Barr virus genetic variation as well as the roles that the variation plays in carcinogenesis and evolution remain unclear. Therefore, in this study, we sequenced 95 geographically distinct Epstein-Barr virus isolates from Epstein-Barr virus-associated gastric carcinoma biopsies and saliva of healthy donors to detect variants and genes associated with gastric carcinoma and population structure from a genome-wide spectrum. We demonstrated that Epstein-Barr virus revealed the population structure between North China and South China. In addition, we observed population stratification between Epstein-Barr virus strains from gastric carcinoma and healthy controls, indicating that certain Epstein-Barr virus subtypes are associated with different gastric carcinoma risks. We identified that the BRLF1, BBRF3, and BBLF2/BBLF3 genes had significant associations with gastric carcinoma. LMP1 and BNLF2a genes were strongly geographically associated genes in Epstein-Barr virus. Our study provides insights into the genetic basis of oncogenic Epstein-Barr virus for gastric carcinoma, and the genetic variants associated with gastric carcinoma can serve as biomarkers for oncogenic Epstein-Barr virus.

  19. Alteration of a second putative fusion peptide of structural glycoprotein E2 of Classical Swine Fever Virus alters virus replication and virulence in swine

    Science.gov (United States)

    E2, the major envelope glycoprotein of Classical Swine Fever Virus (CSFV), is involved in several critical virus functions including cell attachment, host range susceptibility, and virulence in natural hosts. Functional structural analysis of E2 based on Wimley-White interfacial hydrophobicity dis...

  20. Measles Virus Fusion Protein: Structure, Function and Inhibition

    Directory of Open Access Journals (Sweden)

    Philippe Plattet

    2016-04-01

    Full Text Available Measles virus (MeV, a highly contagious member of the Paramyxoviridae family, causes measles in humans. The Paramyxoviridae family of negative single-stranded enveloped viruses includes several important human and animal pathogens, with MeV causing approximately 120,000 deaths annually. MeV and canine distemper virus (CDV-mediated diseases can be prevented by vaccination. However, sub-optimal vaccine delivery continues to foster MeV outbreaks. Post-exposure prophylaxis with antivirals has been proposed as a novel strategy to complement vaccination programs by filling herd immunity gaps. Recent research has shown that membrane fusion induced by the morbillivirus glycoproteins is the first critical step for viral entry and infection, and determines cell pathology and disease outcome. Our molecular understanding of morbillivirus-associated membrane fusion has greatly progressed towards the feasibility to control this process by treating the fusion glycoprotein with inhibitory molecules. Current approaches to develop anti-membrane fusion drugs and our knowledge on drug resistance mechanisms strongly suggest that combined therapies will be a prerequisite. Thus, discovery of additional anti-fusion and/or anti-attachment protein small-molecule compounds may eventually translate into realistic therapeutic options.

  1. Relevance of capsid structure in the buckling and maturation of spherical viruses

    International Nuclear Information System (INIS)

    Aznar, María; Luque, Antoni; Reguera, David

    2012-01-01

    The shape and mechanical properties of viral capsids play an important role in several biological processes during the virus life cycle. In particular, to become infective, many viruses require a maturation stage where the capsid undergoes a buckling transition, from an initial spherical procapsid into a final icosahedral faceted shell. Here we study, using a minimal physical model, how the capsid shape and the buckling transition depend on the triangulation number T and the icosahedral class P of the virus structure. We find that, for small shells, capsids with P = 1 are most likely to produce polyhedral shapes that minimize their energy and accumulated stress, whereas viruses with P = 3 prefer to remain spherical. For big capsids, all shells are more stable adopting an icosahedral shape, in agreement with continuum elastic theory. Moreover, spherical viruses show a buckling transition to polyhedral shells under expansion, in consonance with virus maturation. The resulting icosahedral shell is mechanically stiffer, tolerates larger expansions and withstands higher internal pressures before failing, which could explain why some dsDNA viruses, which rely on the pressurization of their genetic material to facilitate the infection, undergo a buckling transition. We emphasize that the results are general and could also be applied to non-biological systems. (paper)

  2. Newcastle disease virus-attenuated vaccine co-contaminated with fowl adenovirus and chicken infectious anemia virus results in inclusion body hepatitis-hydropericardium syndrome in poultry.

    Science.gov (United States)

    Su, Qi; Li, Yang; Meng, Fanfeng; Cui, Zhizhong; Chang, Shuang; Zhao, Peng

    2018-05-01

    Inclusion body hepatitis-hydropericardium syndrome (IBH-HPS) induced by fowl adenovirus type 4 (FAdV-4) has caused huge economic losses to the poultry industry of China, but the source of infection for different flocks, especially flocks with high biological safety conditions, has remained unclear. This study tested the pathogenicity of Newcastle disease virus (NDV)-attenuated vaccine from a large-scale poultry farm in China where IBH-HPS had appeared with high mortality. Analysis revealed that the NDV-attenuated vaccine in use from the abovementioned poultry farm was simultaneously contaminated with FAdV-4 and chicken infectious anemia virus (CIAV). The FAdV and CIAV isolated from the vaccine were purified for the artificial preparation of an NDV-attenuated vaccine singly contaminated with FAdV or CIAV, or simultaneously contaminated with both of them. Seven-day-old specific pathogen-free chicks were inoculated with the artificially prepared contaminated vaccines and tested for corresponding indices. The experiments showed that no hydropericardium syndrome (HPS) and corresponding death occurred after administering the NDV-attenuated vaccine singly contaminated with FAdV or CIAV, but a mortality of 75% with IBH-HPS was commonly found in birds after administering the NDV-attenuated vaccine co-contaminated with FAdV and CIAV. In conclusion, this study found the co-contamination of FAdV-4 and CIAV in the same attenuated vaccine and confirmed that such a contaminated attenuated vaccine was a significant source of infection for outbreaks of IBH-HPS in some flocks. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain–Barré Syndrome: Systematic Review

    Science.gov (United States)

    Reveiz, Ludovic; Oladapo, Olufemi T.; Martínez-Vega, Ruth; Haefliger, Anina

    2017-01-01

    Background The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain–Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. Methods and Findings The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose–response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose–response relationship and specificity), we found that more than half the

  4. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review.

    Science.gov (United States)

    Krauer, Fabienne; Riesen, Maurane; Reveiz, Ludovic; Oladapo, Olufemi T; Martínez-Vega, Ruth; Porgo, Teegwendé V; Haefliger, Anina; Broutet, Nathalie J; Low, Nicola

    2017-01-01

    The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain-Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose-response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose-response relationship and specificity), we found that more than half the relevant studies supported a causal

  5. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review.

    Directory of Open Access Journals (Sweden)

    Fabienne Krauer

    2017-01-01

    Full Text Available The World Health Organization (WHO stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain-Barré syndrome (GBS and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality.The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose-response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693. We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose-response relationship and specificity, we found that more than half the relevant studies supported

  6. Follow-up after acute respiratory distress syndrome caused by influenza a (H1N1 virus infection

    Directory of Open Access Journals (Sweden)

    Carlos Toufen Jr.

    2011-01-01

    Full Text Available BACKGROUND: There are no reports on the long-term follow-up of patients with swine-origin influenza A virus infection that progressed to acute respiratory distress syndrome. METHODS: Four patients were prospectively followed up with pulmonary function tests and high-resolution computed tomography for six months after admission to an intensive care unit. RESULTS: Pulmonary function test results assessed two months after admission to the intensive care unit showed reduced forced vital capacity in all patients and low diffusion capacity for carbon monoxide in two patients. At six months, pulmonary function test results were available for three patients. Two patients continued to have a restrictive pattern, and none of the patients presented with abnormal diffusion capacity for carbon monoxide. All of them had a diffuse ground-glass pattern on high-resolution computed tomography that improved after six months. CONCLUSIONS: Despite the marked severity of lung disease at admission, patients with acute respiratory distress syndrome caused by swine-origin influenza A virus infection presented a late but substantial recovery over six months of follow-up.

  7. Efficacy of peroxisome proliferator activated receptor agonist in the treatment of virus-associated haemophagocytic syndrome in a rabbit model.

    Science.gov (United States)

    Hsieh, Wen-Chuan; Lan, Bau-Shin; Chen, Yi-Ling; Chang, Yao; Chuang, Huai-Chia; Su, Ih-Jen

    2010-01-01

    Virus-associated haemophagocytic syndrome (VAHS) is a fatal complication of viral infections, such as Epstein-Barr virus and H5N1 influenza, that results from macrophage activation and pro inflammatory cytokine injuries. The high comorbidity and mortality of current therapy urgently demands an ideal agent based on VAHS pathogenesis. Peroxisome proliferator activated receptor (PPAR) agonists, regulators of metabolic syndrome, can exhibit immunomodulatory effects on macrophage activation and cytokine secretion. In this study, we adopted rosiglitazone, a PPAR-gamma agonist, for VAHS control in a Herpesvirus papio (HVP)-infected rabbit model. Various doses of rosiglitazone were orally administered to rabbits on day 7 or day 20 after intravenous challenge with 5 x 10(7) copies of HVP. The rabbits that received 4 mg/day rosiglitazone had significantly increased survival when treated at an early stage of infection (P<0.01), whereas a higher dose (8 mg/day) was required at the advanced stage of the disease (P<0.05). All rosiglitazone-treated rabbits had significantly improved laboratory parameters and plasma tumour necrosis factor-alpha levels. Importantly, rosiglitazone could also inhibit viral replication in vitro and in vivo. PPAR agonists could represent a potentially new agent for the therapy of VAHS.

  8. Prevalence of Guillain-Barré syndrome among Zika virus infected cases: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Ludovica Barbi

    2018-03-01

    Full Text Available Zika virus (ZIKV is an emergent flavivirus transmitted mainly through Aedes spp. mosquitoes that is posing challenge to healthcare services in countries experiencing an outbreak. Usually ZIKV infection is mild, but in some cases it has been reported to progress into neurological diseases such as microcephaly in infants and Guillain-Barré syndrome (GBS in adults. GBS is a debilitating autoimmune disorder that affects peripheral nerves. Since ZIKV caused massive outbreaks in South America in the past few years, we aimed to systematically review the literature and perform a meta-analysis to estimate the prevalence of GBS among ZIKV-infected individuals. We searched PubMed and Cochrane databases and selected three studies for a meta-analysis. We estimated the prevalence of ZIKV-associated GBS to be 1.23% (95% CI = 1.17–1.29%. Limitations include paucity of data regarding previous flavivirus infections and ZIKV-infection confirmation issues. Our estimate seems to be low, but cannot be ignored, since ZIKV outbreaks affects an overwhelming number of individuals and GBS is a life-threatening debilitating condition, especially in pregnant women. ZIKV infection cases must be closely followed to assure prompt care to reduce the impact of GBS associated-sequelae on the quality of life of those affected. Keywords: Arboviruses, Zika virus, Guillain-Barré syndrome, Epidemiology, Emergent diseases

  9. ABHD5/CGI-58, the Chanarin-Dorfman Syndrome Protein, Mobilises Lipid Stores for Hepatitis C Virus Production.

    Directory of Open Access Journals (Sweden)

    Gabrielle Vieyres

    2016-04-01

    Full Text Available Hepatitis C virus (HCV particles closely mimic human very-low-density lipoproteins (VLDL to evade humoral immunity and to facilitate cell entry. However, the principles that govern HCV association with VLDL components are poorly defined. Using an siRNA screen, we identified ABHD5 (α/β hydrolase domain containing protein 5, also known as CGI-58 as a new host factor promoting both virus assembly and release. ABHD5 associated with lipid droplets and triggered their hydrolysis. Importantly, ABHD5 Chanarin-Dorfman syndrome mutants responsible for a rare lipid storage disorder in humans were mislocalised, and unable to consume lipid droplets or support HCV production. Additional ABHD5 mutagenesis revealed a novel tribasic motif that does not influence subcellular localization but determines both ABHD5 lipolytic and proviral properties. These results indicate that HCV taps into the lipid droplet triglyceride reservoir usurping ABHD5 lipase cofactor function. They also suggest that the resulting lipid flux, normally devoted to VLDL synthesis, also participates in the assembly and release of the HCV lipo-viro-particle. Altogether, our study provides the first association between the Chanarin-Dorfman syndrome protein and an infectious disease and sheds light on the hepatic manifestations of this rare genetic disorder as well as on HCV morphogenesis.

  10. Structural Connectivity in Gilles de la Tourette Syndrome

    Directory of Open Access Journals (Sweden)

    Ana B Chelse

    2015-04-01

    Full Text Available Investigators from Centre de Reference National Maladie Rare ‘Syndrome Gilles de la Tourette’ and Sorbonne University report white matter abnormalities in the pathways connecting the cerebral cortex, basal ganglia, and thalamus in a group of 49 adults with Tourette syndrome (TS.

  11. Discovering Structure in Auditory Input: Evidence from Williams Syndrome

    Science.gov (United States)

    Elsabbagh, Mayada; Cohen, Henri; Karmiloff-Smith, Annette

    2010-01-01

    We examined auditory perception in Williams syndrome by investigating strategies used in organizing sound patterns into coherent units. In Experiment 1, we investigated the streaming of sound sequences into perceptual units, on the basis of pitch cues, in a group of children and adults with Williams syndrome compared to typical controls. We showed…

  12. Developmental Trajectories of Structural and Pragmatic Language Skills in School-Aged Children with Williams Syndrome

    Science.gov (United States)

    Van Den Heuvel, E.; Manders, E.; Swillen, A.; Zink, I.

    2016-01-01

    Background: This study aimed to compare developmental courses of structural and pragmatic language skills in school-aged children with Williams syndrome (WS) and children with idiopathic intellectual disability (IID). Comparison of these language trajectories could highlight syndrome-specific developmental features. Method: Twelve monolingual…

  13. Twinned crystals of adeno-associated virus serotype 3b prove suitable for structural studies

    International Nuclear Information System (INIS)

    Lerch, Thomas F.; Xie, Qing; Ongley, Heather M.; Hare, Joan; Chapman, Michael S.

    2009-01-01

    Crystals of adeno-associated virus serotype 3b, a human DNA virus with promise as a vector for gene therapy, have been grown, diffract X-rays to ∼2.6 Å resolution and are suitable for structure determination in spite of twinning. Adeno-associated viruses (AAVs) are leading candidate vectors for gene-therapy applications. The AAV-3b capsid is closely related to the well characterized AAV-2 capsid (87% identity), but sequence and presumably structural differences lead to distinct cell-entry and immune-recognition properties. In an effort to understand these differences and to perhaps harness them, diffraction-quality crystals of purified infectious AAV-3b particles have been grown and several partial diffraction data sets have been recorded. The crystals displayed varying levels of merohedral twinning that in earlier times would have rendered them unsuitable for structure determination, but here is shown to be a tractable complication

  14. Lateral flow assay for rapid detection of white spot syndrome virus (WSSV) using a phage-displayed peptide as bio-recognition probe.

    Science.gov (United States)

    Kulabhusan, Prabir Kumar; Rajwade, Jyutika M; Sahul Hameed, A S; Paknikar, Kishore M

    2017-06-01

    White spot disease caused by the white spot syndrome virus (WSSV) has a major socio-economic impact on shrimp farming in India. It has been realized that a field-usable diagnostic capable of rapid detection of WSSV can prevent huge economic losses in disease outbreaks. In this work, we explored the possibility of using a peptide as bio-recognition probe in a field-usable device for the detection of WSSV from infected shrimps and prawns. A commercially available random phage-display library was screened against rVP28 (a major structural protein of WSSV, expressed as a recombinant protein in Escherichia coli). A bacteriophage clone VP28-4L was obtained, and its binding to purified rVP28 protein as well as WSSV from infected shrimp Litopaeneus vannamei tissue was confirmed by ELISA and western blot. The apparent equilibrium dissociation constant (K d ,app) was calculated to be 810 nM. VP28-4L did not show cross-reactivity with any other shrimp viruses. A 12-mer peptide (pep28, with the sequence 'TFQAFDLSPFPS') displayed on the VP28-4L was synthesized, and its diagnostic potential was evaluated in a lateral flow assay (LFA). Visual detection of WSSV could be achieved using biotinylated-pep28 and streptavidin-conjugated gold nanoparticles. In LFA, 12.5 μg/mL of the virus could be detected from L. vannamei gill tissue homogenate within 20 min. Pep28 thus becomes an attractive candidate in bio-recognition of WSSV in field-usable diagnostic platforms benefitting the aquaculture sector.

  15. Oculomotor neurocircuitry, a structural connectivity study of infantile nystagmus syndrome.

    Directory of Open Access Journals (Sweden)

    Nasser H Kashou

    Full Text Available Infantile nystagmus syndrome (INS is one of the leading causes of significant vision loss in children and affects about 1 in 1000 to 6000 births. In the present study, we are the first to investigate the structural pathways of patients and controls using diffusion tensor imaging (DTI. Specifically, three female INS patients from the same family were scanned, two sisters and a mother. Six regions of interest (ROIs were created manually to analyze the number of tracks. Additionally, three ROI masks were analyzed using TBSS (Tract-Based Spatial Statistics. The number of fiber tracks was reduced in INS subjects, compared to normal subjects, by 15.9%, 13.9%, 9.2%, 18.6%, 5.3%, and 2.5% for the pons, cerebellum (right and left, brainstem, cerebrum, and thalamus. Furthermore, TBSS results indicated that the fractional anisotropy (FA values for the patients were lower in the superior ventral aspects of the pons of the brainstem than in those of the controls. We have identified some brain regions that may be actively involved in INS. These novel findings would be beneficial to the neuroimaging clinical and research community as they will give them new direction in further pursuing neurological studies related to oculomotor function and provide a rational approach to studying INS.

  16. Packaging and structural phenotype of brome mosaic virus capsid protein with altered N-terminal β-hexamer structure

    International Nuclear Information System (INIS)

    Wispelaere, Melissanne de; Chaturvedi, Sonali; Wilkens, Stephan; Rao, A.L.N.

    2011-01-01

    The first 45 amino acid region of brome mosaic virus (BMV) capsid protein (CP) contains RNA binding and structural domains that are implicated in the assembly of infectious virions. One such important structural domain encompassing amino acids 28 QPVIV 32 , highly conserved between BMV and cowpea chlorotic mottle virus (CCMV), exhibits a β-hexamer structure. In this study we report that alteration of the β-hexamer structure by mutating 28 QPVIV 32 to 28 AAAAA 32 had no effect either on symptom phenotype, local and systemic movement in Chenopodium quinoa and RNA profile of in vivo assembled virions. However, sensitivity to RNase and assembly phenotypes distinguished virions assembled with CP subunits having β-hexamer from those of wild type. A comparison of 3-D models obtained by cryo electron microscopy revealed overall similar structural features for wild type and mutant virions, with small but significant differences near the 3-fold axes of symmetry.

  17. Biometric and structural ocular manifestations of Marfan syndrome

    Science.gov (United States)

    Gehle, Petra; Goergen, Barbara; Pilger, Daniel; Ruokonen, Peter; Robinson, Peter N.

    2017-01-01

    Background To study biometric and structural ocular manifestations of Marfan syndrome (MFS). Methods Observational, retrospective, comparative cohort study in a tertiary referral center on 285 MFS patients and 267 controls. Structural and biometric ocular characteristic were compared. Results MFS eyes were longer (axial length 24.25 ± 1.74 mm versus 23.89 ± 1.31 mm, p < 0.001) and had a flatter cornea than control eyes (mean keratometry 41.78 ± 1.80 diopters (D) versus 43.05 ± 1.51 D, p < 0.001). Corneal astigmatism was greater and the central cornea was thinner in MFS eyes (530.14 ± 41.31 μm versus 547.02 ± 39.18 μm, p < 0.001). MFS eyes were more myopic than control eyes (spherical equivalent -2.16 ± 3.75 D versus -1.17 ± 2.58 D, p < 0.001). Visual acuity was reduced (0.13 ± 0.25 logMAR versus 0.05 ± 0.18 logMAR, p < 0.001) and intraocular pressure was lower in MFS eyes (14.6 ± 3.4 mmHg versus 15.1 ± 3.2 mmHg, p = 0.01). Iris transillumination defects (ITD) were significantly more common in MFS eyes (odds ratio for MFS in the presence of ITD, 3.7). Ectopia lentis (EL) was only present in MFS eyes (33.4%). History of retinal detachment was significantly more common in MFS eyes. Glaucoma was equally common in both groups. Conclusions ITD and EL are most characteristic findings in MFS. ITD and corneal curvature should be studied as diagnostic criteria for MFS. Visual acuity is reduced in MFS. MFS patients need regular eye exams to identify serious ocular complications. PMID:28931008

  18. Structural constraints in the packaging of bluetongue virus genomic segments

    OpenAIRE

    Burkhardt, Christiane; Sung, Po-Yu; Celma, Cristina C.; Roy, Polly

    2014-01-01

    : The mechanism used by bluetongue virus (BTV) to ensure the sorting and packaging of its 10 genomic segments is still poorly understood. In this study, we investigated the packaging constraints for two BTV genomic segments from two different serotypes. Segment 4 (S4) of BTV serotype 9 was mutated sequentially and packaging of mutant ssRNAs was investigated by two newly developed RNA packaging assay systems, one in vivo and the other in vitro. Modelling of the mutated ssRNA followed by bioche...

  19. Development of a Colloidal Gold Kit for the Diagnosis of Severe Fever with Thrombocytopenia Syndrome Virus Infection

    Directory of Open Access Journals (Sweden)

    Xianguo Wang

    2014-01-01

    Full Text Available It is critical to develop a cost-effective detection kit for rapid diagnosis and on-site detection of severe fever with thrombocytopenia syndrome virus (SFTSV infection. Here, an immunochromatographic assay (ICA to detect SFTSV infection is described. The ICA uses gold nanoparticles coated with recombinant SFTSV for the simultaneous detection of IgG and IgM antibodies to SFTSV. The ICA was developed and evaluated by using positive sera samples of SFTSV infection (n=245 collected from the CDC of China. The reference laboratory diagnosis of SFTSV infection was based on the “gold standard”. The results demonstrated that the positive coincidence rate and negative coincidence rate were determined to be 98.4% and 100% for IgM and 96.7% and 98.6% for IgG, respectively. The kit showed good selectivity for detection of SFTSV-specific IgG and IgM with no interference from positive sera samples of Japanese encephalitis virus infection, Dengue virus infection, Hantavirus infection, HIV infection, HBV surface antigen, HCV antibody, Mycobacterium tuberculosis antibody, or RF. Based on these results, the ICS test developed may be a suitable tool for rapid on-site testing for SFTSV infections.

  20. The assessment of efficacy of porcine reproductive respiratory syndrome virus inactivated vaccine based on the viral quantity and inactivation methods

    Directory of Open Access Journals (Sweden)

    Lee Byeongchun

    2011-06-01

    Full Text Available Abstract Background There have been many efforts to develop efficient vaccines for the control of porcine reproductive and respiratory syndrome virus (PRRSV. Although inactivated PRRSV vaccines are preferred for their safety, they are weak at inducing humoral immune responses and controlling field PRRSV infection, especially when heterologous viruses are involved. Results In all groups, the sample to positive (S/P ratio of IDEXX ELISA and the virus neutralization (VN titer remained negative until challenge. While viremia did not reduce in the vaccinated groups, the IDEXX-ELISA-specific immunoglobulin G increased more rapidly and to significantly greater levels 7 days after the challenge in all the vaccinated groups compared to the non-vaccinated groups (p 6 PFU/mL PRRSV vaccine-inoculated and binary ethylenimine (BEI-inactivated groups 22 days after challenge (p Conclusions The inactivated vaccine failed to show the humoral immunity, but it showed different immune response after the challenge compared to mock group. Although the 106 PFU/mL-vaccinated and BEI-inactivated groups showed significantly greater VN titers 22 days after challenge, all the groups were already negative for viremia.

  1. Zika virus infection and Guillain-Barré syndrome: a review focused on clinical and electrophysiological subtypes.

    Science.gov (United States)

    Uncini, Antonino; Shahrizaila, Nortina; Kuwabara, Satoshi

    2017-03-01

    In 2016, we have seen a rapid emergence of Zika virus-associated Guillain-Barré syndrome (GBS) since its first description in a French-Polynesian patient in 2014. Current evidence estimates the incidence of GBS at 24 cases per 100 000 persons infected by Zika virus. This will result in a sharp rise in the number of GBS cases worldwide with the anticipated global spread of Zika virus. A better understanding of the pathogenesis of Zika-associated GBS is crucial to prepare us for the current epidemic. In this review, we evaluate the existing literature on GBS in association with Zika and other flavivirus to better define its clinical subtypes and electrophysiological characteristics, demonstrating a demyelinating subtype of GBS in most cases. We also recommend measures that will help reduce the gaps in knowledge that currently exist. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. Assessing Virulence and Transmission Rates of White Spot Syndrome Virus (WSSV) in Two Ecologically Important Palaemonid Shrimp

    Science.gov (United States)

    Bernard, C.; Keesee, B.; Philippoff, C.; Curran, S.; Lotz, J.; Powell, E.

    2016-02-01

    Investigators, including three REU interns, conducted an experiment to quantify parameters for an epidemiological model designed to estimate disease transmission in marine invertebrates. White spot syndrome virus (WSSV) is a highly pathogenic disease affecting commercially important penaeid shrimp fisheries worldwide. The virus devastates penaeid shrimp but other varieties of decapods may serve as reservoirs for disease by being less susceptible to WSSV or refractory to disease. Non-penaeid crustaceans are less susceptible to WSSV, and different species have variable resistance to the disease leading to different potential to serve as reservoirs for transmission of the disease to coastal penaeid fisheries. This study investigates virulence and transmission rates of WSSV in two palaemonid shrimp which are keystone members of coastal food webs, and effects of species interactions on transmission rates of WSSV are estimated in a laboratory setting as a proxy for natural habitats. Two species of grass shrimp were exposed to a Chinese strain of WSSV through feeding the test individuals with previously prepared, inoculated penaeid shrimp. Replicated tanks containing 30 animals were exposed to the virus in arenas containing one or both species for 24 hours, then isolated in 1 liter tanks and monitored. During the isolation period moribund individuals were preserved for later analysis. After 7 days all test individuals were analyzed using qPCR to determine WSSV presence and load in DNA. From these data transmission rates, mortality, and viral concentration were quantified and used as parameters in a simple epidemiological model.

  3. Structure and behaviour of proteins, nucleic acids and viruses from vibrational Raman optical activity

    DEFF Research Database (Denmark)

    Barron, L.D.; Blanch, E.W.; McColl, I.H.

    2003-01-01

    stacking arrangement and the mutual orientation of the sugar and base rings around the C-N glycosidic link. The ROA spectra of intact viruses provide information on the folds of the coat proteins and the nucleic acid structure. The large number of structure-sensitive bands in protein ROA spectra...... is especially favourable for fold determination using pattern recognition techniques. This article gives a brief account of the ROA technique and presents the ROA spectra of a selection of proteins, nucleic acids and viruses that illustrate the applications of ROA spectroscopy in biomolecular research....

  4. Structure of a trimeric variant of the Epstein-Barr virus glycoprotein B

    Energy Technology Data Exchange (ETDEWEB)

    Backovic, Marija [Northwestern Univ., Evanston, IL (United States); Longnecker, Richard [Northwestern Univ., Chicago, IL (United States); Jardetzky, Theodore S [Northwestern Univ., Evanston, IL (United States)

    2009-03-16

    Epstein-Barr virus (EBV) is a herpesvirus that is associated with development of malignancies of lymphoid tissue. EBV infections are life-long and occur in >90% of the population. Herpesviruses enter host cells in a process that involves fusion of viral and cellular membranes. The fusion apparatus is comprised of envelope glycoprotein B (gB) and a heterodimeric complex made of glycoproteins H and L. Glycoprotein B is the most conserved envelope glycoprotein in human herpesviruses, and the structure of gB from Herpes simplex virus 1 (HSV-1) is available. Here, we report the crystal structure of the secreted EBV gB ectodomain, which forms 16-nm long spike-like trimers, structurally homologous to the postfusion trimers of the fusion protein G of vesicular stomatitis virus (VSV). Comparative structural analyses of EBV gB and VSV G, which has been solved in its pre and postfusion states, shed light on gB residues that may be involved in conformational changes and membrane fusion. Also, the EBV gB structure reveals that, despite the high sequence conservation of gB in herpesviruses, the relative orientations of individual domains, the surface charge distributions, and the structural details of EBV gB differ from the HSV-1 protein, indicating regions and residues that may have important roles in virus-specific entry.

  5. Epstein-Barr virus-containing T-cell lymphoma presents with hemophagocytic syndrome mimicking malignant histiocytosis.

    Science.gov (United States)

    Su, I J; Hsu, Y H; Lin, M T; Cheng, A L; Wang, C H; Weiss, L M

    1993-09-15

    The previously designated malignant histiocytosis (MH) may include lymphoid neoplasms of T-cell lineage as well as patients with benign virus-associated hemophagocytic syndrome (VAHS). In this study, the association of Epstein-Barr virus (EBV) with T cell lymphomas which present with clinicopathologic features indistinguishable from malignant histiocytosis (MH) was investigated further. Four adult patients, three women and one man, were admitted because of fever, cutaneous lesions, hepatosplenomegaly, and jaundice. Laboratory examinations revealed pancytopenia, abnormal liver functions and coagulopathy. All patients ran a fulminant course terminating in a hemophagocytic syndrome within 1 month. Immunophenotypic study, Southern blot analysis, and in situ hybridization were performed on the specimens obtained from the four patients. The biopsy-necropsy specimens from skin, liver, spleen, and bone marrow showed infiltration of atypical large cells with reactive histiocytosis and florid hemophagocytosis activity. Based on the clinical and histologic findings, these cases would have been designated as MH by previous criteria. Immunophenotypic, Southern blot, and in situ hybridization studies, however, showed clonotypic proliferation of EBV genomes in the nuclei of the large atypical cells that expressed T-cell antigens. Therefore, these patients should be diagnosed as a recently described EBV-associated peripheral T-cell lymphoma (EBV-PTCL). EBV-PTCL may present with a fulminant hemophagocytic syndrome indistinguishable from the previously designated MH. This finding represents a step forward in our changing concept regarding MH, some of which only recently has been suggested to be of T-cell lymphoma origin. Differentiation from benign VAHS is clinically important. Features useful in this distinction are tabulated and discussed.

  6. Effect of three innovative culture systems on water quality and whitespot syndrome virus (WSSV) viral load in WSSV-fed Penaeus monodon cultured in indoor tanks

    NARCIS (Netherlands)

    Alapide-Tendencia, E.V.; Bosma, R.H.; Rose Sorio, L.

    2012-01-01

    White spot syndrome virus is the most important among the shrimp diseases. It has been devastating the shrimp industry for more than 3 decades. Previous studies reported that greater percentage of yellow colonies on thiosulfate citrate bile salt sucrose agar (yellow vibrios) in the rearing water,

  7. Interferon alpha inhibits viral replication of a live-attenuated porcine reproductive and respiratory syndrome virus vaccine preventing development of an adaptive immune response in swine

    Science.gov (United States)

    Type I interferons, such as interferon alpha (IFNa), contribute to innate antiviral immunity by promoting production of antiviral mediators and are also involved in promoting an adaptive immune response. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating and c...

  8. Mycoplasma pneumoniae preceding Lemierre's syndrome due to Fusobacterium nucleatum complicated by acute Epstein-Barr virus (EBV) infectious mononucleosis in an immunocompetent host.

    Science.gov (United States)

    Klein, Natalie C; Petelin, Andrew; Cunha, Burke A

    2013-01-01

    We report an unusual case of Lemierre's syndrome due to a rare species of Fusobacterium, that is, Fusobacterium nucleatum preceded by Mycoplasma pneumoniae pharyngitis and followed later by Epstein-Barr virus infectious mononucleosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. High Incidence of Recurrent Wheeze in Children With Down Syndrome With and Without Previous Respiratory Syncytial Virus Lower Respiratory Tract Infection

    NARCIS (Netherlands)

    Bloemers, B.; van Furth, A.M.; Weijerman, M.E.; Gemke, R.J.B.J.; Broers, C.J.M.; Kimpen, J.L.L.; Bont, L.

    2010-01-01

    Background: Respiratory syncytial virus (RSV)-induced lower respiratory tract infection (LRTI) is associated with the subsequent development of recurrent wheeze. In a recent study, we found a high incidence (9.9%) of hospitalization for RSV-induced LRTI among children with Down syndrome (DS),

  10. Indel-II region deletion sizes in the white spot syndrome virus genome correlate with shrimp disease outbreaks in southern Vietnam

    NARCIS (Netherlands)

    Tran Thi Tuyet, H.; Zwart, M.P.; Phuong, N.T.; Oanh, D.T.H.; Jong, de M.C.M.; Vlak, J.M.

    2012-01-01

    Sequence comparisons of the genomes of white spot syndrome virus (WSSV) strains have identified regions containing variable-length insertions/deletions (i.e. indels). Indel-I and Indel-II, positioned between open reading frames (ORFs) 14/15 and 23/24, respectively, are the largest and the most

  11. Transmission of white spot syndrome virus in improved-extensive and semi-intensive shrimp production systems: A molecular epidemiology study

    NARCIS (Netherlands)

    Tuyet Hoa, T.T.; Zwart, M.P.; Phuong, N.T.; Vlak, J.M.; Jong, de M.C.M.

    2011-01-01

    Experimental evidence suggests that white spot syndrome virus (WSSV) can be transmitted horizontally through water, via carrier organisms and/or by cannibalism of infected shrimp, but also vertically through infected broodstock. However the mode(s) of WSSV transmission in shrimp farming systems and

  12. Low numbers of repeat units in variable number of tandem repeats (VNTR) regions of white spot syndrome virus are correlated with disease outbreaks

    NARCIS (Netherlands)

    Tran Thi Tuyet, H.; Zwart, M.P.; Phuong, N.T.; Jong, de M.C.M.; Vlak, J.M.

    2012-01-01

    White spot syndrome virus (WSSV) is the most important pathogen in shrimp farming systems worldwide including the Mekong Delta, Vietnam. The genome of WSSV is characterized by the presence of two major 'indel regions' found at ORF14/15 and ORF23/24 (WSSV-Thailand) and three regions with variable

  13. Analysis of ORF 1 in European porcine reproductive and respiratory syndrome virus by long RT-PCR and restriction fragment length polymorphism (RFLP) analysis

    DEFF Research Database (Denmark)

    Nielsen, H. S.; Storgaard, Torben; Oleksiewicz, M.B.

    2000-01-01

    A rapid method was developed for partial characterization of the replicase-encoding open reading frame 1 (ORF 1) of porcine reproductive and respiratory syndrome virus (PRRSV). It comprised long RT-PCR amplification of 11.1 kb (94%) of ORF 1, followed by restriction fragment length polymorphism a...

  14. Hashimoto's Thyroiditis Presenting as Acute Painful Thyroiditis and as a Manifestation of an Immune Reconstitution Inflammatory Syndrome in a Human Immunodeficiency Virus-Seropositive Patient.

    NARCIS (Netherlands)

    Visser, R.; Mast, Q. de; Netea-Maier, R.T.; Ven, A.J.A.M. van der

    2012-01-01

    Background: An immune reconstitution inflammatory syndrome (IRIS) may complicate immune restoration following start of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients. The occurrence of Graves' disease in the setting of an IRIS is well recognized. We hereby

  15. Yeast Surface Display of Two Proteins Previously Shown to Be Protective Against White Spot Syndrome Virus (WSSV) in Shrimp.

    Science.gov (United States)

    Ananphongmanee, Vorawit; Srisala, Jiraporn; Sritunyalucksana, Kallaya; Boonchird, Chuenchit

    2015-01-01

    Cell surface display using the yeasts Saccharomyces cerevisiae and Pichia pastoris has been extensively developed for application in bioindustrial processes. Due to the rigid structure of their cell walls, a number of proteins have been successfully displayed on their cell surfaces. It was previously reported that the viral binding protein Rab7 from the giant tiger shrimp Penaeus monodon (PmRab7) and its binding partner envelope protein VP28 of white spot syndrome virus (WSSV) could independently protect shrimp against WSSV infection. Thus, we aimed to display these two proteins independently on the cell surfaces of 2 yeast clones with the ultimate goal of using a mixture of the two clones as an orally deliverable, antiviral agent to protect shrimp against WSSV infection. PmRab7 and VP28 were modified by N-terminal tagging to the C-terminal half of S. cerevisiae α-agglutinin. DNA fragments, harboring fused-gene expression cassettes under control of an alcohol oxidase I (AOX1) promoter were constructed and used to transform the yeast cells. Immunofluorescence microscopy with antibodies specific to both proteins demonstrated that mutated PmRab7 (mPmRab7) and partial VP28 (pVP28) were localized on the cell surfaces of the respective clones, and fluorescence intensity for each was significantly higher than that of control cells by flow cytometry. Enzyme-linked immunosorbant assay (ELISA) using cells displaying mPmRab7 or pVP28 revealed that the binding of specific antibodies for each was dose-dependent, and could be saturated. In addition, the binding of mPmRab7-expressing cells with free VP28, and vice versa was dose dependent. Binding between the two surface-expressed proteins was confirmed by an assay showing agglutination between cells expressing complementary mPmRab7 and pVP28. In summary, our genetically engineered P. pastoris can display biologically active mPmRab7 and pVP28 and is now ready for evaluation of efficacy in protecting shrimp against WSSV by oral

  16. Yeast Surface Display of Two Proteins Previously Shown to Be Protective Against White Spot Syndrome Virus (WSSV in Shrimp.

    Directory of Open Access Journals (Sweden)

    Vorawit Ananphongmanee

    Full Text Available Cell surface display using the yeasts Saccharomyces cerevisiae and Pichia pastoris has been extensively developed for application in bioindustrial processes. Due to the rigid structure of their cell walls, a number of proteins have been successfully displayed on their cell surfaces. It was previously reported that the viral binding protein Rab7 from the giant tiger shrimp Penaeus monodon (PmRab7 and its binding partner envelope protein VP28 of white spot syndrome virus (WSSV could independently protect shrimp against WSSV infection. Thus, we aimed to display these two proteins independently on the cell surfaces of 2 yeast clones with the ultimate goal of using a mixture of the two clones as an orally deliverable, antiviral agent to protect shrimp against WSSV infection. PmRab7 and VP28 were modified by N-terminal tagging to the C-terminal half of S. cerevisiae α-agglutinin. DNA fragments, harboring fused-gene expression cassettes under control of an alcohol oxidase I (AOX1 promoter were constructed and used to transform the yeast cells. Immunofluorescence microscopy with antibodies specific to both proteins demonstrated that mutated PmRab7 (mPmRab7 and partial VP28 (pVP28 were localized on the cell surfaces of the respective clones, and fluorescence intensity for each was significantly higher than that of control cells by flow cytometry. Enzyme-linked immunosorbant assay (ELISA using cells displaying mPmRab7 or pVP28 revealed that the binding of specific antibodies for each was dose-dependent, and could be saturated. In addition, the binding of mPmRab7-expressing cells with free VP28, and vice versa was dose dependent. Binding between the two surface-expressed proteins was confirmed by an assay showing agglutination between cells expressing complementary mPmRab7 and pVP28. In summary, our genetically engineered P. pastoris can display biologically active mPmRab7 and pVP28 and is now ready for evaluation of efficacy in protecting shrimp against

  17. Structure of the acidianus filamentous virus 3 and comparative genomics of related archaeal lipothrixviruses

    DEFF Research Database (Denmark)

    Vestergaard, Gisle Alberg; Aramayo, Ricardo; Basta, Tamara

    2008-01-01

    Four novel filamentous viruses with double-stranded DNA genomes, namely, Acidianus filamentous virus 3 (AFV3), AFV6, AFV7, and AFV8, have been characterized from the hyperthermophilic archaeal genus Acidianus, and they are assigned to the Betalipothrixvirus genus of the family Lipothrixviridae....... The structures of the approximately 2-mum-long virions are similar, and one of them, AFV3, was studied in detail. It consists of a cylindrical envelope containing globular subunits arranged in a helical formation that is unique for any known double-stranded DNA virus. The envelope is 3.1 nm thick and encases...... structural proteins; (iii) multiple overlapping open reading frames, which may be indicative of gene recoding; (iv) putative 12-bp genetic elements; and (v) partial gene sequences corresponding closely to spacer sequences of chromosomal repeat clusters....

  18. Structure, morphogenesis and function of tubular structures induced by cowpea mosaic virus

    NARCIS (Netherlands)

    Kasteel, D.T.J.

    1999-01-01

    During systemic plant infection, viruses move from the initially infected cells through plasmodesmata to neighbouring cells. Different mechanisms have been proposed for this cell-to-cell movement. Cowpea mosaic virus (CPMV) employs one of the major movement mechanisms, i.e. tubule-guided

  19. The small envelope protein of porcine reproductive and respiratory syndrome virus possesses ion channel protein-like properties

    International Nuclear Information System (INIS)

    Lee, Changhee; Yoo, Dongwan

    2006-01-01

    The small envelope (E) protein of porcine reproductive and respiratory syndrome virus (PRRSV) is a hydrophobic 73 amino acid protein encoded in the internal open reading frame (ORF) of the bicistronic mRNA2. As a first step towards understanding the biological role of E protein during PRRSV replication, E gene expression was blocked in a full-length infectious clone by mutating the ATG translational initiation to GTG, such that the full-length mutant genomic clone was unable to synthesize the E protein. DNA transfection of PRRSV-susceptible cells with the E gene knocked-out genomic clone showed the absence of virus infectivity. P129-ΔE-transfected cells however produced virion particles in the culture supernatant, and these particles contained viral genomic RNA, demonstrating that the E protein is essential for PRRSV infection but dispensable for virion assembly. Electron microscopy suggests that the P129-ΔE virions assembled in the absence of E had a similar appearance to the wild-type particles. Strand-specific RT-PCR demonstrated that the E protein-negative, non-infectious P129-ΔE virus particles were able to enter cells but further steps of replication were interrupted. The entry of PRRSV has been suggested to be via receptor-mediated endocytosis, and lysomotropic basic compounds and known ion-channel blocking agents both inhibited PRRSV replication effectively during the uncoating process. The expression of E protein in Escherichia coli-mediated cell growth arrests and increased the membrane permeability. Cross-linking experiments in cells infected with PRRSV or transfected with E gene showed that the E protein was able to form homo-oligomers. Taken together, our data suggest that the PRRSV E protein is likely an ion-channel protein embedded in the viral envelope and facilitates uncoating of virus and release of the genome in the cytoplasm

  20. Doped titanium oxide photcatalysts: Preparation, structure and interaction with viruses

    Science.gov (United States)

    Li, Qi

    Since the discovery of photoelectrochemical splitting of water on n-titanium oxide (n-TiO2) electrodes by Fujishima and Honda in 1972, there has been much interest in semiconductor-based materials as photocatalysts for both solar energy conversion and environmental applications in the past several decades. Among various semiconductor-based photocatalysts, TiO2 is the only candidate suitable for industrial use because of its high chemical stability, good photoactivity, relatively low cost, and nontoxicity. However, the photocatalytic capability of TiO 2 is limited to only ultraviolet (UV) light (wavelength, lambda, strategy to use atomic force microscope (AFM) to conduct in-situ observation of viruses on semiconductor surfaces in aqueous environment was developed, which combines information from both height profile and phase profile and solves the difficulty of observing small nanosized biomolecules on substrates with similar feature sizes.

  1. Structural and antigenic variation among diverse clade 2 H5N1 viruses.

    Directory of Open Access Journals (Sweden)

    David A Shore

    Full Text Available Antigenic variation among circulating H5N1 highly pathogenic avian influenza A viruses mandates the continuous production of strain-specific pre-pandemic vaccine candidates and represents a significant challenge for pandemic preparedness. Here we assessed the structural, antigenic and receptor-binding properties of three H5N1 HPAI virus hemagglutinins, which were recently selected by the WHO as vaccine candidates [A/Egypt/N03072/2010 (Egypt10, clade 2.2.1, A/Hubei/1/2010 (Hubei10, clade 2.3.2.1 and A/Anhui/1/2005 (Anhui05, clade 2.3.4]. These analyses revealed that antigenic diversity among these three isolates was restricted to changes in the size and charge of amino acid side chains at a handful of positions, spatially equivalent to the antigenic sites identified in H1 subtype viruses circulating among humans. All three of the H5N1 viruses analyzed in this study were responsible for fatal human infections, with the most recently-isolated strains, Hubei10 and Egypt10, containing multiple residues in the receptor-binding site of the HA, which were suspected to enhance mammalian transmission. However, glycan-binding analyses demonstrated a lack of binding to human α2-6-linked sialic acid receptor analogs for all three HAs, reinforcing the notion that receptor-binding specificity contributes only partially to transmissibility and pathogenesis of HPAI viruses and suggesting that changes in host specificity must be interpreted in the context of the host and environmental factors, as well as the virus as a whole. Together, our data reveal structural linkages with phylogenetic and antigenic analyses of recently emerged H5N1 virus clades and should assist in interpreting the significance of future changes in antigenic and receptor-binding properties.

  2. Structure and Function of the Non-Structural Protein of Dengue Virus and its Applications in Antiviral Therapy.

    Science.gov (United States)

    Xie, Qian; Zhang, Bao; Yu, JianHai; Wu, Qinghua; Yang, Fangji; Cao, Hong; Zhao, Wei

    2017-01-01

    Dengue fever, a type of global and tropical infectious disease, and its prevention has become a challenging issue worldwide. Antibody-dependent enhancement effects and the virus pathogenic mechanism have not yet been fully elucidated, hindering the development of dengue fever prevention and suitable drug treatment. There is currently no specific prevention and therapy in clinical trials, however, in recent years, studies have focused on the pathogenesis and treatment of dengue. Research focusing on dengue virus nonstructural protein in special drugs for the prevention and control of dengue fever is a new progress leading to improved understanding regarding the prevention and control of dengue fever and suitable drugs for the treatment. The main challenges regarding the structure of dengue virus nonstructural protein and the drugs for antiviral therapy are summarized in this paper.

  3. The first human infection with severe fever with thrombocytopenia syndrome virus in Shaanxi Province, China

    Directory of Open Access Journals (Sweden)

    Jing Wei

    2015-06-01

    Conclusions: SFTSV readily infects humans with outdoor exposure. The results of the serological study indicate that the virus circulates widely in Shaanxi Province. SFTSV represents a public health threat in China.

  4. Experimental inoculation of late term pregnant sows with a field isolate of porcine reproductive and respiratory syndrome vaccine-derived virus

    DEFF Research Database (Denmark)

    Nielsen, Jens; Bøtner, Anette; Bille-Hansen, Vivi

    2002-01-01

    The use of a live attenuated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in piglets has been associated with reproductive disorders in non-vaccinated sows. Vaccine-derived virus (VDV) has been isolated from foctuses, stillborn pigs, and dead: piglets, indicating that the l......The use of a live attenuated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in piglets has been associated with reproductive disorders in non-vaccinated sows. Vaccine-derived virus (VDV) has been isolated from foctuses, stillborn pigs, and dead: piglets, indicating...... than 99.6% identity to the attenuated vaccine virus, originated from the lungs of a stillborn pig from a swine herd with a sudden high level of stillborn pigs and increased piglet mortality in the nursing period. Intranasal inoculation of sows with the virus isolate resulted in congenital infection......, foetal death, and preweaning pig mortality. As such, the present study showed that vaccine-derived PRRSV can cause disease in swine consistent with PRRS....

  5. Transmission dynamics of the recently-identified BYD virus causing duck egg-drop syndrome.

    Directory of Open Access Journals (Sweden)

    Naveen K Vaidya

    Full Text Available Baiyangdian (BYD virus is a recently-identified mosquito-borne flavivirus that causes severe disease in ducks, with extremely rapid transmission, up to 15% mortality within 10 days and 90% reduction in egg production on duck farms within 5 days of infection. Because of the zoonotic nature of flaviviruses, the characterization of BYD virus and its epidemiology are important public health concerns. Here, we develop a mathematical model for the transmission dynamics of this novel virus. We validate the model against BYD outbreak data collected from duck farms in Southeast China, as well as experimental data obtained from an animal facility. Based on our model, the basic reproductive number of BYD virus is high (R(0 = 21 indicating that this virus is highly transmissible, consistent with the dramatic epidemiology observed in BYDV-affected duck farms. Our results indicate that younger ducks are more vulnerable to BYD disease and that ducks infected with BYD virus reduce egg production (to about 33% on average for about 3 days post-infection; after 3 days infected ducks are no longer able to produce eggs. Using our model, we predict that control measures which reduce contact between mosquitoes and ducks such as mosquito nets are more effective than insecticides.

  6. Mud crab susceptibility to disease from white spot syndrome virus is species-dependent

    Directory of Open Access Journals (Sweden)

    Sritunyalucksana Kallaya

    2010-11-01

    Full Text Available Abstract Background Based on a report for one species (Scylla serrata, it is widely believed that mud crabs are relatively resistant to disease caused by white spot syndrome virus (WSSV. We tested this hypothesis by determining the degree of susceptibility in two species of mud crabs, Scylla olivacea and Scylla paramamosain, both of which were identified by mitochondrial 16 S ribosomal gene analysis. We compared single-dose and serial-dose WSSV challenges on S. olivacea and S. paramamosain. Findings In a preliminary test using S. olivacea alone, a dose of 1 × 106 WSSV copies/g gave 100% mortality within 7 days. In a subsequent test, 17 S. olivacea and 13 S. paramamosain were divided into test and control groups for challenge with WSSV at 5 incremental, biweekly doses starting from 1 × 104 and ending at 5 × 106 copies/g. For 11 S. olivacea challenged, 3 specimens died at doses between 1 × 105 and 5 × 105 copies/g and none died for 2 weeks after the subsequent dose (1 × 106 copies/g that was lethal within 7 days in the preliminary test. However, after the final challenge on day 56 (5 × 106 copies/g, the remaining 7 of 11 S. olivacea (63.64% died within 2 weeks. There was no mortality in the buffer-injected control crabs. For 9 S. paramamosain challenged in the same way, 5 (55.56% died after challenge doses between 1 × 104 and 5 × 105 copies/g, and none died for 2 weeks after the challenge dose of 1 × 106 copies/g. After the final challenge (5 × 106 copies/g on day 56, no S. paramamosain died during 2 weeks after the challenge, and 2 of 9 WSSV-infected S. paramamosain (22.22% remained alive together with the control crabs until the end of the test on day 106. Viral loads in these survivors were low when compared to those in the moribund crabs. Conclusions S. olivacea and S. paramamosain show wide variation in response to challenge with WSSV. S. olivacea and S. paramamosain are susceptible to white spot disease, and S. olivacea is more

  7. Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome.

    Science.gov (United States)

    Worbe, Yulia; Marrakchi-Kacem, Linda; Lecomte, Sophie; Valabregue, Romain; Poupon, Fabrice; Guevara, Pamela; Tucholka, Alan; Mangin, Jean-François; Vidailhet, Marie; Lehericy, Stephane; Hartmann, Andreas; Poupon, Cyril

    2015-02-01

    Gilles de la Tourette syndrome is a childhood-onset syndrome characterized by the presence and persistence of motor and vocal tics. A dysfunction of cortico-striato-pallido-thalamo-cortical networks in this syndrome has been supported by convergent data from neuro-pathological, electrophysiological as well as structural and functional neuroimaging studies. Here, we addressed the question of structural integration of cortico-striato-pallido-thalamo-cortical networks in Gilles de la Tourette syndrome. We specifically tested the hypothesis that deviant brain development in Gilles de la Tourette syndrome could affect structural connectivity within the input and output basal ganglia structures and thalamus. To this aim, we acquired data on 49 adult patients and 28 gender and age-matched control subjects on a 3 T magnetic resonance imaging scanner. We used and further implemented streamline probabilistic tractography algorithms that allowed us to quantify the structural integration of cortico-striato-pallido-thalamo-cortical networks. To further investigate the microstructure of white matter in patients with Gilles de la Tourette syndrome, we also evaluated fractional anisotropy and radial diffusivity in these pathways, which are both sensitive to axonal package and to myelin ensheathment. In patients with Gilles de la Tourette syndrome compared to control subjects, we found white matter abnormalities in neuronal pathways connecting the cerebral cortex, the basal ganglia and the thalamus. Specifically, striatum and thalamus had abnormally enhanced structural connectivity with primary motor and sensory cortices, as well as paracentral lobule, supplementary motor area and parietal cortices. This enhanced connectivity of motor cortex positively correlated with severity of tics measured by the Yale Global Tics Severity Scale and was not influenced by current medication status, age or gender of patients. Independently of the severity of tics, lateral and medial orbito

  8. Zika virus produces noncoding RNAs using a multi-pseudoknot structure that confounds a cellular exonuclease

    International Nuclear Information System (INIS)

    Akiyama, Benjamin M.; Laurence, Hannah M.; University of Colorado, Aurora, CO; University of California, Davis, CA; Massey, Aaron R.

    2016-01-01

    The outbreak of Zika virus (ZIKV) and associated fetal microcephaly mandates efforts to understand the molecular processes of infection. Related flaviviruses produce noncoding subgenomic flaviviral RNAs (sfRNAs) that are linked to pathogenicity in fetal mice. These viruses make sfRNAs by co-opting a cellular exonuclease via structured RNAs called xrRNAs. We found that ZIKV-infected monkey and human epithelial cells, mouse neurons, and mosquito cells produce sfRNAs. The RNA structure that is responsible for ZIKV sfRNA production forms a complex fold that is likely found in many pathogenic flaviviruses. Mutations that disrupt the structure affect exonuclease resistance in vitro and sfRNA formation during infection. The complete ZIKV xrRNA structure clarifies the mechanism of exonuclease resistance and identifies features that may modulate function in diverse flaviviruses.

  9. Crystal structure of AFV3-109, a highly conserved protein from crenarchaeal viruses

    Directory of Open Access Journals (Sweden)

    Quevillon-Cheruel Sophie

    2007-01-01

    Full Text Available Abstract The extraordinary morphologies of viruses infecting hyperthermophilic archaea clearly distinguish them from bacterial and eukaryotic viruses. Moreover, their genomes code for proteins that to a large extend have no related sequences in the extent databases. However, a small pool of genes is shared by overlapping subsets of these viruses, and the most conserved gene, exemplified by the ORF109 of the Acidianus Filamentous Virus 3, AFV3, is present on genomes of members of three viral familes, the Lipothrixviridae, Rudiviridae, and "Bicaudaviridae", as well as of the unclassified Sulfolobus Turreted Icosahedral Virus, STIV. We present here the crystal structure of the protein (Mr = 13.1 kD, 109 residues encoded by the AFV3 ORF 109 in two different crystal forms at 1.5 and 1.3 Å resolution. The structure of AFV3-109 is a five stranded β-sheet with loops on one side and three helices on the other. It forms a dimer adopting the shape of a cradle that encompasses the best conserved regions of the sequence. No protein with a related fold could be identified except for the ortholog from STIV1, whose structure was deposited at the Protein Data Bank. We could clearly identify a well bound glycerol inside the cradle, contacting exclusively totally conserved residues. This interaction was confirmed in solution by fluorescence titration. Although the function of AFV3-109 cannot be deduced directly from its structure, structural homology with the STIV1 protein, and the size and charge distribution of the cavity suggested it could interact with nucleic acids. Fluorescence quenching titrations also showed that AFV3-109 interacts with dsDNA. Genomic sequence analysis revealed bacterial homologs of AFV3-109 as a part of a putative previously unidentified prophage sequences in some Firmicutes.

  10. Structure homology and interaction redundancy for discovering virus-host protein interactions.

    Science.gov (United States)

    de Chassey, Benoît; Meyniel-Schicklin, Laurène; Aublin-Gex, Anne; Navratil, Vincent; Chantier, Thibaut; André, Patrice; Lotteau, Vincent

    2013-10-01

    Virus-host interactomes are instrumental to understand global perturbations of cellular functions induced by infection and discover new therapies. The construction of such interactomes is, however, technically challenging and time consuming. Here we describe an original method for the prediction of high-confidence interactions between viral and human proteins through a combination of structure and high-quality interactome data. Validation was performed for the NS1 protein of the influenza virus, which led to the identification of new host factors that control viral replication.

  11. Structural changes in the liver in metabolic syndrome

    Directory of Open Access Journals (Sweden)

    D. V. Vasendin

    2015-01-01

    Full Text Available Scientifically proven close relationship of nonalcoholic fatty liver disease with development of metabolic syndrome and its individual components involves the conclusion that the target organ in metabolic symptom, even regardless of the severity of obesity, the liver occupies a dominant position, as the body undergoes the first characteristic of non-alcoholic fatty liver disease changes, involving violation of metabolism in the body. Dislipoproteinemia plays an important role in the formation of metabolic syndrome in obesity and other obesity-associated diseases. Altered liver function are the root cause of violations of processes of lipid metabolism and, consequently, abnormal functioning of the liver may be a separate, additional and independent risk factor for development of dyslipidemia and obesity as the main component of the metabolic syndrome.

  12. A Novel Detection Platform for Shrimp White Spot Syndrome Virus Using an ICP11-Dependent Immunomagnetic Reduction (IMR) Assay.

    Science.gov (United States)

    Liu, Bing-Hsien; Lin, Yu-Chen; Ho, Chia-Shin; Yang, Che-Chuan; Chang, Yun-Tsui; Chang, Jui-Feng; Li, Chun-Yuan; Cheng, Cheng-Shun; Huang, Jiun-Yan; Lee, Yen-Fu; Hsu, Ming-Hung; Lin, Feng-Chun; Wang, Hao-Ching; Lo, Chu-Fang; Yang, Shieh-Yueh; Wang, Han-Ching

    2015-01-01

    Shrimp white spot disease (WSD), which is caused by white spot syndrome virus (WSSV), is one of the world's most serious shrimp diseases. Our objective in this study was to use an immunomagnetic reduction (IMR) assay to develop a highly sensitive, automatic WSSV detection platform targeted against ICP11 (the most highly expressed WSSV protein). After characterizing the magnetic reagents (Fe3O4 magnetic nanoparticles coated with anti ICP11), the detection limit for ICP11 protein using IMR was approximately 2 x 10(-3) ng/ml, and the linear dynamic range of the assay was 0.1~1 x 10(6) ng/ml. In assays of ICP11 protein in pleopod protein lysates from healthy and WSSV-infected shrimp, IMR signals were successfully detected from shrimp with low WSSV genome copy numbers. We concluded that this IMR assay targeting ICP11 has potential for detecting the WSSV.

  13. Duck "beak atrophy and dwarfism syndrome" disease complex: Interplay of novel goose parvovirus-related virus and duck circovirus?

    Science.gov (United States)

    Li, P; Li, J; Zhang, R; Chen, J; Wang, W; Lan, J; Xie, Z; Jiang, S

    2018-04-01

    As a newly emerged infectious disease, duck "beak atrophy and dwarfism syndrome (BADS)" disease has caused huge economic losses to waterfowl industry in China since 2015. Novel goose parvovirus-related virus (NGPV) is believed the main pathogen of BADS disease; however, BADS is rarely reproduced by infecting ducks with NGPV alone. As avian circovirus infection causes clinical symptoms similar to BADS, duck circovirus (DuCV) is suspected the minor pathogen of BADS disease. In this study, an investigation was carried out to determine the coinfection of NGPV and DuCV in duck embryos and in ducks with BADS disease. According to our study, the coinfection of emerging NGPV and DuCV was prevalent in East China (Shandong, Jiangsu and Anhui province) and could be vertical transmitted, indicating their cooperative roles in duck BADS disease. © 2018 Blackwell Verlag GmbH.

  14. In Vitro Virucidal and Virustatic Properties of the Crude Extract of Cynodon dactylon against Porcine Reproductive and Respiratory Syndrome Virus

    Science.gov (United States)

    Khonghiran, Oapkun; Kunanoppadol, Suchaya; Potha, Teerapong; Chuammitri, Phongsakorn

    2014-01-01

    The in vitro virustatic and virucidal tests of the crude extract of Cynodon dactylon against infection with porcine reproductive and respiratory syndrome virus (PRRSV), a cause of major devastating pig disease, were described. Crude extract of C. dactylon was prepared for cytotoxicity on tissue-culture cells that were used to measure virustatic and virucidal activities against PRRSV. Crude extract of C. dactylon at 0.78 mg/mL showed no cytotoxicity on the cell line, and at that concentration significantly inhibited replication of PRRSV as early as 24 hours post infection (hpi). C. dactylon also inactivated PRRSV as determined by immunoperoxidase monolayer assay (IPMA) compared to the control experiments. In summary, the present study may be among the earliest studies to describe virustatic and virucidal activities of C. dactylon crude extract against PRRSV in vitro. Extracts of C. dactylon may be useful for PRRSV control and prevention on pig farms. PMID:24744959

  15. Generation of an infectious clone of VR-2332, a highly virulent North American type isolate of porcine reproductive and respiratory syndrome virus

    DEFF Research Database (Denmark)

    Nielsen, H.S.; Liu, G.; Nielsen, Jens

    2003-01-01

    A full-length cDNA clone of the prototypical North American porcine reproductive and respiratory syndrome virus (PRRSV) isolate VR-2332 was assembled in the plasmid vector pOK(12). To rescue infectious virus, capped RNA was transcribed in vitro from the pOK(12) clone and transfected into BHK-21C...... cells. The supernatant from transfected monolayers were serially passaged on Marc-145 cells and porcine pulmonary alveolar macrophages. Infectious PRRSV was recovered on Marc-145 cells as well as porcine pulmonary macrophages; thus, the cloned virus exhibited the same cell tropism as the parental VR......-2332 strain. However, the cloned virus was clearly distinguishable from the parental VR-2332 strain by an engineered marker, a BstZ171 restriction site. The full-length cDNA clone had 11 nucleotide changes, 2 of which affected coding, compared to the parental VR-2332 strain. Additionally...

  16. A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging

    International Nuclear Information System (INIS)

    You, Jae-Hwan; Howell, Gareth; Pattnaik, Asit K.; Osorio, Fernando A.; Hiscox, Julian A.

    2008-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, in common with many other positive strand RNA viruses, encodes a nucleocapsid (N) protein which can localise not only to the cytoplasm but also to the nucleolus in virus-infected cells and cells over-expressing N protein. The dynamic trafficking of positive strand RNA virus nucleocapsid proteins and PRRSV N protein in particular between the cytoplasm and nucleolus is unknown. In this study live imaging of permissive and non-permissive cell lines, in conjunction with photo-bleaching (FRAP and FLIP), was used to investigate the trafficking of fluorescent labeled (EGFP) PRRSV-N protein. The data indicated that EGFP-PRRSV-N protein was not permanently sequestered to the nucleolus and had equivalent mobility to cellular nucleolar proteins. Further the nuclear import of N protein appeared to occur faster than nuclear export, which may account for the observed relative distribution of N protein between the cytoplasm and the nucleolus

  17. Structure of Hepatitis C Virus Polymerase in Complex with Primer-Template RNA

    Energy Technology Data Exchange (ETDEWEB)

    Mosley, Ralph T.; Edwards, Thomas E.; Murakami, Eisuke; Lam, Angela M.; Grice, Rena L.; Du, Jinfa; Sofia, Michael J.; Furman, Philip A.; Otto, Michael J. (Pharmasset); (Emerald)

    2012-08-01

    The replication of the hepatitis C viral (HCV) genome is accomplished by the NS5B RNA-dependent RNA polymerase (RdRp), for which mechanistic understanding and structure-guided drug design efforts have been hampered by its propensity to crystallize in a closed, polymerization-incompetent state. The removal of an autoinhibitory {beta}-hairpin loop from genotype 2a HCV NS5B increases de novo RNA synthesis by >100-fold, promotes RNA binding, and facilitated the determination of the first crystallographic structures of HCV polymerase in complex with RNA primer-template pairs. These crystal structures demonstrate the structural realignment required for primer-template recognition and elongation, provide new insights into HCV RNA synthesis at the molecular level, and may prove useful in the structure-based design of novel antiviral compounds. Additionally, our approach for obtaining the RNA primer-template-bound structure of HCV polymerase may be generally applicable to solving RNA-bound complexes for other viral RdRps that contain similar regulatory {beta}-hairpin loops, including bovine viral diarrhea virus, dengue virus, and West Nile virus.

  18. [Autoimmune syndrome in the tropical spastic paraparesis/myelopathy associated with human T-lymphotropic virus infections].

    Science.gov (United States)

    Domínguez, Martha C; Torres, Miyerlandi; Tamayo, Oscar; Criollo, William; Quintana, Milton; Sánchez, Adalberto; García, Felipe

    2008-12-01

    Previous reports have given evidence that in tropical spastic paraparesis (TSP)/human T-lymphotrophic virus (HTLV-I)-associated myelopathy (HAM), an autoimmune process occurs as part of its pathogenesis. The roles of autoimmunity and the molecular mimicry was evaluated in TSP/HAM patients. Plasma samples were characterized from patients in the Pacific coastal region of Colombia. Thirty-seven were identified as TSP/HAM, 10 were diagnosed with adult T-cell leukemia virus, 22 were asymptomatic carriers but seropositive for HTLV-I and 20 were seronegative and served as negative controls. Plasmatic levels of the following were determined: antinuclear antibody (ANA) levels, anticardiolipine-2 (ACL-2), interferon- (IFN-gamma) and interleukin-4 (IL-4). Using Western blot, the crossreactivity of the seropositive and seronegative samples was evaluated against proteins extracted from several central nervous system components of non infected Wistar rats. The HTLV-I seropositive plasmas were crossreacted with a monoclonal tax (LT4 anti-taxp40) from spinal cord neurons of non infected Wistar rats. Of the TSP/HAM patients, 70.2% were reactive against ANA and 83.8% against ACL-2, in contrast with those ATL and asymptomatic seropositives subjects that were not reactive (P<0.001). Moreover, 70.3% had detectable levels of IFN and 43.2% had detectable IL-4. LT4 anti-taxp40 and plasma of TSP/HAM exhibited cross reactivity with a MW 33-35 kDa protein from the rat spinal cord nuclei. Support was provided for the existence of an autoimmune syndrome mediated by molecular mimicry; the syndrome was responsible for some of the axonal degeneration observed in TSP/HAM patients.

  19. Structural Analysis of Major Species Barriers between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fang (UMM)

    2008-09-23

    It is believed that a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), was passed from palm civets to humans and caused the epidemic of SARS in 2002 to 2003. The major species barriers between humans and civets for SARS-CoV infections are the specific interactions between a defined receptor-binding domain (RBD) on a viral spike protein and its host receptor, angiotensin-converting enzyme 2 (ACE2). In this study a chimeric ACE2 bearing the critical N-terminal helix from civet and the remaining peptidase domain from human was constructed, and it was shown that this construct has the same receptor activity as civet ACE2. In addition, crystal structures of the chimeric ACE2 complexed with RBDs from various human and civet SARS-CoV strains were determined. These structures, combined with a previously determined structure of human ACE2 complexed with the RBD from a human SARS-CoV strain, have revealed a structural basis for understanding the major species barriers between humans and civets for SARS-CoV infections. They show that the major species barriers are determined by interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479 and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced salt bridges at the hydrophobic virus/receptor interface, and that SARS-CoV has evolved to gain sustained infectivity for human cells by eliminating unfavorable free charges at the interface through stepwise mutations at positions 479 and 487. These results enhance our understanding of host adaptations and cross-species infections of SARS-CoV and other emerging animal viruses.

  20. The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis

    Science.gov (United States)

    Stiasny, Karin

    2017-01-01

    SUMMARY Zika virus was discovered ∼70 years ago in Uganda and maintained a low profile as a human disease agent in Africa and Asia. Only recently has it caused explosive outbreaks in previously unaffected regions, first in Oceania and then in the Americas since 2015. Of special concern is the newly identified link between congenital malformations (especially microcephaly) and Zika virus infections during pregnancy. At present, it is unclear whether Zika virus changed its pathogenicity or whether the huge number of infections allowed the recognition of a previously cryptic pathogenic property. The purpose of this review is to discuss recent data on the molecular antigenic structure of Zika virus in the context of antibody-mediated neutralization and antibody-dependent enhancement (ADE) of infection, a phenomenon that has been implicated in the development of severe disease caused by the related dengue viruses. Emphasis is given to epitopes of antibodies that potently neutralize Zika virus and also to epitopes that provide antigenic links to other important human-pathogenic flaviviruses such as dengue, yellow fever, West Nile, Japanese encephalitis, and tick-borne encephalitis viruses. The antigenic cross talk between Zika and dengue viruses appears to be of special importance, since they cocirculate in many regions of endemicity and sequential infections are likely to occur frequently. New insights into the molecular antigenic structure of Zika virus and flaviviruses in general have provided the foundation for great progress made in developing Zika virus vaccines and antibodies for passive immunization. PMID:28179396

  1. Structural and Functional Studies on the Fusion and Attachment Envelope Glycoproteins of Nipah Virus and Hendra Virus

    National Research Council Canada - National Science Library

    Bossart, Katharine

    2003-01-01

    Nipah virus (NiV) and Hendra (HeV) virus are emerging, biosafety level 4 paramyxoviruses responsible for fatal zoonotic infections of humans from pigs and horses, respectively, and are the prototypic members of a new Paramyxovirinae...

  2. The human immunodeficiency virus preventive vaccine research at the French National Agency for acquired immunodeficiency syndrome research

    Directory of Open Access Journals (Sweden)

    Elizabeth Fischer

    2005-02-01

    Full Text Available The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS epidemic is of unprecedented gravity and is spreading rapidly, notably in the most disadvantaged regions of the world. The search for a preventive vaccine is thus an absolute priority. For over 10 years the French National Agency for AIDS research (ANRS has been committed to an original program combining basic science and clinical research. The HIV preventive vaccine research program run by the ANRS covers upstream research for the definition of immunogens, animal models, and clinical research to evaluate candidate vaccines. Most researchers in 2004 believe that it should be possible to obtain partial vaccine protection through the induction of a strong and multiepitopic cellular response. Since 1992, the ANRS has set up 15 phases I and II clinical trials in order to evaluate the safety and the capacity of the candidate vaccines for inducing cellular immune responses. The tested candidate vaccines were increasingly complex recombinant canarypox viruses (Alvac containing sequences coding for certain viral proteins, utilized alone or combined with other immunogens (whole or truncated envelope proteins. ANRS has also been developing an original strategy based on the utilization of lipopeptides. These comprise synthetic fragments of viral proteins associated with lipids that facilitate the induction of a cellular immune response. These approaches promptly allowed the assessment of a prime-boost strategy combining a viral vector and lipopeptides.

  3. Risk factors associated with white spot syndrome virus infection in a Vietnamese rice-shrimp farming system.

    Science.gov (United States)

    Corsin, F; Turnbull, J F; Hao, N V; Mohan, C V; Phi, T T; Phuoc, L H; Tinh, N T; Morgan, K L

    2001-10-29

    White spot disease (WSD) is a pandemic disease caused by a virus commonly known as white spot syndrome virus (WSSV). Several risk factors for WSD outbreaks have been suggested. However, there have been very few studies to identify risk factors for WSD outbreaks in culture systems. This paper presents and discusses the risk factors for WSSV infection identified during a longitudinal observational study conducted in a Vietnamese rice-shrimp farming system. A total of 158 variables were measured comprising location, features of the pond, management practices, pond bottom quality, shrimp health and other animals in the pond. At the end of the study period WSSV was detected in 15 of the 24 ponds followed through the production cycle (62.5%). One hundred and thirty-nine variables were used in univariate analyses. All the variables with a p-value Hemigrapsus spp. crabs during the first month of production, feeding vitamin premix or legumes, presence of high numbers of shrimp with bacterial infection and the presence of larger mud crabs or gobies at harvest. No associations were detected with WSSV at harvest and stocking density, presence, or number or weight of wild shrimp in the pond. The multivariate model to identify outcomes associated with WSSV infection highlighted the presence of high mortality as the main variable explaining the data. The results obtained from this study are discussed in the context of WSD control and areas requiring further investigation are suggested.

  4. Incidence and clinical characteristics of Guillain-Barré syndrome before the introduction of Zika virus in Puerto Rico.

    Science.gov (United States)

    Salinas, Jorge L; Major, Chelsea G; Pastula, Daniel M; Dirlikov, Emilio; Styczynski, Ashley; Luciano, Carlos A; Wojna, Valerie; Sharp, Tyler M; Sejvar, James J; Rivera-Garcia, Brenda

    2017-06-15

    Zika virus has been associated with increases in Guillain-Barré syndrome (GBS) incidence. A GBS incidence estimation and clinical description was performed to assess baseline GBS epidemiology before the introduction of Zika virus in Puerto Rico. Hospitalization administrative data from an island-wide insurance claims database and U.S. Census Bureau population estimates provided a crude GBS incidence for 2013. This estimate was adjusted using the proportion of GBS cases meeting Brighton criteria for confirmed GBS from nine reference hospitals. Characteristics of confirmed GBS cases in the same nine hospitals during 2012-2015 are described. A total of 136 GBS hospitalization claims were filed in 2013 (crude GBS incidence was 3.8 per 100,000 population). The adjusted GBS incidence was 1.7 per 100,000 population. Of 67 confirmed GBS cases during 2012-2015, 66% had an antecedent illness. Median time from antecedent illness to GBS onset was 7days. Most cases (67%) occurred during July-September. Puerto Rico's GBS incidence for 2013 was estimated using a combination of administrative data and medical records review; this method could be employed in other regions to monitor GBS incidence before and after the introduction of GBS infectious triggers. Published by Elsevier B.V.

  5. Microarray and RT-PCR screening for white spot syndrome virus immediate-early genes in cycloheximide-treated shrimp

    International Nuclear Information System (INIS)

    Liu Wangjing; Chang Yunshiang; Wang Chunghsiung; Kou, Guang-Hsiung; Lo Chufang

    2005-01-01

    Here, we report for the first time the successful use of cycloheximide (CHX) as an inhibitor to block de novo viral protein synthesis during WSSV (white spot syndrome virus) infection. Sixty candidate IE (immediate-early) genes were identified using a global analysis microarray technique. RT-PCR showed that the genes corresponding to ORF126, ORF242 and ORF418 in the Taiwan isolate were consistently CHX-insensitive, and these genes were designated ie1, ie2 and ie3, respectively. The sequences for these IE genes also appear in the two other WSSV isolates that have been sequenced. Three corresponding ORFs were identified in the China WSSV isolate, but only an ORF corresponding to ie1 was predicted in the Thailand isolate. In a promoter activity assay in Sf9 insect cells using EGFP (enhanced green fluorescence protein) as a reporter, ie1 showed very strong promoter activity, producing higher EGFP signals than the insect Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV) ie2 promoter

  6. Shrimp miR-12 Suppresses White Spot Syndrome Virus Infection by Synchronously Triggering Antiviral Phagocytosis and Apoptosis Pathways

    Science.gov (United States)

    Shu, Le; Zhang, Xiaobo

    2017-01-01

    Growing evidence has indicated that the innate immune system can be regulated by microRNAs (miRNAs). However, the mechanism underlying miRNA-mediated simultaneous activation of multiple immune pathways remains unknown. To address this issue, the role of host miR-12 in shrimp (Marsupenaeus japonicus) antiviral immune responses was characterized in the present study. The results indicated that miR-12 participated in virus infection, host phagocytosis, and apoptosis in defense against white spot syndrome virus invasion. miR-12 could simultaneously trigger phagocytosis, apoptosis, and antiviral immunity through the synchronous downregulation of the expression of shrimp genes [PTEN (phosphatase and tensin homolog) and BI-1(transmembrane BAX inhibitor motif containing 6)] and the viral gene (wsv024). Further analysis showed that miR-12 could synchronously mediate the 5′–3′ exonucleolytic degradation of its target mRNAs, and this degradation terminated in the vicinity of the 3′ untranslated region sequence complementary to the seed sequence of miR-12. Therefore, the present study showed novel aspects of the miRNA-mediated simultaneous regulation of multiple immune pathways. PMID:28824612

  7. Application of a Label-Free Immunosensor for White Spot Syndrome Virus (WSSV) in Shrimp Cultivation Water.

    Science.gov (United States)

    Waiyapoka, Thanyaporn; Deachamag, Panchalika; Chotigeat, Wilaiwan; Bunsanong, Nittaya; Kanatharana, Proespichaya; Thavarungkul, Panote; Loyprasert-Thananimit, Suchera

    2015-10-01

    White spot syndrome virus (WSSV) is a major pathogen affecting the shrimp industry worldwide. In a preliminary study, WSSV binding protein (WBP) was specifically bound to the VP26 protein of WSSV. Therefore, we have developed the label-free affinity immunosensor using the WBP together with anti-GST-VP26 for quantitative detection of WSSV in shrimp pond water. When the biological molecules were immobilized on a gold electrode to form a self-assembled monolayer, it was then used to detect WSSV using a flow injection system with optimized conditions. Binding between the different copies of WSSV and the immobilized biological molecules was detected by an impedance change (ΔZ″) in real time. The sensitivity of the developed immunosensor was in the linear range of 1.6 × 10(1)-1.6 × 10(6) copies/μl. The system was highly sensitive for the analysis of WSSV as shown by the lack of impedance change when using yellow head virus (YHV). The developed immunosensor could be reused up to 37 times (relative standard deviation (RSD), 3.24 %) with a good reproducibility of residual activity (80-110 %). The immunosensor was simple to operate, reliable, reproducible, and could be applied for the detection and quantification of WSSV in water during shrimp cultivation.

  8. An Elegant Analysis of White Spot Syndrome Virus Using a Graphene Oxide/Methylene Blue based Electrochemical Immunosensor Platform

    Science.gov (United States)

    Natarajan, Anusha; Devi, K. S. Shalini; Raja, Sudhakaran; Senthil Kumar, Annamalai

    2017-04-01

    White spot syndrome virus (WSSV) is a major devastating virus in aquaculture industry. A sensitive and selective diagnostic method for WSSV is a pressing need for the early detection and protection of the aquaculture farms. Herein, we first report, a simple electrochemical immunosensor based on methylene blue dye (MB) immobilized graphene oxide modified glassy carbon electrode (GCE/GO@MB) for selective, quick (35 ± 5 mins) and raw sample analysis of WSSV. The immunosensor was prepared by sequential modification of primary antibody, blocking agent (bovine serum album), antigen (as vp28 protein), secondary antibody coupled with horseradish peroxidase (Ab2-HRP) on the GCE/GO@MB. The modified electrode showed a well-defined redox peak at an equilibrium potential (E1/2), -0.4 V vs Ag/AgCl and mediated H2O2 reduction reaction without any false positive result and dissolved oxygen interferences in pH 7 phosphate buffer solution. Under an optimal condition, constructed calibration plot was linear in a range of 1.36 × 10-3 to 1.36 × 107 copies μL-1 of vp28. It is about four orders higher sensitive than that of the values observed with polymerase chain reaction (PCR) and western blot based WSSV detection techniques. Direct electrochemical immunosensing of WSSV in raw tissue samples were successfully demonstrated as a real sample system.

  9. Turner Syndrome: Neuroimaging Findings--Structural and Functional

    Science.gov (United States)

    Mullaney, Ronan; Murphy, Declan

    2009-01-01

    Neuroimaging studies of Turner syndrome can advance our understanding of the X chromosome in brain development, and the modulatory influence of endocrine factors. There is increasing evidence from neuroimaging studies that TX individuals have significant differences in the anatomy, function, and metabolism of a number of brain regions; including…

  10. Applications of Bayesian Phylodynamic Methods in a Recent U.S. Porcine Reproductive and Respiratory Syndrome Virus Outbreak

    Directory of Open Access Journals (Sweden)

    Mohammad A. Alkhamis

    2016-02-01

    Full Text Available Classical phylogenetic methods such as neighbor-joining or maximum likelihood trees, provide limited inferences about the evolution of important pathogens and ignore important evolutionary parameters and uncertainties, which in turn limits decision making related to surveillance, control and prevention resources. Bayesian phylodynamic models have recently been used to test research hypothesis related to evolution of infectious agents. However, few studies have attempted to model the evolutionary dynamics of porcine reproductive and respiratory syndrome virus (PRRSV and, to the authors’ knowledge, no attempt has been made to use large volumes of routinely collected data, sometimes referred to as big data, in the context of animal disease surveillance. The objective of this study was to explore and discuss the applications of Bayesian phylodynamic methods for modeling the evolution and spread of a notable 1-7-4 RFLP-type PRRSV between 2014 and 2015. A convenience sample of 288 ORF5 sequences was collected from 5 swine production systems in the United States between September 2003 and March 2015. Using coalescence and discrete trait phylodynamic models, we were able to infer population growth and demographic history of the virus, identified the most likely ancestral system (root state posterior probability = 0.95 and revealed significant dispersal routes (Bayes factor > 6 of viral exchange among systems. Results indicate that currently circulating viruses are evolving rapidly, and show a higher level of relative genetic diversity over time, when compared to earlier relatives. Biological soundness of model results is supported by the finding that sow farms were responsible for PRRSV spread within the systems. Such results can’t be obtained by traditional phylogenetic methods, and therefore, our results provide a methodological framework for molecular epidemiological modeling of new PRRSV outbreaks and demonstrate the prospects of phylodynamic

  11. Studies of the viral binding proteins of shrimp BP53, a receptor of white spot syndrome virus.

    Science.gov (United States)

    Li, Chen; Gao, Xiao-Xiao; Huang, Jie; Liang, Yan

    2016-02-01

    The specific binding between viral attachment proteins (VAPs) of a virus and its cellular receptors on host cells mediates virus entry into host cells, which triggers subsequent viral infections. Previous studies indicate that F1 ATP synthase β subunit (named BP53), is found on the surface of shrimp cells and involved in white spot syndrome virus (WSSV) infection by functioning as a potential viral receptor. Herein, in a far-western blotting assay, three WSSV proteins with molecular weights of 28 kDa, 37 kDa, and >50 kDa were found to interact with BP53. The 28 kDa and 37 kDa proteins were identified as the envelope protein VP28 and VP37 of WSSV respectively, which could be recognized by the polyclonal antibodies. Enzyme-linked immunosorbent binding assays revealed that VP37 contributed to almost 80% of the binding capability for BP53 compared with the same amount of total WSSV protein. The relationship between BP53 and its complementary interacting protein, VP37, was visualized using a co-localization assay. Bound VP37 on the cell surface co-localized with BP53 and shared a similar subcellular location on the outer surface of shrimp cells. Pearson's correlation coefficients reached to 0.67 ± 0.05 and the Mander's overlap coefficients reached 0.70 ± 0.05, which indicated a strong relationship between the localization of BP53 and bound rVP37. This provides evidence for an interaction between BP53 and VP37 obtained at the molecular and cellular levels, supporting the hypothesis that BP53 serves as a receptor for WSSV by binding to VP37. The identification of the viral binding proteins of shrimp BP53 is helpful for better understanding the pathogenic mechanisms of WSSV to infect shrimp at the cellular level. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. A Novel Vascular Endothelial Growth Factor Receptor Participates in White Spot Syndrome Virus Infection in Litopenaeus vannamei

    Directory of Open Access Journals (Sweden)

    Shihao Li

    2017-11-01

    Full Text Available Vascular endothelial growth factor (VEGF signaling pathway is known to play key roles in endothelial cell proliferation, migration, angiogenesis, vascular permeability, inhibition of apoptosis, and virus infection. In the present study, a novel VEGFR gene (LvVEGFR2 was identified and characterized from Litopenaeus vannamei. The deduced amino acid sequence of LvVEGFR2 possessed typical features of VEGFRs reported in other species, including six IG-like domains, a transmembrane motif, a protein kinase (PK domain, and one tyrosine-PK active site. The transcripts of LvVEGFR2 were mainly detected in hemocytes and lymphoid organ (Oka. Subcellular localization analysis showed that LvVEGFR2 was a membrane protein. Its expression level was obviously upregulated in hemocytes and Oka of the shrimp after white spot syndrome virus (WSSV infection. Knockdown of LvVEGFR2 gene expression by double-strand RNA mediated interference could lead to a decrease of virus copy number in WSSV-infected shrimp. The interaction between LvVEGFR2 and different LvVEGFs (LvVEGF1, LvVEGF2, and LvVEGF3 in shrimp was analyzed at the transcription level and protein level, respectively. Knockdown of LvVEGF2 or LvVEGF3 could downregulate the expression level of LvVEGFR2, and injection of the recombinant LvVEGF2 or LvVEGF3 could upregulate the expression level of LvVEGFR2. Yeast two-hybrid analysis showed that LvVEGFR2 could interact with LvVEGF2 and LvVEGF3 directly. The study improved our understanding on the VEGF signaling pathway of shrimp and its role during WSSV infection.

  13. Induction of T helper 3 regulatory cells by dendritic cells infected with porcine reproductive and respiratory syndrome virus

    International Nuclear Information System (INIS)

    Silva-Campa, Erika; Flores-Mendoza, Lilian; Resendiz, Monica; Pinelli-Saavedra, Araceli; Mata-Haro, Veronica; Mwangi, Waithaka; Hernandez, Jesus

    2009-01-01

    Delayed development of virus-specific immune response has been observed in pigs infected with the porcine reproductive and respiratory syndrome virus (PRRSV). Several studies support the hypothesis that the PRRSV is capable of modulating porcine immune system, but the mechanisms involved are yet to be defined. In this study, we evaluated the induction of T regulatory cells by PRRSV-infected dendritic cells (DCs). Our results showed that PRRSV-infected DCs significantly increased Foxp3 + CD25 + T cells, an effect that was reversible by IFN-α treatment, and this outcome was reproducible using two distinct PRRSV strains. Analysis of the expressed cytokines suggested that the induction of Foxp3 + CD25 + T cells is dependent on TGF-β but not IL-10. In addition, a significant up-regulation of Foxp3 mRNA, but not TBX21 or GATA3, was detected. Importantly, our results showed that the induced Foxp3 + CD25 + T cells were able to suppress the proliferation of PHA-stimulated PBMCs. The T cells induced by the PRRSV-infected DCs fit the Foxp3 + CD25 + T helper 3 (Th3) regulatory cell phenotype described in the literature. The induction of this cell phenotype depended, at least in part, on PRRSV viability because IFN-α treatment or virus inactivation reversed these effects. In conclusion, this data supports the hypothesis that the PRRSV succeeds to establish and replicate in porcine cells early post-infection, in part, by inducing Th3 regulatory cells as a mechanism of modulating the porcine immune system.

  14. Structure of Epstein-Barr Virus Glycoprotein 42 Suggests a Mechanism for Triggering Receptor-Activated Virus Entry

    Energy Technology Data Exchange (ETDEWEB)

    Kirschner, Austin N.; Sorem, Jessica; Longnecker, Richard; Jardetzky, Theodore S.; (NWU); (Stanford-MED)

    2009-05-26

    Epstein-Barr virus requires glycoproteins gH/gL, gB, and gp42 to fuse its lipid envelope with B cells. Gp42 is a type II membrane protein consisting of a flexible N-terminal region, which binds gH/gL, and a C-terminal lectin-like domain that binds to the B-cell entry receptor human leukocyte antigen (HLA) class II. Gp42 triggers membrane fusion after HLA binding, a process that requires simultaneous binding to gH/gL and a functional hydrophobic pocket in the lectin domain adjacent to the HLA binding site. Here we present the structure of gp42 in its unbound form. Comparisons to the previously determined structure of a gp42:HLA complex reveals additional N-terminal residues forming part of the gH/gL binding site and structural changes in the receptor binding domain. Although the core of the lectin domain remains similar, significant shifts in two loops and an {alpha} helix bordering the essential hydrophobic pocket suggest a structural mechanism for triggering fusion.

  15. Isolation and Identification of Egg Drop Syndrome Virus with Hemagglutination and Hemagglutination Tests

    Directory of Open Access Journals (Sweden)

    Fidyah Fitrawati

    2015-11-01

    of 0,8. The HA test in uterine sample of both SR/WNO/2011 and FF/Sleman/2011 showed the titer 23 HA units and egg washed water sample of FF/Sleman/2011 showed titer 22 HA units. The HI test for comparison with ND and AI anti serum was negative, while the test with EDS anti serum showed positive results. Based on the HA and HI test results, it was concluded that the virus grown in the allantoic fluid is EDS virus.

  16. CLUSTER MODEL FOR EXTENSIVE GIANT TIGER SHRIMP (Penaeus monodon Fab. TO PREVENT TRANSMISSION OF WHITE SPOT SYNDROME VIRUS

    Directory of Open Access Journals (Sweden)

    Arief Taslihan

    2015-06-01

    Full Text Available White spot syndrome virus (WSSV has become epidemic in Indonesia and affecting shrimp aquaculture interm of its production. White spot syndrome virus is transmitted from one to other ponds, through crustacean, included planktonic copepode as carrier for WSSV and through water from affected shrimp pond. A cluster model, consist of shrimp grow out ponds surrounded by non-shrimp pond as a role of biosecurity has been developed. The model aimed to prevent white spot virus transmission in extensive giant tiger shrimp pond. The study was conducted in two sites at Demak District, Central Java Province. As the treatment, a cluster consist of three shrimp ponds in site I, and two shrimp ponds in site II, each was surrounded by buffer ponds rearing only finfish. As the control, five extensive shrimp grow out ponds in site I and three shrimp grow out ponds in site II, with shrimp pond has neither applied biosecurity nor surrounded by non-shrimp pond as biosecurity as well considered as control ponds. The results found that treatment of cluster shrimp ponds surrounded by non-shrimp ponds could hold shrimp at duration of culture in the grow out pond (DOC 105.6±4.5 days significantly much longer than that of control that harvested at 60.9±16.0 days due to WSSV outbreak. Survival rate in trial ponds was 77.6±3.6%, significantly higher than that of control at 22.6±15.8%. Shrimp production in treatment ponds has total production of 425.1±146.6 kg/ha significantly higher than that of control that could only produced 54.5±47.6 kg/ha. Implementation of Better Management Practices (BMP by arranging shrimp ponds in cluster and surrounding by non-shrimp ponds proven effectively prevent WSSV transmission from traditional shrimp ponds in surrounding area.

  17. Structural basis of Zika virus methyltransferase inhibition by sinefungin

    Czech Academy of Sciences Publication Activity Database

    Hercík, Kamil; Brynda, Jiří; Nencka, Radim; Bouřa, Evžen

    2017-01-01

    Roč. 162, č. 7 (2017), s. 2091-2096 ISSN 0304-8608 R&D Projects: GA MŠk LO1302 Institutional support: RVO:61388963 Keywords : crystal structure * flavivirus RNA * NS5 Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 2.058, year: 2016

  18. Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol

    Energy Technology Data Exchange (ETDEWEB)

    Kadam, Rameshwar U.; Wilson, Ian A.

    2016-12-21

    The broad-spectrum antiviral drug Arbidol shows efficacy against influenza viruses by targeting the hemagglutinin (HA) fusion machinery. However, the structural basis of the mechanism underlying fusion inhibition by Arbidol has remained obscure, thereby hindering its further development as a specific and optimized influenza therapeutic. We determined crystal structures of Arbidol in complex with influenza virus HA from pandemic 1968 H3N2 and recent 2013 H7N9 viruses. Arbidol binds in a hydrophobic cavity in the HA trimer stem at the interface between two protomers. This cavity is distal to the conserved epitope targeted by broadly neutralizing stem antibodies and is ~16 Å from the fusion peptide. Arbidol primarily makes hydrophobic interactions with the binding site but also induces some conformational rearrangements to form a network of inter- and intraprotomer salt bridges. By functioning as molecular glue, Arbidol stabilizes the prefusion conformation of HA that inhibits the large conformational rearrangements associated with membrane fusion in the low pH of the endosome. This unique binding mode compared with the small-molecule inhibitors of other class I fusion proteins enhances our understanding of how small molecules can function as fusion inhibitors and guides the development of broad-spectrum therapeutics against influenza virus.

  19. Structure of Cowpea mottle virus: a consensus in the genus Carmovirus

    International Nuclear Information System (INIS)

    Ke Jiyuan; Schmidt, Timothy; Chase, Elaine; Bozarth, Robert F.; Smith, Thomas J.

    2004-01-01

    Cowpea mottle virus (CPMoV) is a T = 3 virus that belongs to Carmovirus genus of the Tombusviridae family. Here, we report the crystal structure of CPMoV determined to a resolution of 7.0 A. The structures and sequences of three Carmoviruses, CPMoV, Turnip crinkle virus (TCV), and Carnation mottle virus (CarMV) have been compared to TBSV from the Tombusvirus genus. CPMoV, TCV, and CarMV all have a deletion in βC strand in the S domain relative to TBSV that may be distinctive to the genus. Although CPMoV has an elongated C-terminus like TBSV, it does not interact with the icosahedrally related P domain as observed in TBSV. In CPMoV, the termini of A and B interact with the icosahedrally related shell domains of A and C, respectively, to form a chain of interactions around the 5-fold axes. The C subunit terminus does not, however, interact with the B subunit because of quasi-equivalent differences in the P domain orientations

  20. 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.

  1. The 3.2 Angstrom Resolution Structure of the Polymorphic Cowpea Chlorotic Mottle Virus Ribonucleoprotein Particle

    Science.gov (United States)

    Speir, Jeffrey Alan

    Structural studies of the polymorphic cowpea chlorotic mottle virus have resulted in high resolution structures for two distinct icosahedral ribonucleoprotein particle conformations dependent upon whether acidic or basic pH conditions prevail. CCMV is stable below pH 6.5, however metal-free particles maintain a 10% increase in hydrodynamic volume at pH >=q 7.5. Identification of this swollen' form of CCMV, which can easily be disrupted with 1M NaCl, led to the first reassembly of an icosahedral virus in vitro from purified viral protein and RNA to form infectious particles, and its assembly has been the subject of biochemical and biophysical investigations for over twenty-five years. Under well defined conditions of pH, ionic strength and divalent metal ion concentration, CCMV capsid protein or capsid protein and RNA will reassemble to form icosahedral particles of various sizes, sheets, tubes, rosettes, and a variety of laminar structures which resemble virion structures from non-related virus families. Analysis of native particles at 3.2A resolution and swollen particles at 28A resolution has suggested that the chemical basis for the formation of polymorphic icosahedral and anisometric structures is: (i) hexamers formed of beta-barrel subunits stabilized by an unusual hexameric parallel beta structure made up of their N-termini, (ii) the location of protein-RNA interactions, (iii) divalent metal cation binding sites that regulate quasi-symmetrical subunit associations, (iv) charge repulsion across the same interfaces when lacking divalent metal ions at basic pH, which induces the formation of sixty 20A diameter portals for RNA release, and (v) a novel, C-terminal-based, subunit dimer assembly unit. The use of C- and N-terminal arms in CCMV has not been observed in other icosahedral RNA virus structures determined at near atomic resolution, however, their detailed interactions and roles in stabilizing the quaternary organization of CCMV are related to that found

  2. Structural study of gubernaculum testis in fetuses with prune belly syndrome.

    Science.gov (United States)

    Costa, Suelen F; Costa, Waldemar S; Sampaio, Francisco J B; Favorito, Luciano A

    2015-05-01

    We compared and contrasted the structure of the gubernaculum testis in fetuses with prune belly syndrome and normal controls. We studied a total of 6 gubernacula from 3 male fetuses with prune belly syndrome and a total of 14 from 7 male fetuses without an anomaly. Gubernacular specimens were cut into 5 μm sections and stained with Masson trichrome to quantify connective tissue and smooth muscle cells, with Weigert stain to observe elastic fibers and with picrosirius red with polarization to observe collagen. Immunohistochemical analysis was done with tubulin to observe the nerves. Images were captured with a BX51 microscope and DP70 camera (Olympus®). Stereological analysis was done with Image-Pro and ImageJ (MediaCybernetics®) using a grid to determine volumetric density. Means were statistically compared with the Mann-Whitney test. All tests were 2-sided with p Prune belly syndrome fetuses were at 17 to 31 weeks of gestation and control fetuses were at 12 to 35 weeks of gestation. Quantitative analysis showed no difference in the volumetric density of smooth muscle cells in prune belly syndrome vs control gubernacula (mean 15.70% vs 19%, p = 0.2321). Collagen fiber analysis revealed a predominance of green areas in prune belly syndrome gubernacula, suggesting collagen type III, and a predominance of red areas in control gubernacula, suggesting collagen type I. Elastic fibers were significantly smaller in prune belly syndrome gubernacula than in control gubernacula (mean 14.06% vs 24.6%, p = 0.0190). Quantitative analysis demonstrated no difference in the volumetric density of nerves in prune belly syndrome or control gubernacula (mean 5.200% vs 3.158%, p = 0.2302). The gubernaculum in fetuses with prune belly syndrome had altered concentrations of collagen and elastic fibers. These structural alterations could be one of the factors involved in cryptorchidism in prune belly syndrome. Copyright © 2015. Published by Elsevier Inc.

  3. [Hantavirus pulmonary syndrome (Rio Mamore virus) in the Peruvian Amazon region].

    Science.gov (United States)

    Casapía, Martín; Mamani, Enrique; García, María P; Miraval, María L; Valencia, Pedro; Quino, Alberto H; Alvarez, Carlos; Donaires, Luis F

    2012-01-01

    Hantavirus infection is a viral zoonotic infection borne by rodents which most letal form clinical is the Hantavirus Pulmonary Syndrome (SPH, Spanish abbreviation). The Mamore River variant originates in South America and was found in rodents without any association to human diseases. Two cases of SPH were identified in the Peruvian Amazon region in November 2011. In both cases, a molecular diagnostic testing was conducted by the Instituto Nacional de Salud from Peru. A phylogenetic analysis of a viral genome fragment and a histopathological evaluation were conducted. Both patients developed adult respiratory distress syndrome and refractory shock. A patient died and another one recovered 12 days later.

  4. Identification of a major non-structural protein in the nuclei of Rift Valley fever virus-infected cells.

    Science.gov (United States)

    Struthers, J K; Swanepoel, R

    1982-06-01

    A non-structural protein of mol. wt. 34 X 10(3) was demonstrated in the nuclei of Rift Valley fever virus-infected Vero cells by SDS-polyacrylamide gel electro-phoresis. The protein appears to correspond to the virus-induced antigen demonstrated by indirect immunofluorescence in intranuclear inclusions.

  5. Comparison of Newly Assembled Full Length HIV-1 Integrase With Prototype Foamy Virus Integrase: Structure-Function Prospective.

    Science.gov (United States)

    Dayer, Mohammad Reza

    2016-05-01

    Drug design against human immunodeficiency virus type 1 (HIV-1) integrase through its mechanistic study is of great interest in the area in biological research. The main obstacle in this area is the absence of the full-length crystal structure for HIV-1 integrase to be used as a model. A complete structure, similar to HIV-1 of a prototype foamy virus integrase in complex with DNA, including all conservative residues, is available and has been extensively used in recent investigations. The aim of this study was to determine whether the above model is precisely representative of HIV-1 integrase. This would critically determine the success of any designed drug using the model in deactivation of integrase and AIDS treatment. Primarily, a new structure for HIV-1 was constructed, using a crystal structure of prototype foamy virus as the starting structure. The constructed structure of HIV-1 integrase was simultaneously simulated with a prototype foamy virus integrase on a separate occasion. Our results indicate that the HIV-1 system behaves differently from the prototype foamy virus in terms of folding, hydration, hydrophobicity of binding site and stability. Based on our findings, we can conclude that HIV-1 integrase is vastly different from the prototype foamy virus integrase and does not resemble it, and the modeling output of the prototype foamy virus simulations could not be simply generalized to HIV-1 integrase. Therefore, our HIV-1 model seems to be more representative and more useful for future research.

  6. Crystallization and preliminary X-ray structural studies of adeno-associated virus serotype 6

    International Nuclear Information System (INIS)

    Xie, Qing; Ongley, Heather M.; Hare, Joan; Chapman, Michael S.

    2008-01-01

    Adeno-associated virus type 6, a human DNA virus that is being developed as a vector for gene therapy, has been crystallized in a form suitable for structure determination at about 3.2 Å resolution. Adeno-associated viruses are being developed as vectors for gene therapy and have been used in a number of clinical trials. Vectors to date have been based on the type species AAV-2, the structure of which was published in 2002. There is growing interest in modulating the cellular tropism and immune neutralization of AAV-2 with variants inspired by the properties of other serotypes. Towards the determination of a structure for AAV type 6, this paper reports the high-yield production, purification, crystallization and preliminary diffraction studies of infectious AAV-6 virions. The crystals diffracted to 3.2 Å resolution using synchrotron radiation. The most promising crystal form belonged to space group R3 and appeared to be suitable for initial structure determination

  7. Crystal Structure of the Oligomeric Form of Lassa Virus Matrix Protein Z.

    Science.gov (United States)

    Hastie, Kathryn M; Zandonatti, Michelle; Liu, Tong; Li, Sheng; Woods, Virgil L; Saphire, Erica Ollmann

    2016-05-01

    The arenavirus matrix protein Z is highly multifunctional and occurs in both monomeric and oligomeric forms. The crystal structure of a dodecamer of Z from Lassa virus, presented here, illustrates a ring-like structure with a highly basic center. Mutagenesis demonstrates that the dimeric interface within the dodecamer and a Lys-Trp-Lys triad at the center of the ring are important for oligomerization. This structure provides an additional template to explore the many functions of Z. The arenavirus Lassa virus causes hundreds of thousands of infections each year, many of which develop into fatal hemorrhagic fever. The arenavirus matrix protein Z is multifunctional, with at least four distinct roles. Z exists in both monomeric and oligomeric forms, each of which likely serves a specific function in the viral life cycle. Here we present the dodecameric form of Lassa virus Z and demonstrate that Z forms a "wreath" with a highly basic center. This structure and that of monomeric Z now provide a pair of critical templates by which the multiple roles of Z in the viral life cycle may be interpreted. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. Nuclear imprisonment of host cellular mRNA by nsp1β protein of porcine reproductive and respiratory syndrome virus

    International Nuclear Information System (INIS)

    Han, Mingyuan; Ke, Hanzhong; Zhang, Qingzhan; Yoo, Dongwan

    2017-01-01

    Positive-strand RNA genomes function as mRNA for viral protein synthesis which is fully reliant on host cell translation machinery. Competing with cellular protein translation apparatus needs to ensure the production of viral proteins, but this also stifles host innate defense. In the present study, we showed that porcine reproductive and respiratory syndrome virus (PRRSV), whose replication takes place in the cytoplasm, imprisoned host cell mRNA in the nucleus, which suggests a novel mechanism to enhance translation of PRRSV genome. PRRSV nonstructural protein (nsp) 1β was identified as the nuclear protein playing the role for host mRNA nuclear retention and subversion of host protein synthesis. A SAP (SAF-A/B, Acinus, and PIAS) motif was identified in nsp1β with the consensus sequence of 126 -LQxxLxxxGL- 135 . In situ hybridization unveiled that SAP mutants were unable to cause nuclear retention of host cell mRNAs and did not suppress host protein synthesis. In addition, these SAP mutants reverted PRRSV-nsp1β-mediated suppression of interferon (IFN) production, IFN signaling, and TNF-α production pathway. Using reverse genetics, a series of SAP mutant PRRS viruses, vK124A, vL126A, vG134A, and vL135A were generated. No mRNA nuclear retention was observed during vL126A and vL135A infections. Importantly, vL126A and vL135A did not suppress IFN production. For other arteriviruses, mRNA nuclear accumulation was also observed for LDV-nsp1β and SHFV-nsp1β. EAV-nsp1 was exceptional and did not block the host mRNA nuclear export. - Highlights: •PRRS virus blocks host mRNA nuclear export to the cytoplasm. •PRRSV nsp1β is the viral protein responsible for host mRNA nuclear retention. •SAP domain in nsp1β is essential for host mRNA nuclear retention and type I interferon suppression. •Mutation in the SAP domain of nsp1β causes the loss of function. •Host mRNA nuclear retention by nsp1β is common in the family Arteriviridae, except equine arteritis virus.

  9. Nuclear imprisonment of host cellular mRNA by nsp1β protein of porcine reproductive and respiratory syndrome virus

    Energy Technology Data Exchange (ETDEWEB)

    Han, Mingyuan, E-mail: hanming@umich.edu; Ke, Hanzhong; Zhang, Qingzhan; Yoo, Dongwan, E-mail: dyoo@illinois.edu

    2017-05-15

    Positive-strand RNA genomes function as mRNA for viral protein synthesis which is fully reliant on host cell translation machinery. Competing with cellular protein translation apparatus needs to ensure the production of viral proteins, but this also stifles host innate defense. In the present study, we showed that porcine reproductive and respiratory syndrome virus (PRRSV), whose replication takes place in the cytoplasm, imprisoned host cell mRNA in the nucleus, which suggests a novel mechanism to enhance translation of PRRSV genome. PRRSV nonstructural protein (nsp) 1β was identified as the nuclear protein playing the role for host mRNA nuclear retention and subversion of host protein synthesis. A SAP (SAF-A/B, Acinus, and PIAS) motif was identified in nsp1β with the consensus sequence of {sub 126}-LQxxLxxxGL-{sub 135}. In situ hybridization unveiled that SAP mutants were unable to cause nuclear retention of host cell mRNAs and did not suppress host protein synthesis. In addition, these SAP mutants reverted PRRSV-nsp1β-mediated suppression of interferon (IFN) production, IFN signaling, and TNF-α production pathway. Using reverse genetics, a series of SAP mutant PRRS viruses, vK124A, vL126A, vG134A, and vL135A were generated. No mRNA nuclear retention was observed during vL126A and vL135A infections. Importantly, vL126A and vL135A did not suppress IFN production. For other arteriviruses, mRNA nuclear accumulation was also observed for LDV-nsp1β and SHFV-nsp1β. EAV-nsp1 was exceptional and did not block the host mRNA nuclear export. - Highlights: •PRRS virus blocks host mRNA nuclear export to the cytoplasm. •PRRSV nsp1β is the viral protein responsible for host mRNA nuclear retention. •SAP domain in nsp1β is essential for host mRNA nuclear retention and type I interferon suppression. •Mutation in the SAP domain of nsp1β causes the loss of function. •Host mRNA nuclear retention by nsp1β is common in the family Arteriviridae, except equine

  10. Chromatin Structure of Epstein-Barr Virus Latent Episomes.

    Science.gov (United States)

    Lieberman, Paul M

    2015-01-01

    EBV latent infection is characterized by a highly restricted pattern of viral gene expression. EBV can establish latent infections in multiple different tissue types with remarkable variation and plasticity in viral transcription and replication. During latency, the viral genome persists as a multi-copy episome, a non-integrated-closed circular DNA with nucleosome structure similar to cellular chromosomes. Chromatin assembly and histone modifications contribute to the regulation of viral gene expression, DNA replication, and episome persistence during latency. This review focuses on how EBV latency is regulated by chromatin and its associated processes.

  11. Structural Insights into Immune Recognition of the Severe Acute Respiratory Syndrome Coronavirus S Protein Receptor Binding Domain

    Energy Technology Data Exchange (ETDEWEB)

    Pak, J.; Sharon, C; Satkunarajah, M; Thierry, C; Cameron, C; Kelvin, D; Seetharaman, J; Cochrane, A; Plummer, F; et. al.

    2009-01-01

    The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) is responsible for host cell attachment and fusion of the viral and host cell membranes. Within S the receptor binding domain (RBD) mediates the interaction with angiotensin-converting enzyme 2 (ACE2), the SARS-CoV host cell receptor. Both S and the RBD are highly immunogenic and both have been found to elicit neutralizing antibodies. Reported here is the X-ray crystal structure of the RBD in complex with the Fab of a neutralizing mouse monoclonal antibody, F26G19, elicited by immunization with chemically inactivated SARS-CoV. The RBD-F26G19 Fab complex represents the first example of the structural characterization of an antibody elicited by an immune response to SARS-CoV or any fragment of it. The structure reveals that the RBD surface recognized by F26G19 overlaps significantly with the surface recognized by ACE2 and, as such, suggests that F26G19 likely neutralizes SARS-CoV by blocking the virus-host cell interaction.

  12. The correlation between perceived social support and illness uncertainty in people with human immunodeficiency virus/acquired immune deficiency syndrome in Iran

    Directory of Open Access Journals (Sweden)

    Moosa Sajjadi

    2015-01-01

    Full Text Available Background: Illness uncertainty is a source of a chronic and pervasive psychological stress for people living with human immunodeficiency virus (HIV/acquired immune deficiency syndrome (AIDS (PLWH, and largely affects their quality of life and the ability to cope with the disease. Based on the uncertainty in illness theory, the social support is one of the illness uncertainty antecedents, and influences the level of uncertainty perceived by patients. Aim: To examine uncertainty in PLWH and its correlation with social support in Iran. Materials and Methods: This cross-sectional correlational study was conducted with 80 PLWH presenting to AIDS Research Center, Tehran, Iran in 2013. The data collected using illness uncertainty and social support inventories were analyzed through Pearson′s correlation coefficient, Spearman′s correlation coefficient, and regression analysis. Results: The results showed a high level of illness uncertainty in PLWH and a negative significant correlation between perceived social support and illness uncertainty ( P = 0.01, r = -0.29. Conclusion: Uncertainty is a serious aspect of illness experience in Iranian PLWH. Providing adequate, structured information to patients as well as opportunities to discuss their concerns with other PLWH and receive emotional support from their health care providers may be worthwhile.

  13. Genomic variation in macrophage-cultured European porcine reproductive and respiratory syndrome virus Olot/91 revealed using ultra-deep next generation sequencing.

    Science.gov (United States)

    Lu, Zen H; Brown, Alexander; Wilson, Alison D; Calvert, Jay G; Balasch, Monica; Fuentes-Utrilla, Pablo; Loecherbach, Julia; Turner, Frances; Talbot, Richard; Archibald, Alan L; Ait-Ali, Tahar

    2014-03-04

    Porcine Reproductive and Respiratory Syndrome (PRRS) is a disease of major economic impact worldwide. The etiologic agent of this disease is the PRRS virus (PRRSV). Increasing evidence suggest that microevolution within a coexisting quasispecies population can give rise to high sequence heterogeneity in PRRSV. We developed a pipeline based on the ultra-deep next generation sequencing approach to first construct the complete genome of a European PRRSV, strain Olot/9, cultured on macrophages and then capture the rare variants representative of the mixed quasispecies population. Olot/91 differs from the reference Lelystad strain by about 5% and a total of 88 variants, with frequencies as low as 1%, were detected in the mixed population. These variants included 16 non-synonymous variants concentrated in the genes encoding structural and nonstructural proteins; including Glycoprotein 2a and 5. Using an ultra-deep sequencing methodology, the complete genome of Olot/91 was constructed without any prior knowledge of the sequence. Rare variants that constitute minor fractions of the heterogeneous PRRSV population could successfully be detected to allow further exploration of microevolutionary events.

  14. Non-Canonical Roles of Dengue Virus Non-Structural Proteins

    Directory of Open Access Journals (Sweden)

    Julianna D. Zeidler

    2017-03-01

    Full Text Available The Flaviviridae family comprises a number of human pathogens, which, although sharing structural and functional features, cause diseases with very different outcomes. This can be explained by the plurality of functions exerted by the few proteins coded by viral genomes, with some of these functions shared among members of a same family, but others being unique for each virus species. These non-canonical functions probably have evolved independently and may serve as the base to the development of specific therapies for each of those diseases. Here it is discussed what is currently known about the non-canonical roles of dengue virus (DENV non-structural proteins (NSPs, which may account for some of the effects specifically observed in DENV infection, but not in other members of the Flaviviridae family. This review explores how DENV NSPs contributes to the physiopathology of dengue, evasion from host immunity, metabolic changes, and redistribution of cellular components during infection.

  15. Selective constraints, molecular recombination structure and phylogenetic reconstruction of isometric plant RNA viruses of the families Luteoviridae and Tymoviridae.

    Science.gov (United States)

    Boulila, Moncef

    2011-02-01

    In an effort to enhance the knowledge on molecular evolution of currently the known members of the families Luteoviridae and Tymoviridae, in-depth molecular investigations in the entire genome of 147 accessions retrieved from the international databases, were carried out. Two algorithms (RECCO and RDP version 3.31β) adapted to the mosaic structure of viruses were utilized. The recombination frequency along the sequences was dissected and demonstrated that the three virus genera of the family Luteoviridae comprise numerous members subjected to recombination. It has pointed out that the major viruses swapped a few but long genomic segments. In addition, in Barley yellow dwarf virus, heredity material might be exchanged between two different serotypes. Even more, putative recombination events occurred between two different genera. Based on Fisher's Exact Test of Neutrality, positive selection acting on protein expression was detected only in the poleroviruses Cereal yellow dwarf virus, Potato leafroll virus and Wheat yellow dwarf virus. In contrast, several components of the family Tymoviridae were highly recombinant. Genomic portion exchange arose in many positions consisting of short fragments. Furthermore, no positive selection was detected. The evolutionary history showed, in the Luteoviridae, that all screened isolates split into three clusters corresponding to the three virus genera forming this family. Moreover, in the serotype PAV of Barley yellow dwarf virus, two major clades corresponding to PAV-USA and PAV-China, were delineated. Similarly, in the Tymoviridae, all analyzed isolates fell into four groups corresponding to the three virus genera composing this family along with the unclassified Tymoviridae. Inferred phylogenies reshuffled the existing classification and showed that Wheat yellow dwarf virus-RPV was genetically closely related to Cereal yellow dwarf virus and the unclassified Tymoviridae Grapevine syrah virus-1 constituted an integral part of

  16. Antigenic characterization of small, round-structured viruses by immune electron microscopy.

    OpenAIRE

    Okada, S; Sekine, S; Ando, T; Hayashi, Y; Murao, M; Yabuuchi, K; Miki, T; Ohashi, M

    1990-01-01

    Small, round-structured viruses (SRSVs) detected from nonbacterial gastroenteritis outbreaks in Tokyo and Saitama Prefecture, Japan, during the period from 1977 to 1988 were tentatively classified into nine antigenic patterns from SRSV-1 (S-1) to SRSV-9 (S-9) by cross-immune electron microscopy (IEM). S-1 and S-2 appeared pattern specific, while S-3 to S-9, distinguishable from each other in their reactivity, appeared somewhat antigenically related. Their antigenic relatedness to the Norwal, ...

  17. Mannosyl Glycodendritic Structure Inhibits DC-SIGN-Mediated Ebola Virus Infection in cis and in trans

    OpenAIRE

    Lasala, Fátima; Arce, Eva; Otero, Joaquín R.; Rojo, Javier; Delgado, Rafael

    2003-01-01

    We have designed a glycodendritic structure, BH30sucMan, that blocks the interaction between dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and Ebola virus (EBOV) envelope. BH30sucMan inhibits DC-SIGN-mediated EBOV infection at nanomolar concentrations. BH30sucMan may counteract important steps of the infective process of EBOV and, potentially, of microorganisms shown to exploit DC-SIGN for cell entry and infection.

  18. Mannosyl Glycodendritic Structure Inhibits DC-SIGN-Mediated Ebola Virus Infection in cis and in trans

    Science.gov (United States)

    Lasala, Fátima; Arce, Eva; Otero, Joaquín R.; Rojo, Javier; Delgado, Rafael

    2003-01-01

    We have designed a glycodendritic structure, BH30sucMan, that blocks the interaction between dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and Ebola virus (EBOV) envelope. BH30sucMan inhibits DC-SIGN-mediated EBOV infection at nanomolar concentrations. BH30sucMan may counteract important steps of the infective process of EBOV and, potentially, of microorganisms shown to exploit DC-SIGN for cell entry and infection. PMID:14638512

  19. Expression of Recombinant Potato leafroll virus Structural and Non-structural Proteins for Antibody Production

    Czech Academy of Sciences Publication Activity Database

    Plchová, Helena; Moravec, Tomáš; Dědič, P.; Čeřovská, Noemi

    2011-01-01

    Roč. 159, č. 2 (2011), s. 130-132 ISSN 0931-1785 R&D Projects: GA MŠk 1M06030; GA MZe QH71123 Institutional research plan: CEZ:AV0Z50380511 Keywords : Potato leafroll virus * recombinant viral antigen * antibody production Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.791, year: 2011

  20. Relationship between white spot syndrome virus (WSSV) loads and characterizations of water quality in Litopenaeus vannamei culture ponds during the tropical storm.

    Science.gov (United States)

    Zhang, J S; Li, Z J; Wen, G L; Wang, Y L; Luo, L; Zhang, H J; Dong, H B

    2016-01-01

    An in-situ experiment was conducted to investigate the effect of tropical storm on the white spot syndrome virus (WSSV) loads in Litopenaeus vannamei rearing ponds. White spot syndrome virus loads, heterotrophic bacteria, Vibrio and water quality (including temperature, dissolved oxygen (DO), salinity, pH, NH 4 -N, and NO 2 -N) were continually monitored through one tropical storm. The WSSV loads decreased when tropical storm made landfall, and substantially increased when typhoon passed. The variation of WSSV loads was correlated with DO, temperature, heterotrophic bacteria count, and ammonia-N concentrations. These results suggested that maintaining high level DO and promoting heterotrophic bacteria growth in the shrimp ponds might prevent the diseases' outbreak after the landfall of tropical storm.

  1. Dengue death with evidence of hemophagocytic syndrome and dengue virus infection in the bone marrow.

    Science.gov (United States)

    Ab-Rahman, Hasliana Azrah; Wong, Pooi-Fong; Rahim, Hafiz; Abd-Jamil, Juraina; Tan, Kim-Kee; Sulaiman, Syuhaida; Lum, Chai-See; Syed-Omar, Syarifah-Faridah; AbuBakar, Sazaly

    2015-01-01

    HPS is a potentially life-threatening histiocytic disorder that has been described in various viral infections including dengue. Its involvement in severe and fatal dengue is probably more common but is presently under recognized. A 38-year-old female was admitted after 5 days of fever. She was deeply jaundiced, leukopenic and thrombocytopenic. Marked elevation of transaminases, hyperbilirubinemia and hypoalbuminemia were observed. She had deranged INR values and prolonged aPTT accompanied with hypofibrinogenemia. She also had splenomegaly. She was positive for dengue IgM. Five days later she became polyuric and CT brain image showed gross generalized cerebral edema. Her conditions deteriorated by day 9, became confused with GCS of 9/15. Her BMAT showed minimal histiocytes. Her serum ferritin level peaked at 13,670.00 µg/mL and her sCD163 and sCD25 values were markedly elevated at 4750.00 ng/mL and 4191.00 pg/mL, respectively. She succumbed to the disease on day 10 and examination of her tissues showed the presence of dengue virus genome in the bone marrow. It is described here, a case of fatal dengue with clinical features of HPS. Though BMAT results did not show the presence of macrophage hemophagocytosis, other laboratory features were consistent with HPS especially marked elevation of ferritin, sCD163 and sCD25. Detection of dengue virus in the patient's bone marrow, fifteen days after the onset of fever was also consistent with the suggestion that the HPS is associated with dengue virus infection. The findings highlight HPS as a possible complication leading to severe dengue and revealed persistent dengue virus infection of the bone marrow. Detection of HPS markers; ferritin, sCD163 and sCD25, therefore, should be considered for early recognition of HPS-associated dengue.

  2. Metabolic syndrome in patients with chronic hepatitis C virus genotype 1 infection who do not have obesity or type 2 diabetes

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    Lucivalda Pereira Magalhães Oliveira

    2012-01-01

    Full Text Available OBJECTIVE: The individual components of metabolic syndrome may be independent predictors of mortality in patients with liver disease. We aimed to evaluate the prevalence of metabolic syndrome and its related components in hepatitis C virus-infected patients who are not obese and do not have type 2 diabetes. METHODS: This cross-sectional study included 125 patients infected with hepatitis C virus genotype 1. Metabolic syndrome was defined according to the International Diabetes Federation. Anthropometric data were measured according to standardized procedures. Bioimpedance analysis was performed on all patients. RESULTS: Metabolic syndrome was diagnosed in 21.6% of patients. Of the subjects with metabolic syndrome, 59.3% had hypertension, 77.8% had insulin resistance, 85.2% were overweight, 48.1% had a high waist circumference, 85.2% had an increased body fat percentage, and 92.3% had an elevated waist:hip ratio. In the bivariate analysis, female sex (OR 2.58; 95% CI: 1.09-6.25, elevated gamma-glutamyl transferase (γGT (OR 2.63; 95% CI: 1.04-7.29, elevated fasting glucose (OR 8.05; 95% CI: 3.17-21.32, low HDL cholesterol (OR 2.80; 95% CI: 1.07-7.16, hypertriglyceridemia (OR 7.91; 95% CI: 2.88-22.71, elevated waist circumference (OR 10.33; 95% CI: 3.72-30.67, overweight (OR 11.33; 95% CI: 3.97-41.07, and increased body fat percentage (OR 8.34; 95% CI: 2.94-30.08 were independent determinants of metabolic syndrome. Using the final multivariate regression model, similar results were observed for abdominal fat (OR 9.98; 95% CI: 2.63-44.41 and total body fat percentage (OR 8.73; 95% CI: 2.33-42.34. However, metabolic syndrome risk was also high for those with blood glucose >5.55 mmol/L or HDL cholesterol <0.9 mmol/L (OR 16.69; 95% CI: 4.64-76.35; OR 7.23; 95% CI: 1.86-32.63, respectively. CONCLUSION: Metabolic syndrome is highly prevalent among hepatitis C virus-infected patients without type 2 diabetes or obesity. Metabolic syndrome was

  3. Absence of evidence of Xenotropic Murine Leukemia Virus-related virus infection in persons with Chronic Fatigue Syndrome and healthy controls in the United States

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    Switzer William M

    2010-07-01

    Full Text Available Abstract Background XMRV, a xenotropic murine leukemia virus (MuLV-related virus, was recently identified by PCR testing in 67% of persons with chronic fatigue syndrome (CFS and in 3.7% of healthy persons from the United States. To investigate the association of XMRV with CFS we tested blood specimens from 51 persons with CFS and 56 healthy persons from the US for evidence of XMRV infection by using serologic and molecular assays. Blinded PCR and serologic testing were performed at the US Centers for Disease Control and Prevention (CDC and at two additional laboratories. Results Archived blood specimens were tested from persons with CFS defined by the 1994 international research case definition and matched healthy controls from Wichita, Kansas and metropolitan, urban, and rural Georgia populations. Serologic testing at CDC utilized a Western blot (WB assay that showed excellent sensitivity to MuLV and XMRV polyclonal or monoclonal antibodies, and no reactivity on sera from 121 US blood donors or 26 HTLV-and HIV-infected sera. Plasma from 51 CFS cases and plasma from 53 controls were all WB negative. Additional blinded screening of the 51 cases and 53 controls at the Robert Koch Institute using an ELISA employing recombinant Gag and Env XMRV proteins identified weak seroreactivity in one CFS case and a healthy control, which was not confirmed by immunofluorescence. PCR testing at CDC employed a gag and a pol nested PCR assay with a detection threshold of 10 copies in 1 ug of human DNA. DNA specimens from 50 CFS patients and 56 controls and 41 US blood donors were all PCR-negative. Blinded testing by a second nested gag PCR assay at the Blood Systems Research Institute was also negative for DNA specimens from the 50 CFS cases and 56 controls. Conclusions We did not find any evidence of infection with XMRV in our U.S. study population of CFS patients or healthy controls by using multiple molecular and serologic assays. These data do not support an

  4. Protection against Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection through Passive Transfer of PRRSV-Neutralizing Antibodies Is Dose Dependent▿ †

    OpenAIRE

    Lopez, O. J.; Oliveira, M. F.; Garcia, E. Alvarez; Kwon, B. J.; Doster, A.; Osorio, F. A.

    2007-01-01

    Previous work in our laboratory demonstrated that passive transfer of porcine reproductive and respiratory syndrome virus (PRRSV)-neutralizing antibodies (NA) protected pregnant sows against reproductive failure and conferred sterilizing immunity in sows and offspring. We report here on the dose requirement for protection by passive transfer with NA in young weaned pigs. The presence of a 1:8 titer of PRRSV-NA in serum consistently protected pigs against viremia. Nevertheless, their lungs, to...

  5. Consensus on context-specific strategies for reducing the stigma of human immunodeficiency virus/acquired immunodeficiency syndrome in Zambézia Province, Mozambique

    OpenAIRE

    Mukolo, Abraham; Torres, Isabel; Bechtel, Ruth M.; Sidat, Mohsin; Vergara, Alfredo E.

    2014-01-01

    Stigma has been implicated in poor outcomes of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) care. Reducing stigma is important for HIV prevention and long-term treatment success. Although stigma reduction interventions are conducted in Mozambique, little is known about the current nature of stigma and the efficacy and effectiveness of stigma reduction initiatives. We describe action research to generate consensus on critical characteristics of HIV stigma and an...

  6. An unusual case of primary human immunodeficiency virus infection presenting as mononucleosis-like syndrome and acute aseptic meningoencephalitis. Report of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Marcelo Corti

    2014-01-01

    Full Text Available Clinical presentation of primary human immunodeficiency virus (HIV infection includes a wide spectrum of manifestations from asymptomatic infection to a symptomatic and severe illness. Central nervous system involvement should be always considered as a severe clinical form of primary HIV infection. Physicians should be aware to the broad clinical spectrum of primary HIV infection. We report a case of a female with diagnosis of mononucleosis-like syndrome and acute aseptic meningoencephalitis during primary HIV infection.

  7. Acquired immunodeficiency syndrome/human immunodeficiency virus knowledge, attitudes, and practices, and use of healthcare services among rural migrants: a cross-sectional study in China

    OpenAIRE

    Wang, Ying; Cochran, Christopher; Xu, Peng; Shen, Jay J; Zeng, Gang; Xu, Yanjun; Sun, Mei; Li, Chengyue; Li, Xiaohong; Chang, Fengshui; Lu, Jun; Hao, Mo; Lu, Fan

    2014-01-01

    Background Today’s rapid growth of migrant populations has been a major contributor to the human immunodeficiency virus (HIV) epidemic. However, relatively few studies have focused on HIV/acquired immunodeficiency syndrome (AIDS)-related knowledge, attitudes, and practice among rural-to-urban migrants in China. This cross-sectional study was to assess HIV/AIDS-related knowledge and perceptions, including knowledge about reducing high-risk sex. Methods Two-phase stratified cluster sampling was...

  8. Infection of growing swine with porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae — Effects on growth, serum metabolites, and insulin-like growth factor-I.

    OpenAIRE

    Roberts, N. Elizabeth; Almond, Glen W.

    2003-01-01

    This study evaluated the influence of concomitant infections with porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae on growth performance, serum metabolite concentrations, and serum insulin-like growth factor-I (IGF-I) in growing pigs. Twenty-two barrows (10 weeks of age) were treated with either an intranasal administration of PRRSV and an intratracheal infusion of M. hyopneumoniae (treatment; n = 8) or a sham inoculation with medium (sham; n = 8), or w...

  9. Complete Genome Sequence of a Recombinant NADC30-Like Strain, SCnj16, of Porcine Reproductive and Respiratory Syndrome Virus in Southwestern China

    Science.gov (United States)

    Kang, Runmin; Xie, Bo; Tian, Yiming; Yang, Xin; Yu, Jifeng

    2018-01-01

    ABSTRACT The NADC30-like strains of porcine reproductive and respiratory syndrome virus (PRRSV) are characterized by a 131-amino-acid deletion in nonstructural protein 2 (NSP2). Here, we report the complete genome sequence of a recombinant NADC30-like PRRSV strain, SCnj16, that exhibits the molecular marker of the Chinese highly pathogenic PRRSV (HP-PRRSV) in NSP2. PMID:29439029

  10. Multisubunit DNA-Dependent RNA Polymerases from Vaccinia Virus and Other Nucleocytoplasmic Large-DNA Viruses: Impressions from the Age of Structure.

    Science.gov (United States)

    Mirzakhanyan, Yeva; Gershon, Paul D

    2017-09-01

    The past 17 years have been marked by a revolution in our understanding of cellular multisubunit DNA-dependent RNA polymerases (MSDDRPs) at the structural level. A parallel development over the past 15 years has been the emerging story of the giant viruses, which encode MSDDRPs. Here we link the two in an attempt to understand the specialization of multisubunit RNA polymerases in the domain of life encompassing the large nucleocytoplasmic DNA viruses (NCLDV), a superclade that includes the giant viruses and the biochemically well-characterized poxvirus vaccinia virus. The first half of this review surveys the recently determined structural biology of cellular RNA polymerases for a microbiology readership. The second half discusses a reannotation of MSDDRP subunits from NCLDV families and the apparent specialization of these enzymes by virus family and by subunit with regard to subunit or domain loss, subunit dissociability, endogenous control of polymerase arrest, and the elimination/customization of regulatory interactions that would confer higher-order cellular control. Some themes are apparent in linking subunit function to structure in the viral world: as with cellular RNA polymerases I and III and unlike cellular RNA polymerase II, the viral enzymes seem to opt for speed and processivity and seem to have eliminated domains associated with higher-order regulation. The adoption/loss of viral RNA polymerase proofreading functions may have played a part in matching intrinsic mutability to genome size. Copyright © 2017 American Society for Microbiology.

  11. Structure of an antibody in complex with its mucin domain linear epitope that is protective against Ebola virus.

    Science.gov (United States)

    Olal, Daniel; Kuehne, Ana I; Bale, Shridhar; Halfmann, Peter; Hashiguchi, Takao; Fusco, Marnie L; Lee, Jeffrey E; King, Liam B; Kawaoka, Yoshihiro; Dye, John M; Saphire, Erica Ollmann

    2012-03-01

    Antibody 14G7 is protective against lethal Ebola virus challenge and recognizes a distinct linear epitope in the prominent mucin-like domain of the Ebola virus glycoprotein GP. The structure of 14G7 in complex with its linear peptide epitope has now been determined to 2.8 Å. The structure shows that this GP sequence forms a tandem β-hairpin structure that binds deeply into a cleft in the antibody-combining site. A key threonine at the apex of one turn is critical for antibody interaction and is conserved among all Ebola viruses. This work provides further insight into the mechanism of protection by antibodies that target the protruding, highly accessible mucin-like domain of Ebola virus and the structural framework for understanding and characterizing candidate immunotherapeutics.

  12. Ecology, Genetic Diversity, and Phylogeographic Structure of Andes Virus in Humans and Rodents in Chile▿

    Science.gov (United States)

    Medina, Rafael A.; Torres-Perez, Fernando; Galeno, Hector; Navarrete, Maritza; Vial, Pablo A.; Palma, R. Eduardo; Ferres, Marcela; Cook, Joseph A.; Hjelle, Brian

    2009-01-01

    Andes virus (ANDV) is the predominant etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in southern South America. In Chile, serologically confirmed human hantavirus infections have occurred throughout a wide latitudinal distribution extending from the regions of Valparaíso (32 to 33°S) to Aysén (46°S) in southern Patagonia. In this study, we found seropositive rodents further north in the Coquimbo region (30°S) in Chile. Rodent seroprevalence was 1.4%, with Oligoryzomys longicaudatus displaying the highest seroprevalence (5.9%), followed by Abrothrix longipilis (1.9%) and other species exhibiting ≤0.6% seropositivity. We sequenced partial ANDV small (S) segment RNA from 6 HCPS patients and 32 rodents of four different species collected throughout the known range of hantavirus infection in Chile. Phylogenetic analyses showed two major ANDV South (ANDV Sout) clades, congruent with two major Chilean ecoregions, Mediterranean (Chilean matorral [shrubland]) and Valdivian temperate forest. Human and rodent samples grouped according to geographic location. Phylogenetic comparative analyses of portions of S and medium segments (encoding glycoproteins Gn and Gc) from a subset of rodent specimens exhibited similar topologies, corroborating two major ANDV Sout clades in Chile and suggesting that yet unknown factors influence viral gene flow and persistence throughout the two Chilean ecoregions. Genetic algorithms for recombination detection identified recombination events within the S segment. Molecular demographic analyses showed that the virus is undergoing purifying selection and demonstrated a recent exponential growth in the effective number of ANDV Sout infections in Chile that correlates with the increased number of human cases reported. Although we determined virus sequences from four rodent species, our results confirmed O. longicaudatus as the primary ANDV Sout reservoir in Chile. While evidence of geographic differentiation exists, a single

  13. Ecology, genetic diversity, and phylogeographic structure of andes virus in humans and rodents in Chile.

    Science.gov (United States)

    Medina, Rafael A; Torres-Perez, Fernando; Galeno, Hector; Navarrete, Maritza; Vial, Pablo A; Palma, R Eduardo; Ferres, Marcela; Cook, Joseph A; Hjelle, Brian

    2009-03-01

    Andes virus (ANDV) is the predominant etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in southern South America. In Chile, serologically confirmed human hantavirus infections have occurred throughout a wide latitudinal distribution extending from the regions of Valparaíso (32 to 33 degrees S) to Aysén (46 degrees S) in southern Patagonia. In this study, we found seropositive rodents further north in the Coquimbo region (30 degrees S) in Chile. Rodent seroprevalence was 1.4%, with Oligoryzomys longicaudatus displaying the highest seroprevalence (5.9%), followed by Abrothrix longipilis (1.9%) and other species exhibiting Chile. Phylogenetic analyses showed two major ANDV South (ANDV Sout) clades, congruent with two major Chilean ecoregions, Mediterranean (Chilean matorral [shrubland]) and Valdivian temperate forest. Human and rodent samples grouped according to geographic location. Phylogenetic comparative analyses of portions of S and medium segments (encoding glycoproteins Gn and Gc) from a subset of rodent specimens exhibited similar topologies, corroborating two major ANDV Sout clades in Chile and suggesting that yet unknown factors influence viral gene flow and persistence throughout the two Chilean ecoregions. Genetic algorithms for recombination detection identified recombination events within the S segment. Molecular demographic analyses showed that the virus is undergoing purifying selection and demonstrated a recent exponential growth in the effective number of ANDV Sout infections in Chile that correlates with the increased number of human cases reported. Although we determined virus sequences from four rodent species, our results confirmed O. longicaudatus as the primary ANDV Sout reservoir in Chile. While evidence of geographic differentiation exists, a single cosmopolitan lineage of ANDV Sout remains the sole etiologic agent for HCPS in Chile.

  14. Hantavirus pulmonary syndrome (rio Mamore virus) in the peruvian Amazon region

    OpenAIRE

    Mamani, Enrique; Centro Nacional de Salud Pública. Instituto Nacional de Salud. Lima, Perú. biólogo.; García, María P.; Centro Nacional de Salud Pública. Instituto Nacional de Salud. Lima, Perú. tecnólogo médico.; Miraval, María L.; Centro Nacional de Salud Pública. Instituto Nacional de Salud. Lima, Perú. médico anátomo-patólogo.; Valencia, Pedro; Centro Nacional de Salud Pública. Instituto Nacional de Salud. Lima, Perú. Médico infectólogo.; Quino, Alberto H.; Hospital Regional de Loreto, Gobierno Regional de Loreto. Loreto, Perú. médico intensivista.; Álvarez, Carlos; Unidad de Análisis y Generación de Evidencias en Salud Pública. Instituto Nacional de Salud. Lima, Perú. médico anátomo-patólogo.; Donaires, Luis F.; Dirección Regional de Salud de Loreto, Gobierno Regional de Loreto. Loreto, Perú. médico epidemiólogo.

    2014-01-01

    Hantavirus infection is a viral zoonotic infection borne by rodents which most letal form clinical is the Hantavirus Pulmonary Syndrome (SPH, Spanish abbreviation). The Mamore River variant originates in South America and was found in rodents without any association to human diseases. Two cases of SPH were identified in the Peruvian Amazon region in November 2011. In both cases, a molecular diagnostic testing was conducted by the Instituto Nacional de Salud from Peru. A phylogenetic analy...

  15. Visualization of the structures of the hepatitis C virus replication complex

    International Nuclear Information System (INIS)

    Chan, Shih-Ching; Lo, Shih-Yen; Liou, Je-Wen; Lin, Min-Ching; Syu, Ciao-Ling; Lai, Meng-Jiun; Chen, Yi- Cheng; Li, Hui-Chun

    2011-01-01

    Research highlights: → Lipid rafts are known to play an important role in virus entry and virus assembly of many viruses. → However, HCV is the first example of the association of lipid raft with viral RNA replication. → Our results in this manuscript demonstrate that purified HCV RCs with associated lipid raft membrane appeared as distinct particles of around 0.7 um under EM and AFM. → Knockdown of proteins associated with lipid raft suppressed the HCV replication and reduced the number of these particles. → To our knowledge, structures of HCV RCs were demonstrated at its first time in this manuscript. -- Abstract: Hepatitis C viral RNA synthesis has been demonstrated to occur on a lipid raft membrane structure. Lipid raft membrane fraction purified by membrane flotation analysis was observed using transmission electron microscopy and atomic force microscopy. Particles around 0.7 um in size were found in lipid raft membrane fraction purified from hepatitis C virus (HCV) replicon but not their parental HuH7 cells. HCV NS5A protein was associated with these specialized particles. After several cycles of freezing-thawing, these particles would fuse into larger sizes up to 10 um. Knockdown of seven proteins associated with lipid raft (VAPA, COPG, RAB18, COMT, CDC42, DPP4, and KDELR2) of HCV replicon cells reduced the observed number of these particles and suppressed the HCV replication. Results in this study indicated that HCV replication complexes with associated lipid raft membrane form distinct particle structures of around 0.7 um as observed from transmission electron microscopy and atomic force microscopy.

  16. Structural insights into viral determinants of nematode mediated Grapevine fanleaf virus transmission.

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    Pascale Schellenberger

    2011-05-01

    Full Text Available Many animal and plant viruses rely on vectors for their transmission from host to host. Grapevine fanleaf virus (GFLV, a picorna-like virus from plants, is transmitted specifically by the ectoparasitic nematode Xiphinema index. The icosahedral capsid of GFLV, which consists of 60 identical coat protein subunits (CP, carries the determinants of this specificity. Here, we provide novel insight into GFLV transmission by nematodes through a comparative structural and functional analysis of two GFLV variants. We isolated a mutant GFLV strain (GFLV-TD poorly transmissible by nematodes, and showed that the transmission defect is due to a glycine to aspartate mutation at position 297 (Gly297Asp in the CP. We next determined the crystal structures of the wild-type GFLV strain F13 at 3.0 Å and of GFLV-TD at 2.7 Å resolution. The Gly297Asp mutation mapped to an exposed loop at the outer surface of the capsid and did not affect the conformation of the assembled capsid, nor of individual CP molecules. The loop is part of a positively charged pocket that includes a previously identified determinant of transmission. We propose that this pocket is a ligand-binding site with essential function in GFLV transmission by X. index. Our data suggest that perturbation of the electrostatic landscape of this pocket affects the interaction of the virion with specific receptors of the nematode's feeding apparatus, and thereby severely diminishes its transmission efficiency. These data provide a first structural insight into the interactions between a plant virus and a nematode vector.

  17. Detection of Severe Fever with Thrombocytopenia Syndrome Virus from Wild Animals and Ixodidae Ticks in the Republic of Korea.

    Science.gov (United States)

    Oh, Sung-Suck; Chae, Jeong-Byoung; Kang, Jun-Gu; Kim, Heung-Chul; Chong, Sung-Tae; Shin, Jeong-Hwa; Hur, Moon-Suk; Suh, Jae-Hwa; Oh, Myoung-Don; Jeong, Soo-Myoung; Shin, Nam-Shik; Choi, Kyoung-Seong; Chae, Joon-Seok

    2016-06-01

    Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a novel bunyavirus reported to be endemic to central-northeastern China, southern Japan, and the Republic of Korea (ROK). To investigate SFTSV infections, we collected serum samples and ticks from wild animals. Using serum samples and ticks, SFTSV-specific genes were amplified by one-step RT-PCR and nested PCR and sequenced. Indirect immunofluorescence assay (IFA) was performed to analyze virus-specific antibody levels in wild animals. Serum samples were collected from a total of 91 animals: 21 Korean water deer (KWD), 3 Siberian roe deer, 5 gorals, 7 raccoon dogs, 54 wild boars (WBs), and 1 carrion crow. The SFTSV infection rate in wild animals was 3.30% (3 of 91 animals: 1 KWD and 2 WBs). The seropositive rate was 6.59% (6 of 91 animals: 5 KWD and 1 WB). A total of 891 ticks (3 species) were collected from 65 wild animals (9 species). Of the attached tick species, Haemaphysalis longicornis (74.86%) was the most abundant, followed by Haemaphysalis flava (20.20%) and Ixodes nipponensis (4.94%). The average minimum infection rate (MIR) of SFTSV in ticks was 4.98%. The MIRs of H. longicornis, H. flava, and I. nipponensis were 4.51%, 2.22%, and 22.73%, respectively. The MIRs of larvae, nymphs, and adult ticks were 0.68%, 6.88%, and 5.53%, respectively. In addition, the MIRs of fed and unfed ticks were 4.67% and 4.96%, respectively. We detected a low SFTSV infection rate in wild animals, no differences in SFTSV infection rate with respect to bloodsucking in ticks, and SFTSV infection for all developmental stages of ticks. This is the first report describing the detection of SFTSV in wild animals in the ROK.

  18. The Mechanism of Synchronous Precise Regulation of Two Shrimp White Spot Syndrome Virus Targets by a Viral MicroRNA

    Science.gov (United States)

    He, Yaodong; Ma, Tiantian; Zhang, Xiaobo

    2017-01-01

    MicroRNAs (miRNAs), important factors in animal innate immunity, suppress the expressions of their target genes by binding to target mRNA’s 3′ untranslated regions (3′UTRs). However, the mechanism of synchronous regulation of multiple targets by a single miRNA remains unclear. In this study, the interaction between a white spot syndrome virus (WSSV) miRNA (WSSV-miR-N32) and its two viral targets (wsv459 and wsv322) was characterized in WSSV-infected shrimp. The outcomes indicated that WSSV-encoded miRNA (WSSV-miR-N32) significantly inhibited virus infection by simultaneously targeting wsv459 and wsv322. The silencing of wsv459 or wsv322 by siRNA led to significant decrease of WSSV copies in shrimp, showing that the two viral genes were required for WSSV infection. WSSV-miR-N32 could mediate 5′–3′ exonucleolytic digestion of its target mRNAs, which stopped at the sites of target mRNA 3′UTRs close to the sequence complementary to the miRNA seed sequence. The complementary bases (to the target mRNA sequence) of a miRNA 9th–18th non-seed sequence were essential for the miRNA targeting. Therefore, our findings presented novel insights into the mechanism of miRNA-mediated suppression of target gene expressions, which would be helpful for understanding the roles of miRNAs in innate immunity of invertebrate. PMID:29230209

  19. Variable RNA expression from recently acquired, endogenous viral elements (EVE) of white spot syndrome virus (WSSV) in shrimp.

    Science.gov (United States)

    Utari, Heny Budi; Soowannayan, Chumporn; Flegel, Timothy W; Whityachumnarnkul, Boonsirm; Kruatrachue, Maleeya

    2017-11-01

    The viral accommodation hypothesis proposes that endogenous viral elements (EVE) from both RNA and DNA viruses are being continually integrated into the shrimp genome by natural host processes and that they can result in tolerance to viral infection by fortuitous production of antisense, immunospecific RNA (imRNA). Thus, we hypothesized that previously reported microarray results for the presence of white spot syndrome virus (WSSV) open reading frames (ORFs) formerly called 151, 366 and 427 in a domesticated giant tiger shrimp (Penaeus monodon) breeding stock might have represented expression from EVE, since the stock had shown uninterrupted freedom from white spot disease (WSD) for many generations. To test this hypothesis, 128 specimens from a current stock generation were confirmed for freedom from WSSV infection using two nested PCR detection methods. Subsequent nested-PCR testing revealed 33/128 specimens (26%) positive for at least one of the ORF at very high sequence identity (95-99%) to extant WSSV. Positive results for ORF 366 (now known to be a fragment of the WSSV capsid protein gene) dominated (28/33 = 84.8%), so 9 arbitrarily selected 366-positive specimens were tested by strand-specific, nested RT-PCR using DNase-treated RNA templates. This revealed variable RNA expression in individual shrimp including no RNA transcripts (n = 1), sense transcripts only (n = 1), antisense transcripts only (n = 2) or transcripts of both sense (n = 5). The latter 7 expression products indicated specimens producing putative imRNA. The variable types and numbers of the EVE and the variable RNA expression (including potential imRNA) support predictions of the viral accommodation hypothesis that EVE are randomly produced and expressed. Positive nested PCR test results for EVE of ORF 366 using DNA templates derived from shrimp sperm (germ cells), indicated that they were heritable. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Gene expression profiling in gill tissues of White spot syndrome virus infected black tiger shrimp Penaeus monodon by DNA microarray.

    Science.gov (United States)

    Shekhar, M S; Gomathi, A; Gopikrishna, G; Ponniah, A G

    2015-06-01

    White spot syndrome virus (WSSV) continues to be the most devastating viral pathogen infecting penaeid shrimp the world over. The genome of WSSV has been deciphered and characterized from three geographical isolates and significant progress has been made in developing various molecular diagnostic methods to detect the virus. However, the information on host immune gene response to WSSV pathogenesis is limited. Microarray analysis was carried out as an approach to analyse the gene expression in black tiger shrimp Penaeus monodon in response to WSSV infection. Gill tissues collected from the WSSV infected shrimp at 6, 24, 48 h and moribund stage were analysed for differential gene expression. Shrimp cDNAs of 40,059 unique sequences were considered for designing the microarray chip. The Cy3-labeled cRNA derived from healthy and WSSV-infected shrimp was subjected to hybridization with all the DNA spots in the microarray which revealed 8,633 and 11,147 as up- and down-regulated genes respectively at different time intervals post infection. The altered expression of these numerous genes represented diverse functions such as immune response, osmoregulation, apoptosis, nucleic acid binding, energy and metabolism, signal transduction, stress response and molting. The changes in gene expression profiles observed by microarray analysis provides molecular insights and framework of genes which are up- and down-regulated at different time intervals during WSSV infection in shrimp. The microarray data was validated by Real Time analysis of four differentially expressed genes involved in apoptosis (translationally controlled tumor protein, inhibitor of apoptosis protein, ubiquitin conjugated enzyme E2 and caspase) for gene expression levels. The role of apoptosis related genes in WSSV infected shrimp is discussed herein.

  1. Transcriptome analysis of Kuruma shrimp (Marsupenaeus japonicus) hepatopancreas in response to white spot syndrome virus (WSSV) under experimental infection.

    Science.gov (United States)

    Zhong, Shengping; Mao, Yong; Wang, Jun; Liu, Min; Zhang, Man; Su, Yongquan

    2017-11-01

    Kuruma shrimp (Marsupenaeus japonicus) is one of the most valuable crustacean species in capture fisheries and mariculture in the Indo-West Pacific. White spot syndrome virus (WSSV) is a highly virulent pathogen which has seriously threatened Kuruma shrimp aquaculture sector. However, little information is available in relation to underlying mechanisms of host-virus interaction in Kuruma shrimp. In this study, we performed a transcriptome analysis from the hepatopancreas of Kuruma shrimp challenged by WSSV, using Illumina-based RNA-Seq. A total of 39,084,942 pair end (PE) reads, including 19,566,190 reads from WSSV-infected group and 19,518,752 reads from non-infected (control) group, were obtained and assembled into 33,215 unigenes with an average length of 503.7 bp and N50 of 601 bp. Approximately 17,000 unigenes were predicted and classified based on homology search, gene ontology, clusters of orthologous groups of proteins, and biological pathway mapping. Differentially expressed genes (DEGs), including 2150 up-regulated and 1931 down-regulated, were found. Among those, 805 DEGs were identified and categorized into 14 groups based on their possible functions. Many genes associated with JAK-STAT signaling pathways, Integrin-mediated signal transduction, Ras signaling pathways, apoptosis and phagocytosis were positively modified after WSSV challenge. The proteolytic cascades including Complement-like activation and Hemolymph coagulations likely participated in antiviral immune response. The transcriptome data from hepatopancreas of Kuruma shrimp under WSSV challenge provided comprehensive information for identifying novel immune related genes in this valuable crustacean species despite the absence of the genome database of crustaceans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Interaction of the Small GTPase Cdc42 with Arginine Kinase Restricts White Spot Syndrome Virus in Shrimp.

    Science.gov (United States)

    Xu, Ji-Dong; Jiang, Hai-Shan; Wei, Tian-Di; Zhang, Ke-Yi; Wang, Xian-Wei; Zhao, Xiao-Fan; Wang, Jin-Xing

    2017-03-01

    Many types of small GTPases are widely expressed in eukaryotes and have different functions. As a crucial member of the Rho GTPase family, Cdc42 serves a number of functions, such as regulating cell growth, migration, and cell movement. Several RNA viruses employ Cdc42-hijacking tactics in their target cell entry processes. However, the function of Cdc42 in shrimp antiviral immunity is not clear. In this study, we identified a Cdc42 protein in the kuruma shrimp ( Marsupenaeus japonicus ) and named it Mj Cdc42. Mj Cdc42 was upregulated in shrimp challenged by white spot syndrome virus (WSSV). The knockdown of Mj Cdc42 and injection of Cdc42 inhibitors increased the proliferation of WSSV. Further experiments determined that Mj Cdc42 interacted with an arginine kinase ( Mj AK). By analyzing the binding activity and enzyme activity of Mj AK and its mutant, Δ Mj AK, we found that Mj AK could enhance the replication of WSSV in shrimp. Mj AK interacted with the envelope protein VP26 of WSSV. An inhibitor of AK activity, quercetin, could impair the function of Mj AK in WSSV replication. Further study demonstrated that the binding of Mj Cdc42 and Mj AK depends on Cys 271 of Mj AK and suppresses the WSSV replication-promoting effect of Mj AK. By interacting with the active site of Mj AK and suppressing its enzyme activity, Mj Cdc42 inhibits WSSV replication in shrimp. Our results demonstrate a new function of Cdc42 in the cellular defense against viral infection in addition to the regulation of actin and phagocytosis, which has been reported in previous studies. IMPORTANCE The interaction of Cdc42 with arginine kinase plays a crucial role in the host defense against WSSV infection. This study identifies a new mechanism of Cdc42 in innate immunity and enriches the knowledge of the antiviral innate immunity of invertebrates. Copyright © 2017 American Society for Microbiology.

  3. White spot syndrome virus induces metabolic changes resembling the warburg effect in shrimp hemocytes in the early stage of infection.

    Science.gov (United States)

    Chen, I-Tung; Aoki, Takashi; Huang, Yun-Tzu; Hirono, Ikuo; Chen, Tsan-Chi; Huang, Jiun-Yan; Chang, Geen-Dong; Lo, Chu-Fang; Wang, Han-Ching

    2011-12-01

    The Warburg effect is an abnormal glycolysis response that is associated with cancer cells. Here we present evidence that metabolic changes resembling the Warburg effect are induced by a nonmammalian virus. When shrimp were infected with white spot syndrome virus (WSSV), changes were induced in several metabolic pathways related to the mitochondria. At the viral genome replication stage (12 h postinfection [hpi]), glucose consumption and plasma lactate concentration were both increased in WSSV-infected shrimp, and the key enzyme of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PDH), showed increased activity. We also found that at 12 hpi there was no alteration in the ADP/ATP ratio and that oxidative stress was lower than that in uninfected controls. All of these results are characteristic of the Warburg effect as it is present in mammals. There was also a significant decrease in triglyceride concentration starting at 12 hpi. At the late stage of the infection cycle (24 hpi), hemocytes of WSSV-infected shrimp showed several changes associated with cell death. These included the induction of mitochondrial membrane permeabilization (MMP), increased oxidative stress, decreased glucose consumption, and disrupted energy production. A previous study showed that WSSV infection led to upregulation of the voltage-dependent anion channel (VDAC), which is known to be involved in both the Warburg effect and MMP. Here we show that double-stranded RNA (dsRNA) silencing of the VDAC reduces WSSV-induced mortality and virion copy number. For these results, we hypothesize a model depicting the metabolic changes in host cells at the early and late stages of WSSV infection.

  4. tRNA-like structure regulates translation of Brome mosaic virus RNA.

    Science.gov (United States)

    Barends, Sharief; Rudinger-Thirion, Joëlle; Florentz, Catherine; Giegé, Richard; Pleij, Cornelis W A; Kraal, Barend

    2004-04-01

    For various groups of plant viruses, the genomic RNAs end with a tRNA-like structure (TLS) instead of the 3' poly(A) tail of common mRNAs. The actual function of these TLSs has long been enigmatic. Recently, however, it became clear that for turnip yellow mosaic virus, a tymovirus, the valylated TLS(TYMV) of the single genomic RNA functions as a bait for host ribosomes and directs them to the internal initiation site of translation (with N-terminal valine) of the second open reading frame for the polyprotein. This discovery prompted us to investigate whether the much larger TLSs of a different genus of viruses have a comparable function in translation. Brome mosaic virus (BMV), a bromovirus, has a tripartite RNA genome with a subgenomic RNA4 for coat protein expression. All four RNAs carry a highly conserved and bulky 3' TLS(BMV) (about 200 nucleotides) with determinants for tyrosylation. We discovered TLS(BMV)-catalyzed self-tyrosylation of the tyrosyl-tRNA synthetase but could not clearly detect tyrosine incorporation into any virus-encoded protein. We established that BMV proteins do not need TLS(BMV) tyrosylation for their initiation. However, disruption of the TLSs strongly reduced the translation of genomic RNA1, RNA2, and less strongly, RNA3, whereas coat protein expression from RNA4 remained unaffected. This aberrant translation could be partially restored by providing the TLS(BMV) in trans. Intriguingly, a subdomain of the TLS(BMV) could even almost fully restore translation to the original pattern. We discuss here a model with a central and dominant role for the TLS(BMV) during the BMV infection cycle.

  5. Field and laboratory evidence that Bungowannah virus, a recently recognised pestivirus, is the causative agent of the porcine myocarditis syndrome (PMC).

    Science.gov (United States)

    Finlaison, Deborah S; King, Katherine R; Frost, Melinda J; Kirkland, Peter D

    2009-05-12

    In 2003 an outbreak of sudden deaths occurred in 2-3-week-old piglets on a piggery in New South Wales, Australia. There was a marked increase in the birth of stillborn piglets and preweaning losses associated with a multifocal non-suppurative myocarditis with myonecrosis. The aim of this study was to review existing data and to undertake further investigations of specimens from naturally infected pigs to provide evidence to support the hypothesis that Bungowannah virus, a recently recognised pestivirus, causes the porcine myocarditis syndrome (PMC). Sera collected from gilts and sows from affected and unaffected units were tested for Bungowannah virus antibody by a peroxidase-linked assay and Bungowannah virus RNA by qRT-PCR in selected cases. Stillborn piglets from affected and an unaffected unit were also tested for Bungowannah virus antibody and RNA. Body fluid IgG levels and the incidence of myocardial lesions in these stillborn piglets are summarised. Tissue sections from stillborn piglets with myocarditis/myonecrosis were examined for Bungowannah virus RNA by in situ hybridisation. A clear temporal association between the occurrence of PMC on a unit or module and exposure to Bungowannah virus was identified by serological tests in both breeding aged animals and stillborn pigs. In addition, at the individual animal level on affected units, Bungowannah virus RNA was detected in stillborn piglets in large amounts by qRT-PCR and in association with myocardial lesions by in situ hybridisation. The examination of field material from cases of PMC by serology, qRT-PCR and in situ hybridisation provides strong indirect evidence that Bungowannah virus is the causative agent for PMC.

  6. Structural Basis for dsRNA Recognition by NS1 Protein of Influenza A Virus

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, A.; Wong, S; Yuan, Y

    2009-01-01

    Influenza A viruses are important human pathogens causing periodic pandemic threats. Nonstructural protein 1 (NS1) protein of influenza A virus (NS1A) shields the virus against host defense. Here, we report the crystal structure of NS1A RNA-binding domain (RBD) bound to a double-stranded RNA (dsRNA) at 1.7A. NS1A RBD forms a homodimer to recognize the major groove of A-form dsRNA in a length-independent mode by its conserved concave surface formed by dimeric anti-parallel alpha-helices. dsRNA is anchored by a pair of invariable arginines (Arg38) from both monomers by extensive hydrogen bonds. In accordance with the structural observation, isothermal titration calorimetry assay shows that the unique Arg38-Arg38 pair and two Arg35-Arg46 pairs are crucial for dsRNA binding, and that Ser42 and Thr49 are also important for dsRNA binding. Agrobacterium co-infiltration assay further supports that the unique Arg38 pair plays important roles in dsRNA binding in vivo.

  7. Structural and Functional Diversity of Plant Virus 3'-Cap-Independent Translation Enhancers (3'-CITEs).

    Science.gov (United States)

    Truniger, Verónica; Miras, Manuel; Aranda, Miguel A

    2017-01-01

    Most of the positive-strand RNA plant viruses lack the 5'-cap and/or the poly(A)-tail that act synergistically to stimulate canonical translation of cellular mRNAs. However, they have RNA elements in the 5'- or 3'-untranslated regions of their RNAs that are required for their cap-independent translation. Cap-independent translation enhancers (CITEs) have been identified in the genomic 3'-end of viruses belonging to the family Tombusviridae and the genus Luteovirus . Seven classes of 3'-CITEs have been described to date based on their different RNA structures. They generally control the efficient formation of the translation initiation complex by varying mechanisms. Some 3'-CITEs bind eukaryotic translation initiation factors, others ribosomal subunits, bridging these to the 5'-end by different mechanisms, often long-distance RNA-RNA interactions. As previously proposed and recently found in one case in nature, 3'-CITEs are functionally independent elements that are transferable through recombination between viral genomes, leading to potential advantages for virus multiplication. In this review, the knowledge on 3'-CITEs and their functioning is updated. We also suggest that there is local structural conservation in the regions interacting with eIF4E of 3'-CITEs belonging to different classes.

  8. Structural analysis of herpes simplex virus by optical super-resolution imaging

    Science.gov (United States)

    Laine, Romain F.; Albecka, Anna; van de Linde, Sebastian; Rees, Eric J.; Crump, Colin M.; Kaminski, Clemens F.

    2015-01-01

    Herpes simplex virus type-1 (HSV-1) is one of the most widespread pathogens among humans. Although the structure of HSV-1 has been extensively investigated, the precise organization of tegument and envelope proteins remains elusive. Here we use super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) in combination with a model-based analysis of single-molecule localization data, to determine the position of protein layers within virus particles. We resolve different protein layers within individual HSV-1 particles using multi-colour dSTORM imaging and discriminate envelope-anchored glycoproteins from tegument proteins, both in purified virions and in virions present in infected cells. Precise characterization of HSV-1 structure was achieved by particle averaging of purified viruses and model-based analysis of the radial distribution of the tegument proteins VP16, VP1/2 and pUL37, and envelope protein gD. From this data, we propose a model of the protein organization inside the tegument.

  9. Structural and Antigenic Definition of Hepatitis C Virus E2 Glycoprotein Epitopes Targeted by Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Giuseppe Sautto

    2013-01-01

    Full Text Available Hepatitis C virus (HCV is the major cause of chronic liver disease as well as the major indication for liver transplantation worldwide. Current standard of care is not completely effective, not administrable in grafted patients, and burdened by several side effects. This incomplete effectiveness is mainly due to the high propensity of the virus to continually mutate under the selective pressure exerted by the host immune response as well as currently administered antiviral drugs. The E2 envelope surface glycoprotein of HCV (HCV/E2 is the main target of the host humoral immune response and for this reason one of the major variable viral proteins. However, broadly cross-neutralizing monoclonal antibodies (mAbs directed against HCV/E2 represent a promising tool for the study of virus-host interplay as well as for the development of effective prophylactic and therapeutic approaches. In the last few years many anti-HCV/E2 mAbs have been evaluated in preclinical and clinical trials as possible candidate antivirals, particularly for administration in pre- and post-transplant settings. In this review we summarize the antigenic and structural characteristics of HCV/E2 determined through the use of anti-HCV/E2 mAbs, which, given the absence of a crystal structure of this glycoprotein, represent currently the best tool available.

  10. The association of metabolic syndrome and Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus type 1: The Persian Gulf Healthy Heart Study

    Directory of Open Access Journals (Sweden)

    Pazoki Raha

    2006-12-01

    Full Text Available Abstract Background The metabolic syndrome together with insulin resistance and their consequences are basic factors in pathogenesis of atherosclerosis. Chronic infections with herpes simplex virus type 1 (HSV-1, cytomegalovirus (CMV, and Chlamydia pneumoniae are associated with the development of atherosclerosis and coronary heart disease. The infectious aspects of metabolic syndrome have not been investigated. Methods In a cross-sectional, population-based study, we used National Cholesterol Education Program (NCEP-Adult Treatment Panel (ATP-III criteria in 1791 subjects, aged 25 years and over, selected by cluster random sampling in three Iranian ports in the northern Persian Gulf. Sera were analyzed for IgG antibodies to Chlamydia pneumoniae, HSV-1, Helicobacter pylori (H. pylori and CMV using ELISA. Results In multiple logistic regression analysis, of the infectious agents, CMV [OR = 1.81 (1.05–3.10; p = 0.03], H. pylori [OR = 1.50 (1.12–2.00; p = 0.007] and Chlamydia pneumoniae [OR = 1.69 (1.27–2.25; p Conclusion The metabolic syndrome, which occurs very frequently in the general population, has a significant association with prior infection with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus and herpes simplex virus type 1. Hypothesis about participation of infection in pathogenesis of metabolic syndrome should be investigated.

  11. Bioinformatics prediction of swine MHC class I epitopes from Porcine Reproductive and Respiratory Syndrome Virus

    DEFF Research Database (Denmark)

    Welner, Simon; Nielsen, Morten; Lund, Ole

    an effective CTL response against PRRSV, we have taken a bioinformatics approach to identify common PRRSV epitopes predicted to react broadly with predominant swine MHC (SLA) alleles. First, the genomic integrity and sequencing method was examined for 334 available complete PRRSV type 2 genomes leaving 104...... by the PopCover algorithm, providing a final list of 54 epitopes prioritized according to maximum coverage of PRRSV strains and SLA alleles. This bioinformatics approach provides a rational strategy for selecting peptides for a CTL-activating vaccine with broad coverage of both virus and swine diversity...

  12. Crystal Structure of the N-Terminal Half of the Traffic Controller UL37 from Herpes Simplex Virus 1

    Energy Technology Data Exchange (ETDEWEB)

    Koenigsberg, Andrea L.; Heldwein, Ekaterina E.; Sandri-Goldin, Rozanne M.

    2017-08-02

    Inner tegument protein UL37 is conserved among all three subfamilies of herpesviruses. Studies of UL37 homologs from two alphaherpesviruses, herpes simplex virus 1 (HSV-1) and pseudorabies virus (PRV), have suggested that UL37 plays an essential albeit poorly defined role in intracellular capsid trafficking. At the same time, HSV and PRV homologs cannot be swapped, which suggests that in addition to a conserved function, UL37 homologs also have divergent virus-specific functions. Accurate dissection of UL37 functions requires detailed maps in the form of atomic-resolution structures. Previously, we reported the crystal structure of the N-terminal half of UL37 (UL37N) from PRV. Here, we report the crystal structure of HSV-1 UL37N. Comparison of the two structures reveals that UL37 homologs differ in their overall shapes, distributions of surface charges, and locations of projecting loops. In contrast, the previously identified R2 surface region is structurally conserved. We propose that within the N-terminal half of UL37, functional conservation is centered within the R2 surface region, whereas divergent structural elements pinpoint regions mediating virus-specific functions and may engage different binding partners. Together, the two structures can now serve as templates for a structure-guided exploration of both conserved and virus-specific functions of UL37.

    IMPORTANCEThe ability to move efficiently within host cell cytoplasm is essential for replication in all viruses. It is especially important in the neuroinvasive alphaherpesviruses, such as human herpes simplex virus 1 (HSV-1), HSV-2, and veterinarian pseudorabies virus (PRV), that infect the peripheral nervous system and have to travel long distances along axons. Capsid movement in these viruses is controlled by capsid-associated tegument proteins, yet their specific roles have not yet been defined. Systematic exploration of the roles of tegument proteins in capsid trafficking requires

  13. Cardiac structure and function in Cushing's syndrome: a cardiac magnetic resonance imaging study.

    Science.gov (United States)

    Kamenický, Peter; Redheuil, Alban; Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe

    2014-11-01

    Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2-12 mo) after the treatment of hypercortisolism. Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism.

  14. Structural and functional characterization of Reston Ebola virus VP35 interferon inhibitory domain.

    Science.gov (United States)

    Leung, Daisy W; Shabman, Reed S; Farahbakhsh, Mina; Prins, Kathleen C; Borek, Dominika M; Wang, Tianjiao; Mühlberger, Elke; Basler, Christopher F; Amarasinghe, Gaya K

    2010-06-11

    Ebolaviruses are causative agents of lethal hemorrhagic fever in humans and nonhuman primates. Among the filoviruses characterized thus far, Reston Ebola virus (REBOV) is the only Ebola virus that is nonpathogenic to humans despite the fact that REBOV can cause lethal disease in nonhuman primates. Previous studies also suggest that REBOV is less effective at inhibiting host innate immune responses than Zaire Ebola virus (ZEBOV) or Marburg virus. Virally encoded VP35 protein is critical for immune suppression, but an understanding of the relative contributions of VP35 proteins from REBOV and other filoviruses is currently lacking. In order to address this question, we characterized the REBOV VP35 interferon inhibitory domain (IID) using structural, biochemical, and virological studies. These studies reveal differences in double-stranded RNA binding and interferon inhibition between the two species. These observed differences are likely due to increased stability and loss of flexibility in REBOV VP35 IID, as demonstrated by thermal shift stability assays. Consistent with this finding, the 1.71-A crystal structure of REBOV VP35 IID reveals that it is highly similar to that of ZEBOV VP35 IID, with an overall backbone r.m.s.d. of 0.64 A, but contains an additional helical element at the linker between the two subdomains of VP35 IID. Mutations near the linker, including swapping sequences between REBOV and ZEBOV, reveal that the linker sequence has limited tolerance for variability. Together with the previously solved ligand-free and double-stranded-RNA-bound forms of ZEBOV VP35 IID structures, our current studies on REBOV VP35 IID reinforce the importance of VP35 in immune suppression. Functional differences observed between REBOV and ZEBOV VP35 proteins may contribute to observed differences in pathogenicity, but these are unlikely to be the major determinant. However, the high level of similarity in structure and the low tolerance for sequence variability, coupled

  15. Structure of a Human Astrovirus Capsid-Antibody Complex and Mechanistic Insights into Virus Neutralization

    Energy Technology Data Exchange (ETDEWEB)

    Bogdanoff, Walter A.; Campos, Jocelyn; Perez, Edmundo I.; Yin, Lu; Alexander, David L.; DuBois, Rebecca M. (UCSC)

    2016-11-02

    ABSTRACT

    Human astroviruses (HAstVs) are a leading cause of viral diarrhea in young children, the immunocompromised, and the elderly. There are no vaccines or antiviral therapies against HAstV disease. Several lines of evidence point to the presence of protective antibodies in healthy adults as a mechanism governing protection against reinfection by HAstV. However, development of anti-HAstV therapies is hampered by the gap in knowledge of protective antibody epitopes on the HAstV capsid surface. Here, we report the structure of the HAstV capsid spike domain bound to the neutralizing monoclonal antibody PL-2. The antibody uses all six complementarity-determining regions to bind to a quaternary epitope on each side of the dimeric capsid spike. We provide evidence that the HAstV capsid spike is a receptor-binding domain and that the antibody neutralizes HAstV by blocking virus attachment to cells. We identify patches of conserved amino acids that overlap the antibody epitope and may comprise a receptor-binding site. Our studies provide a foundation for the development of therapies to prevent and treat HAstV diarrheal disease.

    IMPORTANCEHuman astroviruses (HAstVs) infect nearly every person in the world during childhood and cause diarrhea, vomiting, and fever. Despite the prevalence of this virus, little is known about how antibodies in healthy adults protect them against reinfection. Here, we determined the crystal structure of a complex of the HAstV capsid protein and a virus-neutralizing antibody. We show that the antibody binds to the outermost spike domain of the capsid, and we provide evidence that the antibody blocks virus attachment to human cells. Importantly, our findings suggest that a subunit-based vaccine focusing the immune system on the HAstV capsid spike domain could be effective in protecting children against HAstV disease.

  16. Molecular and structural characterization of fluorescent human parvovirus B19 virus-like particles

    International Nuclear Information System (INIS)

    Gilbert, Leona; Toivola, Jouni; White, Daniel; Ihalainen, Teemu; Smith, Wesley; Lindholm, Laura; Vuento, Matti; Oker-Blom, Christian

    2005-01-01

    Although sharing a T = 1 icosahedral symmetry with other members of the Parvoviridae family, it has been suggested that the fivefold channel of the human parvovirus B19 VP2 capsids is closed at its outside end. To investigate the possibility of placing a relatively large protein moiety at this site of B19, fluorescent virus-like particles (fVLPs) of B19 were developed. The enhanced green fluorescent protein (EGFP) was inserted at the N-terminus of the structural protein VP2 and assembly of fVLPs from this fusion protein was obtained. Electron microscopy revealed that these fluorescent protein complexes were very similar in size when compared to wild-type B19 virus. Further, fluorescence correlation spectroscopy showed that an average of nine EGFP domains were associated with these virus-like structures. Atomic force microscopy and immunoprecipitation studies showed that EGFP was displayed on the surface of these fVLPs. Confocal imaging indicated that these chimeric complexes were targeted to late endosomes when expressed in insect cells. The fVLPs were able to efficiently enter cancer cells and traffic to the nucleus via the microtubulus network. Finally, immunoglobulins present in human parvovirus B19 acute and past-immunity serum samples were able to detect antigenic epitopes present in these fVLPs. In summary, we have developed fluorescent virus-like nanoparticles displaying a large heterologous entity that should be of help to elucidate the mechanisms of infection and pathogenesis of human parvovirus B19. In addition, these B19 nanoparticles serve as a model in the development of targetable vehicles designed for delivery of biomolecules

  17. Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus

    DEFF Research Database (Denmark)

    Brinth, Louise S; Pors, Kirsten; Theibel, Ann C

    2015-01-01

    of postural orthostatic tachycardia syndrome (POTS) rested on finding a sustained heart rate increment of >30min(-1) (>40min(-1) in adolescents) or to levels >120min(-1) during orthostatic challenge. RESULTS: 35 women aged 23.3±7.1 years participated. Twenty-five had a high level of physical activity before...... vaccination and irregular periods were reported by all patients not on treatment with oral contraception. Serum bilirubin was below the lower detection limit in 17 patients. Twenty-one of the referred patients fulfilled the criteria for a diagnosis of POTS (60%, 95%CI 43-77%). All patients had orthostatic...

  18. Brief Report: CANTAB Performance and Brain Structure in Pediatric Patients with Asperger Syndrome

    Science.gov (United States)

    Kaufmann, Liane; Zotter, Sibylle; Pixner, Silvia; Starke, Marc; Haberlandt, Edda; Steinmayr-Gensluckner, Maria; Egger, Karl; Schocke, Michael; Weiss, Elisabeth M.; Marksteiner, Josef

    2013-01-01

    By merging neuropsychological (CANTAB/Cambridge Neuropsychological Test Automated Battery) and structural brain imaging data (voxel-based-morphometry) the present study sought to identify the neurocognitive correlates of executive functions in individuals with Asperger syndrome (AS) compared to healthy controls. Results disclosed subtle group…

  19. Testing the 8-syndrome structure of the child behavior checklist in 30 societies

    DEFF Research Database (Denmark)

    Ivanova, Masha Y; Dobrean, Anca; Dopfner, Manfred

    2007-01-01

    There is a growing need for multicultural collaboration in child mental health services, training, and research. To facilitate such collaboration, this study tested the 8-syndrome structure of the Child Behavior Checklist (CBCL) in 30 societies. Parents' CBCL ratings of 58,051 6- to 18-year-olds ...

  20. Testing the 8-Syndrome Structure of the Child Behavior Checklist in 30 Societies

    Science.gov (United States)

    Ivanova, Masha Y.; Dobrean, Anca; Dopfner, Manfred; Erol, Nese; Fombonne, Eric; Fonseca, Antonio Castro; Frigerio, Alessandra; Grietens, Hans; Hannesdottir, Helga; Kanbayashi, Yasuko; Lambert, Michael; Achenbach, Thomas M.; Larsson, Bo; Leung, Patrick; Liu, Xianchen; Minaei, Asghar; Mulatu, Mesfin S.; Novik, Torunn S.; Oh, Kyung Ja; Roussos, Alexandra; Sawyer, Michael; Simsek, Zeynep; Dumenci, Levent; Steinhausen, Hans-Christoph; Metzke, Christa Winkler; Wolanczyk, Tomasz; Yang, Hao-Jan; Zilber, Nelly; Zukauskiene, Rita; Verhulst, Frank C.; Rescorla, Leslie A.; Almqvist, Fredrik; Weintraub, Sheila; Bilenberg, Niels; Bird, Hector; Chen, Wei J.

    2007-01-01

    There is a growing need for multicultural collaboration in child mental health services, training, and research. To facilitate such collaboration, this study tested the 8-syndrome structure of the Child Behavior Checklist (CBCL) in 30 societies. Parents' CBCL ratings of 58,051 6- to 18-year-olds were subjected to confirmatory factor analyses,…

  1. Structural Changes in the Somatosensory System Correlate with Tic Severity in Gilles de la Tourette Syndrome

    Science.gov (United States)

    Thomalla, Gotz; Siebner, Hartwig R.; Jonas, Melanie; Baumer, Tobias; Biermann-Ruben, Katja; Hummel, Friedhelm; Gerloff, Christian; Muller-Vahl, Kirsten; Schnitzler, Alfons; Orth, Michael; Munchau, Alexander

    2009-01-01

    Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. Previous structural MRI studies have identified regional abnormalities in grey matter, especially in the basal ganglia. These findings are consistent with the assumption of alterations in cortico-striato-thalamo-cortical circuits and…

  2. Factor Structure of the Children's Behavior Questionnaire in Children with Williams Syndrome

    Science.gov (United States)

    Leyfer, Ovsanna; John, Angela E.; Woodruff-Borden, Janet; Mervis, Carolyn B.

    2012-01-01

    To examine the factor structure of temperament in 5-10-year-olds with Williams syndrome, an exploratory factor analysis was conducted on the responses of parents of 192 children on the children's behavior questionnaire. Four factors were identified. Two corresponded to factors reported for typically developing children: effortful control and…

  3. Detection and typing of highly pathogenic porcine reproductive and respiratory syndrome virus by multiplex real-time rt-PCR.

    Directory of Open Access Journals (Sweden)

    Kerstin Wernike

    Full Text Available Porcine reproductive and respiratory syndrome (PRRS causes economic losses in the pig industry worldwide, and PRRS viruses (PRRSV are classified into the two distinct genotypes "North American (NA, type 2" and "European (EU, type 1". In 2006, a highly pathogenic NA strain of PRRSV (HP-PRRSV, characterized by high fever as well as high morbidity and mortality, emerged in swine farms in China. Therefore, a real-time reverse transcription polymerase chain reaction (RT-qPCR assay specific for HP-PRRSV was developed and combined with type 1- and type 2-specific RT-qPCR systems. Furthermore, an internal control, based on a heterologous RNA, was successfully introduced. This final multiplex PRRSV RT-qPCR, detecting and typing PRRSV, had an analytical sensitivity of less than 200 copies per µl for the type 1-assay and 20 copies per µl for the type 2- and HP assays and a high diagnostic sensitivity. A panel of reference strains and field isolates was reliably detected and samples from an animal trial with a Chinese HP-PRRS strain were used for test validation. The new multiplex PRRSV RT-qPCR system allows for the first time the highly sensitive detection and rapid differentiation of PRRSV of both genotypes as well as the direct detection of HP-PRRSV.

  4. Simple and rapid detection of the porcine reproductive and respiratory syndrome virus from pig whole blood using filter paper.

    Science.gov (United States)

    Inoue, Ryo; Tsukahara, Takamitsu; Sunaba, Chinatsu; Itoh, Mitsugi; Ushida, Kazunari

    2007-04-01

    The combination of Flinders Technology Associates filter papers (FTA cards) and real-time PCR was examined to establish a simple and rapid technique for the detection of porcine reproductive and respiratory syndrome virus (PRRSV) from whole pig blood. A modified live PRRS vaccine was diluted with either sterilised saline or pig whole blood, and the suspensions were applied onto the FTA cards. The real-time RT-PCR detection of PRRSV was performed directly with the samples applied to the FTA card without the RNA extraction step. Six whole blood samples from at random selected piglets in the PRRSV infected farm were also assayed in this study. The expected PCR product was successfully amplified from either saline diluted or pig whole blood diluted vaccine. The same PCR ampliocon was detected from all blood samples assayed in this study. This study suggested that the combination of an FTA card and real-time PCR is a rapid and easy technique for the detection of PRRSV. This technique can remarkably shorten the time required for PRRSV detection from whole blood and makes the procedure much easier.

  5. Behavioral surveillance survey regarding human immunodeficiency virus/acquired immunodeficiency syndrome among high school and junior college students

    Directory of Open Access Journals (Sweden)

    Bhosale S

    2010-01-01

    Full Text Available Background and Aims: It is necessary to know the baseline knowledge, attitude, and practices about human immunodeficiency virus/acquired immunodeficiency syndrome among young people and the changes in these with intervention to guide prevention efforts. Methods: A cross-sectional pre- and post-survey with health education as a method of intervention was carried out in four different randomly selected schools and junior colleges among the Class IX-XII students of both sex. Instrument developed by the World Health Organization (WHO/UNAIDS in their best practice recommendations was used for data collection. Results: Knowledge about all correct methods was present in 61.23% of the respondents. Knowledge of at least two methods of prevention was present in 70.31% of the respondents. Misconceptions about prevention were that good diet (33.42%, avoiding mosquito bite (49.71% and avoiding public toilets (65.14% could help in the prevention. With intervention, there was an improvement in the knowledge. However, the proportion of students with misconceptions did not come down. Correct knowledge about two methods of prevention also did not reach the WHO recommendation of 90%. Conclusion: It is very difficult to change the attitude and practices by a single health educational intervention and an ongoing behavior change communication is recommended.

  6. Novel approaches for Spatial and Molecular Surveillance of Porcine Reproductive and Respiratory Syndrome Virus (PRRSv) in the United States.

    Science.gov (United States)

    Alkhamis, Moh A; Arruda, Andreia G; Morrison, Robert B; Perez, Andres M

    2017-06-28

    The US swine industry has been impaired over the last 25 years by the far-reaching financial losses caused by the porcine reproductive and respiratory syndrome (PRRS). Here, we explored the relations between the spatial risk of PRRS outbreaks and its phylodynamic history in the U.S during 1998-2016 using ORF5 sequences collected from swine farms in the Midwest region. We used maximum entropy and Bayesian phylodynamic models to generate risk maps for PRRS outbreaks and reconstructed the evolutionary history of three selected phylogenetic clades (A, B and C). High-risk areas for PRRS were best-predicted by pig density and climate seasonality and included Minnesota, Iowa and South Dakota. Phylodynamic models demonstrated that the geographical spread of the three clades followed a heterogeneous spatial diffusion process. Furthermore, PRRS viruses were characterized by typical seasonality in their population size. However, endemic strains were characterized by a substantially slower population growth and evolutionary rates, as well as smaller spatial dispersal rates when compared to emerging strains. We demonstrated the prospects of combining inferences derived from two unique analytical methods to inform decisions related to risk-based interventions of an important pathogen affecting one of the largest food animal industries in the world.

  7. Dobrava virus carried by the yellow-necked field mouse Apodemus flavicollis, causing hemorrhagic fever with renal syndrome in Romania.

    Science.gov (United States)

    Panculescu-Gatej, Raluca Ioana; Sirbu, Anca; Dinu, Sorin; Waldstrom, Maria; Heyman, Paul; Murariu, Dimitru; Petrescu, Angela; Szmal, Camelia; Oprisan, Gabriela; Lundkvist, Ake; Ceianu, Cornelia S

    2014-05-01

    Hemorrhagic fever with renal syndrome (HFRS) has been confirmed by serological methods during recent years in Romania. In the present study, focus-reduction neutralization tests (FRNT) confirmed Dobrava hantavirus (DOBV) as the causative agent in some HFRS cases, but could not distinguish between DOBV and Saaremaa virus (SAAV) infections in other cases. DOBV was detected by a DOBV-specific TaqMan assay in sera of nine patients out of 22 tested. Partial sequences of the M genomic segment of DOBV were obtained from sera of three patients and revealed the circulation of two DOBV lineages in Romania. Investigation of rodents trapped in Romania found three DOBV-positive Apodemus flavicollis out of 83 rodents tested. Two different DOBV lineages were also detected in A. flavicollis as determined from partial sequences of the M and S genomic segments. Sequences of DOBV in A. flavicollis were either identical or closely related to the sequences obtained from the HFRS patients. The DOBV strains circulating in Romania clustered in two monophyletic groups, together with strains from Slovenia and the north of Greece. This is the first evidence for the circulation of DOBV in wild rodents and for a DOBV etiology of HFRS in Romania.

  8. New clinical and histological patterns of acute disseminated histoplasmosis in human immunodeficiency virus-positive patients with acquired immunodeficiency syndrome.

    Science.gov (United States)

    Ollague Sierra, Jose E; Ollague Torres, Jose M

    2013-04-01

    Histoplasmosis has attained increasing relevance in the past 3 decades because of the appearance of the human immunodeficiency virus (HIV). In most immunocompetent persons, the infection is asymptomatic or can produce a respiratory condition with symptoms and radiological images similar to those observed in pulmonary tuberculosis; in non-HIV+ immunocompromised patients, it can cause respiratory symptoms or evolve into a disseminated infection. The same can occur in acquired immunodeficiency syndrome (AIDS) patients. We have observed a series of HIV+ patients with AIDS who presented with cutaneous histoplasmosis and in whom the clinical and histopathological features were highly unusual, including variable mucocutaneous lesions that were difficult to diagnose clinically. These patients displayed unusual, previously undescribed, histological patterns, including lichenoid pattern, nodular pseudomyxoid pattern, pyogenic granuloma-like pattern, perifollicular pattern, and superficial (S), mid (M), and deep perivascular dermatitis; and more commonly encountered patterns, such as histiocytic lobular panniculitis and focal nodular dermatitis. The novel histopathological patterns of cutaneous involvement by histoplasmosis seen in these patients resembled other common inflammatory and infectious conditions and required a high level of suspicion and the application of special stains for organisms for confirmation. These new, clinical, and histological findings do not seem to be commonly encountered in HIV- patients infected with the fungus but seem to be displayed most prominently in HIV+ patients with AIDS.

  9. Graphene oxide based fluorescence resonance energy transfer and loop-mediated isothermal amplification for white spot syndrome virus detection.

    Science.gov (United States)

    Waiwijit, U; Phokaratkul, D; Kampeera, J; Lomas, T; Wisitsoraat, A; Kiatpathomchai, W; Tuantranont, A

    2015-10-20

    Graphene oxide (GO) is attractived for biological or medical applications due to its unique electrical, physical, optical and biological properties. In particular, GO can adsorb DNA via π-π stacking or non-covalent interactions, leading to fluorescence quenching phenomenon applicable for bio-molecular detection. In this work, a new method for white spot syndrome virus (WSSV)-DNA detection is developed based on loop-mediated isothermal amplification (LAMP) combined with fluorescence resonance energy transfer (FRET) between GO and fluorescein isothiocyanate-labeled probe (FITC-probe). The fluorescence quenching efficiency of FITC-probe was found to increase with increasing GO concentration and reached 98.7% at a GO concentration of 50 μg/ml. The fluorescence intensity of FITC-probe was recovered after hybridization with WSSV LAMP product with an optimal hybridization time of 10 min and increased accordingly with increasing amount of LAMP products. The detection limit was estimated to be as low as 10 copies of WSSV plasmid DNA or 0.6 fg of the total DNA extracted from shrimp infected with WSSV. In addition, no cross reaction was observed with other common shrimp viral pathogens. Therefore, the GO-FRET-LAMP technique is promising for fast, sensitive and specific detection of DNAs. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Prevalence of severe fever with thrombocytopenia syndrome virus in black goats (Capra hircus coreanae) in the Republic of Korea.

    Science.gov (United States)

    Kang, Jun-Gu; Cho, Yoon-Kyoung; Jo, Yong-Sun; Chae, Jeong-Byoung; Oh, Sung-Suck; Kim, Kye-Hyung; Ko, Mee-Kyung; Yi, Jongyoun; Choi, Kyoung-Seong; Yu, Do-Hyeon; Kim, Hyeon-Cheol; Park, Jinho; Park, Bae-Keun; Choi, Chang-Yong; Jung, Young-Hun; Chae, Joon-Seok

    2018-04-26

    Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen in China, Japan, and the Republic of Korea (ROK). The aim of this study was to investigate the prevalence of SFTSV antigens and anti-SFTSV antibodies in black goats (Capra hircus coreanae) throughout the ROK. Sera were collected from 737 black goats in nine provinces in the ROK. Eighteen of 737 (2.4%) goat sera were positive for SFTSV on one-step reverse transcription nested polymerase chain reaction. The amplified 346-bp S segments of SFTSV sequences were classified into three genotypes (BG1, BG2, and BG3), and were included in the Japanese clade rather than the Chinese clade, based on phylogenetic analysis. Forty-three of 624 (6.9%) serum samples were seropositive for anti-SFTSV antibodies on enzyme-linked immunosorbent assay analysis. This study is the first to examine the molecular prevalence of SFTSV in goats and the first to perform serological detection of anti-SFTSV antibodies in livestock in the ROK. Moreover, the results indicate that SFTSV is widely distributed in goats and that additional monitoring for SFTSV is needed in livestock in the ROK. Copyright © 2018 Elsevier GmbH. All rights reserved.

  11. Depression among people living with human immunodeficiency virus infection/acquired immunodeficiency syndrome in Benin City, Nigeria: a comparative study.

    Science.gov (United States)

    Chikezie, U E; Otakpor, A N; Kuteyi, O B; James, B O

    2013-01-01

    Depression is a common co-morbidity among persons living with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) (PLWHAs). It is associated with poor treatment adherence and higher mortality rates. Few reports have, however, emanated from developing countries where socioeconomic factors may confound this association. We conducted a cross-sectional comparative study of PLWHAs and apparently healthy staff of three LGA's. The depression module of the Schedule for the Clinical Assessment in Neuropsychiatry (SCAN) and the Beck Depression Inventory (BDI) was used to diagnose depression and depression symptom severity, respectively. Depression was commonly co-morbid among individuals with HIV/AIDS. It was five times more common in PLWHAs than in apparently healthy populations (29.3% vs. 7.3%, OR: 5.25, 95% CI: 2.50-11.76). A similar trend was observed for depression symptom severity. Among PLWHAs, depression was significantly more likely among females (OR: 7.91, 95% CI: 1.83-71.00, P 3 years (OR: 7.90, P risk. Depression was commonly co-morbid among PLWHAs studied. Clinicians should be aware of risk factors for depression among PLWHAs in order to improve treatment outcomes.

  12. White spot syndrome virus (WSSV) genome stability maintained over six passages through three different penaeid shrimp species.

    Science.gov (United States)

    Sindhupriya, M; Saravanan, P; Otta, S K; Amarnath, C Bala; Arulraj, R; Bhuvaneswari, T; Praveena, P Ezhil; Jithendran, K P; Ponniah, A G

    2014-08-21

    White spot syndrome virus (WSSV) replicates rapidly, can be extremely pathogenic and is a common cause of mass mortality in cultured shrimp. Variable number tandem repeat (VNTR) sequences present in the open reading frame (ORF)94, ORF125 and ORF75 regions of the WSSV genome have been used widely as genetic markers in epidemiological studies. However, reports that VNTRs might evolve rapidly following even a single transmission through penaeid shrimp or other crustacean hosts have created confusion as to how VNTR data is interpreted. To examine VNTR stability again, 2 WSSV strains (PmTN4RU and LvAP11RU) with differing ORF94 tandem repeat numbers and slight differences in apparent virulence were passaged sequentially 6 times through black tiger shrimp Penaeus monodon, Indian white shrimp Feneropenaeus indicus or Pacific white leg shrimp Litopenaeus vannamei. PCR analyses to genotype the ORF94, ORF125 and ORF75 VNTRs did not identify any differences from either of the 2 parental WSSV strains after multiple passages through any of the shrimp species. These data were confirmed by sequence analysis and indicate that the stability of the genome regions containing these VNTRs is quite high at least for the WSSV strains, hosts and number of passages examined and that the VNTR sequences thus represent useful genetic markers for studying WSSV epidemiology.

  13. Envelope Proteins of White Spot Syndrome Virus (WSSV Interact with Litopenaeus vannamei Peritrophin-Like Protein (LvPT.

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    Shijun Xie

    Full Text Available White spot syndrome virus (WSSV is a major pathogen in shrimp cultures. The interactions between viral proteins and their receptors on the surface of cells in a frontier target tissue are crucial for triggering an infection. In this study, a yeast two-hybrid (Y2H library was constructed using cDNA obtained from the stomach and gut of Litopenaeus vannamei, to ascertain the role of envelope proteins in WSSV infection. For this purpose, VP37 was used as the bait in the Y2H library screening. Forty positive clones were detected after screening. The positive clones were analyzed and discriminated, and two clones belonging to the peritrophin family were subsequently confirmed as genuine positive clones. Sequence analysis revealed that both clones could be considered as the same gene, LV-peritrophin (LvPT. Co-immunoprecipitation confirmed the interaction between LvPT and VP37. Further studies in the Y2H system revealed that LvPT could also interact with other WSSV envelope proteins such as VP32, VP38A, VP39B, and VP41A. The distribution of LvPT in tissues revealed that LvPT was mainly expressed in the stomach than in other tissues. In addition, LvPT was found to be a secretory protein, and its chitin-binding ability was also confirmed.

  14. Increased rates of Guillain-Barré syndrome associated with Zika virus outbreak in the Salvador metropolitan area, Brazil.

    Directory of Open Access Journals (Sweden)

    Ashley R Styczynski

    2017-08-01

    Full Text Available In mid-2015, Salvador, Brazil, reported an outbreak of Guillain-Barré syndrome (GBS, coinciding with the introduction and spread of Zika virus (ZIKV. We found that GBS incidence during April-July 2015 among those ≥12 years of age was 5.6 cases/100,000 population/year and increased markedly with increasing age to 14.7 among those ≥60 years of age. We conducted interviews with 41 case-patients and 85 neighborhood controls and found no differences in demographics or exposures prior to GBS-symptom onset. A higher proportion of case-patients (83% compared to controls (21% reported an antecedent illness (OR 18.1, CI 6.9-47.5, most commonly characterized by rash, headache, fever, and myalgias, within a median of 8 days prior to GBS onset. Our investigation confirmed an outbreak of GBS, particularly in older adults, that was strongly associated with Zika-like illness and geo-temporally associated with ZIKV transmission, suggesting that ZIKV may result in severe neurologic complications.

  15. Increased rates of Guillain-Barré syndrome associated with Zika virus outbreak in the Salvador metropolitan area, Brazil.

    Science.gov (United States)

    Styczynski, Ashley R; Malta, Juliane M A S; Krow-Lucal, Elisabeth R; Percio, Jadher; Nóbrega, Martha E; Vargas, Alexander; Lanzieri, Tatiana M; Leite, Priscila L; Staples, J Erin; Fischer, Marc X; Powers, Ann M; Chang, Gwong-Jen J; Burns, P L; Borland, Erin M; Ledermann, Jeremy P; Mossel, Eric C; Schonberger, Lawrence B; Belay, Ermias B; Salinas, Jorge L; Badaro, Roberto D; Sejvar, James J; Coelho, Giovanini E

    2017-08-01

    In mid-2015, Salvador, Brazil, reported an outbreak of Guillain-Barré syndrome (GBS), coinciding with the introduction and spread of Zika virus (ZIKV). We found that GBS incidence during April-July 2015 among those ≥12 years of age was 5.6 cases/100,000 population/year and increased markedly with increasing age to 14.7 among those ≥60 years of age. We conducted interviews with 41 case-patients and 85 neighborhood controls and found no differences in demographics or exposures prior to GBS-symptom onset. A higher proportion of case-patients (83%) compared to controls (21%) reported an antecedent illness (OR 18.1, CI 6.9-47.5), most commonly characterized by rash, headache, fever, and myalgias, within a median of 8 days prior to GBS onset. Our investigation confirmed an outbreak of GBS, particularly in older adults, that was strongly associated with Zika-like illness and geo-temporally associated with ZIKV transmission, suggesting that ZIKV may result in severe neurologic complications.

  16. Interaction between single-dose Mycoplasma hyopneumoniae and porcine reproductive and respiratory syndrome virus vaccines on dually infected pigs.

    Science.gov (United States)

    Park, Su-Jin; Seo, Hwi Won; Park, Changhoon; Chae, Chanhee

    2014-06-01

    The objective of this study was to determine the effects of Mycoplasma hyopneumoniae and/or porcine reproductive and respiratory syndrome virus (PRRSV) vaccination on dually infected pigs. In total, 72 pigs were randomly divided into nine groups (eight pigs per group), as follows: five vaccinated and challenged groups, three non-vaccinated and challenged groups, and a negative control group. Single-dose vaccination against M. hyopneumoniae alone decreased the levels of PRRSV viremia and PRRSV-induced pulmonary lesions, whereas single-dose vaccination against PRRSV alone did not decrease nasal shedding of M. hyopneumoniae and mycoplasma-induced pulmonary lesions in the dually infected pigs. The M. hyopneumoniae challenge impaired the protective cell-mediated immunity induced by the PRRSV vaccine, whereas the PRRSV challenge did not impair the protective cell-mediated immunity induced by the M. hyopneumoniae vaccine. The present study provides swine practitioners and producers with efficient vaccination regimes; vaccination against M. hyopneumoniae is the first step in protecting pigs against co-infection with M. hyopneumoniae and PRRSV. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Efficacy of combined vaccination against Mycoplasma hyopneumoniae and porcine reproductive and respiratory syndrome virus in dually infected pigs.

    Science.gov (United States)

    Bourry, Olivier; Fablet, Christelle; Simon, Gaëlle; Marois-Créhan, Corinne

    2015-11-18

    Porcine respiratory disease complex (PRDC) is one of the main causes of economic losses for swine producers. This complex is due to a combination of different pathogens and their interactions. Two major pathogens involved in PRDC are Mycoplasma hyopneumoniae (Mhp) and porcine reproductive and respiratory syndrome virus (PRRSV). The objectives of this study were (i) to develop an experimental model of dual Mhp/PRRSV infection in SPF pigs with European strains of Mhp and PRRSV and (ii) to assess and compare the effects of single Mhp, single PRRSV or combined Mhp/PRRSV vaccination against this dual infection. Pigs dually infected with Mhp and PRRSV showed a combination of symptoms characteristic of each pathogen but no significant exacerbation of pathogenicity. Thus, the co-infected pigs displayed coughing and pneumonia typical of Mhp infection in addition to PRRSV-related hyperthermia and decrease in average daily gain (ADG). Hyperthermia was reduced in PRRSV vaccinated animals (single or combined vaccination), whereas ADG was restored in Mhp/PRRSV vaccinated pigs only. Regarding respiratory symptoms and lung lesions, no vaccine decreased coughing. However, all vaccines reduced the pneumonia score but more so in animals receiving the Mhp vaccine, whether single or combined. This vaccine also decreased the Mhp load in the respiratory tract. In conclusion, combined vaccination against both Mhp and PRRSV efficiently pooled the efficacy of each single PRRSV and Mhp vaccination and could be an interesting tool to control PRDC in European swine production. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Novel Insights into Antiviral Gene Regulation of Red Swamp Crayfish, Procambarus clarkii, Infected with White Spot Syndrome Virus

    Directory of Open Access Journals (Sweden)

    Shaokui Yi

    2017-11-01

    Full Text Available White spot syndrome virus (WSSV, one of the major pathogens of Procambarus clarkii, has caused severe disruption to the aquaculture industry of P. clarkii in China. To reveal the gene regulatory mechanisms underlying WSSV infection, a comparative transcriptome analysis was performed among WSSV-infected susceptible individuals (GS, viral resistant individuals (GR, and a non-infected control group (GC. A total of 61,349 unigenes were assembled from nine libraries. Subsequently, 515 and 1033 unigenes exhibited significant differential expression in sensitive and resistant crayfish individuals compared to the control group (GC. Many differentially expressed genes (e.g., C-type lectin 4, Peroxinectin, Prophenoloxidase, and Serine/threonine-protein kinase observed in GR and GS play critical roles in pathogen recognition and viral defense reactions after WSSV infection. Importantly, the glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate pathway was identified to play critical roles in defense to WSSV infection for resistant crayfish individuals by upregulating the chondroitin sulfate related genes for the synthesis of WSSV-sensitive, functional chondroitin sulfate chains containing E units. Numerous genes and the key pathways identified between resistant and susceptible P. clarkii individuals provide valuable insights regarding antiviral response mechanisms of decapoda species and may help to improve the selective breeding of P. clarkii WSSV-resistance.

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

    Science.gov (United States)

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

    2016-09-01

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

  20. Body temperature and motion: Evaluation of an online monitoring system in pigs challenged with Porcine Reproductive & Respiratory Syndrome Virus.

    Science.gov (United States)

    Süli, Tamás; Halas, Máté; Benyeda, Zsófia; Boda, Réka; Belák, Sándor; Martínez-Avilés, Marta; Fernández-Carrión, Eduardo; Sánchez-Vizcaíno, José Manuel

    2017-10-01

    Highly contagious and emerging diseases cause significant losses in the pig producing industry worldwide. Rapid and exact acquisition of real-time data, like body temperature and animal movement from the production facilities would enable early disease detection and facilitate adequate response. In this study, carried out within the European Union research project RAPIDIA FIELD, we tested an online monitoring system on pigs experimentally infected with the East European subtype 3 Porcine Reproductive & Respiratory Syndrome Virus (PRRSV) strain Lena. We linked data from different body temperature measurement methods and the real-time movement of the pigs. The results showed a negative correlation between body temperature and movement of the animals. The correlation was similar with both body temperature obtaining methods, rectal and thermal sensing microchip, suggesting some advantages of body temperature measurement with transponders compared with invasive and laborious rectal measuring. We also found a significant difference between motion values before and after the challenge with a virulent PRRSV strain. The decrease in motion values was noticeable before any clinical sign was recorded. Based on our results the online monitoring system could represent a practical tool in registering early warning signs of health status alterations, both in experimental and commercial production settings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Insights from the structure of a smallpox virus topoisomerase-DNA transition state mimic

    Science.gov (United States)

    Perry, Kay; Hwang, Young; Bushman, Frederic D.; Van Duyne, Gregory D.

    2010-01-01

    Summary Poxviruses encode their own type IB topoisomerases (TopIBs) which release superhelical tension generated by replication and transcription of their genomes. To investigate the reaction catalyzed viral TopIBs, we have determined the structure of a variola virus topoisomerase-DNA complex trapped as a vanadate transition state mimic. The structure reveals how the viral TopIB enzymes are likely to position the DNA duplex for ligation following relaxation of supercoils and identifies the sources of friction observed in single molecule experiments that argue against free rotation. The structure also identifies a conformational change in the leaving group sugar that must occur prior to cleavage and reveals a mechanism for promoting ligation following relaxation of supercoils that involves a novel Asp-minor groove interaction. Overall, the new structural data support a common catalytic mechanism for the TopIB superfamily but indicate distinct methods for controlling duplex rotation in the small vs. large enzyme subfamilies. PMID:20152159

  2. Dengue Virus Non-structural Protein 1 Modulates Infectious Particle Production via Interaction with the Structural Proteins.

    Directory of Open Access Journals (Sweden)

    Pietro Scaturro

    Full Text Available Non-structural protein 1 (NS1 is one of the most enigmatic proteins of the Dengue virus (DENV, playing distinct functions in immune evasion, pathogenesis and viral replication. The recently reported crystal structure of DENV NS1 revealed its peculiar three-dimensional fold; however, detailed information on NS1 function at different steps of the viral replication cycle is still missing. By using the recently reported crystal structure, as well as amino acid sequence conservation, as a guide for a comprehensive site-directed mutagenesis study, we discovered that in addition to being essential for RNA replication, DENV NS1 is also critically required for the production of infectious virus particles. Taking advantage of a trans-complementation approach based on fully functional epitope-tagged NS1 variants, we identified previously unreported interactions between NS1 and the structural proteins Envelope (E and precursor Membrane (prM. Interestingly, coimmunoprecipitation revealed an additional association with capsid, arguing that NS1 interacts via the structural glycoproteins with DENV particles. Results obtained with mutations residing either in the NS1 Wing domain or in the β-ladder domain suggest that NS1 might have two distinct functions in the assembly of DENV particles. By using a trans-complementation approach with a C-terminally KDEL-tagged ER-resident NS1, we demonstrate that the secretion of NS1 is dispensable for both RNA replication and infectious particle production. In conclusion, our results provide an extensive genetic map of NS1 determinants essential for viral RNA replication and identify a novel role of NS1 in virion production that is mediated via interaction with the structural proteins. These studies extend the list of NS1 functions and argue for a central role in coordinating replication and assembly/release of infectious DENV particles.

  3. Structure of the parainfluenza virus 5 (PIV5 hemagglutinin-neuraminidase (HN ectodomain.

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    Brett D Welch

    Full Text Available Paramyxoviruses cause a wide variety of human and animal diseases. They infect host cells using the coordinated action of two surface glycoproteins, the receptor binding protein (HN, H, or G and the fusion protein (F. HN binds sialic acid on host cells (hemagglutinin activity and hydrolyzes these receptors during viral egress (neuraminidase activity, NA. Additionally, receptor binding is thought to induce a conformational change in HN that subsequently triggers major refolding in homotypic F, resulting in fusion of virus and target cell membranes. HN is an oligomeric type II transmembrane protein with a short cytoplasmic domain and a large ectodomain comprising a long helical stalk and large globular head domain containing the enzymatic functions (NA domain. Extensive biochemical characterization has revealed that HN-stalk residues determine F specificity and activation. However, the F/HN interaction and the mechanisms whereby receptor binding regulates F activation are poorly defined. Recently, a structure of Newcastle disease virus (NDV HN ectodomain revealed the heads (NA domains in a "4-heads-down" conformation whereby two of the heads form a symmetrical interaction with two sides of the stalk. The interface includes stalk residues implicated in triggering F, and the heads sterically shield these residues from interaction with F (at least on two sides. Here we report the x-ray crystal structure of parainfluenza virus 5 (PIV5 HN ectodomain in a "2-heads-up/2-heads-down" conformation where two heads (covalent dimers are in the "down position," forming a similar interface as observed in the NDV HN ectodomain structure, and two heads are in an "up position." The structure supports a model in which the heads of HN transition from down to up upon receptor binding thereby releasing steric constraints and facilitating the interaction between critical HN-stalk residues and F.

  4. Multiscale molecular dynamics simulation approaches to the structure and dynamics of viruses.

    Science.gov (United States)

    Huber, Roland G; Marzinek, Jan K; Holdbrook, Daniel A; Bond, Peter J

    2017-09-01

    Viral pathogens are a significant source of human morbidity and mortality, and have a major impact on societies and economies around the world. One of the challenges inherent in targeting these pathogens with drugs is the tight integration of the viral life cycle with the host's cellular machinery. However, the reliance of the virus on the host cell replication machinery is also an opportunity for therapeutic targeting, as successful entry- and exit-inhibitors have demonstrated. An understanding of the extracellular and intracellular structure and dynamics of the virion - as well as of the entry and exit pathways in host and vector cells - is therefore crucial to the advancement of novel antivirals. In recent years, advances in computing architecture and algorithms have begun to allow us to use simulations to study the structure and dynamics of viral ultrastructures at various stages of their life cycle in atomistic or near-atomistic detail. In this review, we outline specific challenges and solutions that have emerged to allow for structurally detailed modelling of viruses in silico. We focus on the history and state of the art of atomistic and coarse-grained approaches to simulate the dynamics of the large, macromolecular structures associated with viral infection, and on their usefulness in explaining and expanding upon experimental data. We discuss the types of interactions that need to be modeled to describe major components of the virus particle and advances in modelling techniques that allow for the treatment of these systems, highlighting recent key simulation studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Identification and characterization of a novel non-structural protein of bluetongue virus.

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    Maxime Ratinier

    2011-12-01

    Full Text Available Bluetongue virus (BTV is the causative agent of a major disease of livestock (bluetongue. For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4 encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77-79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell.

  6. Molecular Diagnostics of Hemorrhagic Fever with Renal Syndrome during a Dobrava Virus Infection Outbreak in the European Part of Russia ▿

    Science.gov (United States)

    Dzagurova, Tamara K.; Klempa, Boris; Tkachenko, Evgeniy A.; Slyusareva, Galina P.; Morozov, Vyacheslav G.; Auste, Brita; Kruger, Detlev H.

    2009-01-01

    A large outbreak of hemorrhagic fever with renal syndrome (HFRS) occurred in the winter of 2006-2007 in a region southeast of Moscow in Central European Russia. Of the 422 patients with HFRS investigated in this study, 58 patients were found to be infected by Puumala virus, whereas as many as 364 were infected by Dobrava-Belgrade virus (DOBV). Early serum samples from 10 DOBV-infected patients were used for nucleic acid amplification, which was successful for 5 patients. Molecular analyses demonstrated that the causative hantavirus belongs to the DOBV-Aa genetic lineage, which is carried by the striped field mouse (Apodemus agrarius) as the natural reservoir host. Neutralization assays with convalescent-phase sera from these patients confirmed infection by DOBV-Aa; related viruses, such as the Dobrava-Slovenia virus (DOBV-Af) and the Dobrava-Sochi virus (DOBV-Ap), were neutralized at lower efficiencies. The clinical courses of the 205 patients enrolled in the study were found to be mostly mild to moderate; however, an unexpectedly high fraction (27%) of patients exhibited severe illness. One patient died from kidney failure and showed symptoms of generalized subcutaneous hemorrhage. The results provide molecular, serodiagnostic, and clinical evidence that DOBV-Aa is a common pathogen in East Europe that causes large outbreaks of HFRS. PMID:19828747

  7. Interferon alpha inhibits replication of a live-attenuated porcine reproductive and respiratory syndrome virus vaccine preventing development of an adaptive immune response in swine.

    Science.gov (United States)

    Brockmeier, Susan L; Loving, Crystal L; Eberle, Kirsten C; Hau, Samantha J; Buckley, Alexandra; Van Geelen, Albert; Montiel, Nestor A; Nicholson, Tracy; Lager, Kelly M

    2017-12-01

    Type I interferons, such as interferon alpha (IFN-α), contribute to innate antiviral immunity by promoting production of antiviral mediators and are also involved in promoting an adaptive immune response. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating and costly viruses to the swine industry world-wide and has been shown to induce a meager IFN-α response. Previously we administered porcine IFN-α using a replication-defective adenovirus vector (Ad5-IFN-α) at the time of challenge with virulent PRRSV and demonstrated an increase in the number of virus-specific IFNγ secreting cells, indicating that the presence of IFN-α at the time of infection can alter the adaptive immune responses to PRRSV. In the current experiment, we explored the use of IFN-α as an adjuvant administered with live-attenuated PRRSV vaccine as a method to enhance immune response to the vaccine. Unlike the previous studies with fully virulent virus, one injection of the Ad5-IFN-α abolished replication of the vaccine virus and as a result there was no detectible adaptive immune response. Although IFN-α did not have the desired adjuvant effect, the results further highlight the use of IFN-α as a treatment for PRRSV infection. Published by Elsevier B.V.

  8. Cholecystitis and nephrotic syndrome complicating Epstein-Barr virus primary infection.

    Science.gov (United States)

    Rodà, Diana; Huici, Malka; Ricart, Sílvia; Vila, Jordi; Fortuny, Clàudia; Alsina, Laia

    2017-02-01

    Epstein-Barr virus (EBV) infection results in a spectrum of clinical manifestations. The host immune response to EBV plays a key role in the extent and degree of clinical features, which in children under 4 years of age are usually mild, non-specific and self-limiting. A 2-year-old boy in whom no known immune disorder could be found presented with acute acalculous cholecystitis, renal dysfunction with massive proteinuria, ascites, pleural effusion, minimal peripheral oedema and a severe systemic inflammatory response. Improvement occurred after initiation of corticosteroids and antiviral treatment with gancyclovir. In severely symptomatic or complicated EBV infection, a primary immunodeficiency must be suspected. If a primary immunodeficiency has been ruled out, the correct management of severe EBV infection in the immunocompetent host remains controversial.

  9. Structure-based drug discovery for combating influenza virus by targeting the PA-PB1 interaction.

    Science.gov (United States)

    Watanabe, Ken; Ishikawa, Takeshi; Otaki, Hiroki; Mizuta, Satoshi; Hamada, Tsuyoshi; Nakagaki, Takehiro; Ishibashi, Daisuke; Urata, Shuzo; Yasuda, Jiro; Tanaka, Yoshimasa; Nishida, Noriyuki

    2017-08-25

    Influenza virus infections are serious public health concerns throughout the world. The development of compounds with novel mechanisms of action is urgently required due to the emergence of viruses with resistance to the currently-approved anti-influenza viral drugs. We performed in silico screening using a structure-based drug discovery algorithm called Nagasaki University Docking Engine (NUDE), which is optimised for a GPU-based supercomputer (DEstination for Gpu Intensive MAchine; DEGIMA), by targeting influenza viral PA protein. The compounds selected by NUDE were tested for anti-influenza virus activity using a cell-based assay. The most potent compound, designated as PA-49, is a medium-sized quinolinone derivative bearing a tetrazole moiety, and it inhibited the replication of influenza virus A/WSN/33 at a half maximal inhibitory concentration of 0.47 μM. PA-49 has the ability to bind PA and its anti-influenza activity was promising against various influenza strains, including a clinical isolate of A(H1N1)pdm09 and type B viruses. The docking simulation suggested that PA-49 interrupts the PA-PB1 interface where important amino acids are mostly conserved in the virus strains tested, suggesting the strain independent utility. Because our NUDE/DEGIMA system is rapid and efficient, it may help effective drug discovery against the influenza virus and other emerging viruses.

  10. High prevalence of common respiratory viruses and no evidence of Middle East respiratory syndrome coronavirus in Hajj pilgrims returning to Ghana, 2013.

    Science.gov (United States)

    Annan, Augustina; Owusu, Michael; Marfo, Kwadwo Sarfo; Larbi, Richard; Sarpong, Francisca Naana; Adu-Sarkodie, Yaw; Amankwa, Joseph; Fiafemetsi, Samuel; Drosten, Christian; Owusu-Dabo, Ellis; Eckerle, Isabella

    2015-06-01

    The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 on the Arabian Peninsula and has caused severe respiratory disease with more than 800 laboratory-confirmed cases. The return of infected pilgrims to their home countries with a putative spread of MERS-CoV necessitates further surveillance. A cross sectional study of 839 adult African Hajj pilgrims returning to Accra in Ghana, West Africa, was conducted in 2013 to assess the prevalence of respiratory symptoms as well as of MERS-CoV, human rhinovirus (HRV), respiratory syncytial virus (RSV) and influenza A virus (FLU A) infection. Six hundred and fifty-one (77.6%) pilgrims had respiratory symptoms. Tests were positive for at least one of the viruses other than MERS-CoV in 179 (21.3%) of all pilgrims, with 22.4% detection in symptomatic vs. 17.6% detection in asymptomatic pilgrims. No MERS-CoV was detected, although common respiratory viruses were prevalent, with positive findings for HRV in 141 individuals (16.8%), RSV in 43 individuals (5.1%) and FLU A in 11 individuals (1.3%). Results were positive for more than one virus in 16 (1.9%) individuals, including 14 (1.7%) RSV/HRV co-infections and 2 (0.2%) FLU A/HRV co-infections. A total 146 (22.4%) of the symptomatic returnees tested positive for at least one respiratory virus compared with 33 (17.6%) of the asymptomatic pilgrims who had at least one detectable virus in their sample. The prevalence of viral respiratory infections among Hajj pilgrims in both symptomatic and asymptomatic subjects was high. Although it is reassuring that MERS-CoV was not detected in the tested population, there is a need for active surveillance of Hajj pilgrims. © 2015 John Wiley & Sons Ltd.

  11. Evolutionary patterns in the sequence and structure of transfer RNA: early origins of archaea and viruses.

    Directory of Open Access Journals (Sweden)

    Feng-Jie Sun

    2008-03-01

    Full Text Available Transfer RNAs (tRNAs are ancient molecules that are central to translation. Since they probably carry evolutionary signatures that were left behind when the living world diversified, we reconstructed phylogenies directly from the sequence and structure of tRNA using well-established phylogenetic methods. The trees placed tRNAs with long variable arms charging Sec, Tyr, Ser, and Leu consistently at the base of the rooted phylogenies, but failed to reveal groupings that would indicate clear evolutionary links to organismal origin or molecular functions. In order to uncover evolutionary patterns in the trees, we forced tRNAs into monophyletic groups using constraint analyses to generate timelines of organismal diversification and test competing evolutionary hypotheses. Remarkably, organismal timelines showed Archaea was the most ancestral superkingdom, followed by viruses, then superkingdoms Eukarya and Bacteria, in that order, supporting conclusions from recent phylogenomic studies of protein architecture. Strikingly, constraint analyses showed that the origin of viruses was not only ancient, but was linked to Archaea. Our findings have important implications. They support the notion that the archaeal lineage was very ancient, resulted in the first organismal divide, and predated diversification of tRNA function and specificity. Results are also consistent with the concept that viruses contributed to the development of the DNA replication machinery during the early diversification of the living world.

  12. Structure-based engineering of an icosahedral virus for nanomedicine and nanotechnology.

    Science.gov (United States)

    Steinmetz, N F; Lin, T; Lomonossoff, G P; Johnson, J E

    2009-01-01

    A quintessential tenet of nanotechnology is the self-assembly of nanometer-sized components into devices. Biological macromolecular systems such as viral particles were found to be suitable building blocks for nanotechnology for several reasons: viral capsids are extremely robust and can be produced in large quantities with ease, the particles self-assemble into monodisperse particles with a high degree of symmetry and polyvalency, they have the propensity to form arrays, and they offer programmability through genetic and chemical engineering. Here, we review the recent advances in engineering the icosahedral plant virus Cowpea mosaic virus (CPMV) for applications in nano-medicine and -technology. In the first part, we will discuss how the combined knowledge of the structure of CPMV at atomic resolution and the use of chimeric virus technology led to the generation of CPMV particles with short antigenic peptides for potential use as vaccine candidates. The second part focuses on the chemical addressability of CPMV. Strategies to chemically attach functional molecules at designed positions on the exterior surface of the viral particle are described. Biochemical conjugation methods led to the fabrication of electronically conducting CPMV particles and networks. In addition, functional proteins for targeted delivery to mammalian cells were successfully attached to CPMV. In the third part, we focus on the utilization of CPMV as a building block for the generation of 2D and 3D arrays. Overall, the potential applications of viral nanobuilding blocks are manifold and range from nanoelectronics to biomedical applications.

  13. Zika Virus: An Emergent Neuropathological Agent

    Science.gov (United States)

    White, Martyn K.; Wollebo, Hassen S.; Beckham, J. David; Tyler, Kenneth L.; Khalili, Kamel

    2016-01-01

    The emergence of Zika virus in the Americas has followed a pattern that is familiar from earlier epidemics of other viruses, where a new disease is introduced into a human population and then spreads rapidly with important public health consequences. In the case of Zika virus, an accumulating body of recent evidence implicates the virus in the etiology of serious pathologies of the human nervous system, that is, the occurrence of microcephaly in neonates and Guillain–Barré syndrome in adults. Zika virus is an arbovirus (arthropod-borne virus) and a member of the family Flaviviridae, genus Flavivirus. Zika virions are enveloped and icosahedral, and contain a nonsegmented, single-stranded, positive-sense RNA genome, which encodes 3 structural and 7 nonstructural proteins that are expressed as a single polyprotein that undergoes cleavage. Zika genomic RNA replicates in the cytoplasm of infected host cells. Zika virus was first detected in 1947 in the blood of a febrile monkey in Uganda’s Zika Forest and in crushed suspensions of the Aedes mosquito, which is one of the vectors for Zika virus. The virus remained obscure, with a few human cases confined to Africa and Asia. There are two lineages of the Zika virus, African and Asian, with the Asian strain causing outbreaks in Micronesia in 2007 and French Polynesia in 2013–2014. From here, the virus spread to Brazil with the first report of autochthonous Zika transmission in the Americas in March 2015. The rapid advance of the virus in the Americas and its likely association with microcephaly and Guillain–Barré syndrome make Zika an urgent public health concern. PMID:27464346

  14. GDF9 and BMP15 Expressions and Fine Structure Changes During Folliculogenesis in Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Meryem İlkay Karagül1

    2018-02-01

    Full Text Available Background: Polycystic ovary syndrome is the most frequently seen endocrine disorder in women of reproductive age with a prevalence of about 10%. Aims: To investigate the efficiency of growth differentiation factor 9 and bone morphogenetic protein 15 during folliculogenesis in a dehydroepiandrosterone-induced mouse Polycystic ovary syndrome model. Study Design: Animal experimentation. Methods: Mice were divided into 3 groups: control, vehicle and Polycystic ovary syndrome. Polycystic ovary syndrome model mice were developed by the injection of dehydroepiandrosterone dissolved in 0.1 mL of sesame oil. Ovarian tissues were examined for growth differentiation factor 9 and bone morphogenetic protein 15 using immunofluorescent labelling and electron microscopic examinations. Results: The immunoreactivity of growth differentiation factor 9 and bone morphogenetic protein 15 proteins decreased (p<0.05 in the Polycystic ovary syndrome group (27.73±8.43 and 24.85±7.03, respectively compared with the control group (33.72±11.22 and 31.12±11.05, respectively and vehicle group (33.95±10.75 and 29.99±10.72, respectively. Apoptotic changes were observed in granulosa cells, lipid vacuoles increased in Theca cells and thickening and irregularities were noted in the basal lamina of granulosa cells. An increased electron density in the zona pellucida in some of the multilaminar primary and secondary follicles in the Polycystic ovary syndrome model was also observed at the ultrastructural level. Conclusion: These results suggest that the decrease in the growth differentiation factor 9 and bone morphogenetic protein 15 expression initiated at the primary follicle stage effect the follicle development and zona pellucida structure and may cause subfertility or infertility in Polycystic ovary syndrome

  15. GDF9 and BMP15 Expressions and Fine Structure Changes During Folliculogenesis in Polycystic Ovary Syndrome.

    Science.gov (United States)

    Karagül, Meryem İlkay; Aktaş, Savaş; Coşkun Yılmaz, Banu; Yılmaz, Mustafa; Orekici Temel, Gülhan

    2018-01-20

    Polycystic ovary syndrome is the most frequently seen endocrine disorder in women of reproductive age with a prevalence of about 10%. To investigate the efficiency of growth differentiation factor 9 and bone morphogenetic protein 15 during folliculogenesis in a dehydroepiandrosterone-induced mouse Polycystic ovary syndrome model. Animal experimentation. Mice were divided into 3 groups: control, vehicle and Polycystic ovary syndrome. Polycystic ovary syndrome model mice were developed by the injection of dehydroepiandrosterone dissolved in 0.1 mL of sesame oil. Ovarian tissues were examined for growth differentiation factor 9 and bone morphogenetic protein 15 using immunofluorescent labelling and electron microscopic examinations. The immunoreactivity of growth differentiation factor 9 and bone morphogenetic protein 15 proteins decreased (pPolycystic ovary syndrome group (27.73±8.43 and 24.85±7.03, respectively) compared with the control group (33.72±11.22 and 31.12±11.05, respectively) and vehicle group (33.95±10.75 and 29.99±10.72, respectively). Apoptotic changes were observed in granulosa cells, lipid vacuoles increased in Theca cells and thickening and irregularities were noted in the basal lamina of granulosa cells. An increased electron density in the zona pellucida in some of the multilaminar primary and secondary follicles in the Polycystic ovary syndrome model was also observed at the ultrastructural level. These results suggest that the decrease in the growth differentiation factor 9 and bone morphogenetic protein 15 expression initiated at the primary follicle stage effect the follicle development and zona pellucida structure and may cause subfertility or infertility in Polycystic ovary syndrome.

  16. Structures of foot and mouth disease virus pentamers: Insight into capsid dissociation and unexpected pentamer reassociation.

    Directory of Open Access Journals (Sweden)

    Nayab Malik

    2017-09-01

    Full Text Available Foot-and-mouth disease virus (FMDV belongs to the Aphthovirus genus of the Picornaviridae, a family of small, icosahedral, non-enveloped, single-stranded RNA viruses. It is a highly infectious pathogen and is one of the biggest hindrances to the international trade of animals and animal products. FMDV capsids (which are unstable below pH6.5 release their genome into the host cell from an acidic compartment, such as that of an endosome, and in the process dissociate into pentamers. Whilst other members of the family (enteroviruses have been visualized to form an expanded intermediate capsid with holes from which inner capsid proteins (VP4, N-termini (VP1 and RNA can be released, there has been no visualization of any such state for an aphthovirus, instead the capsid appears to simply dissociate into pentamers. Here we present the 8-Å resolution structure of isolated dissociated pentamers of FMDV, lacking VP4. We also found these pentamers to re-associate into a rigid, icosahedrally symmetric assembly, which enabled their structure to be solved at higher resolution (5.2 Å. In this assembly, the pentamers unexpectedly associate 'inside out', but still with their exposed hydrophobic edges buried. Stabilizing interactions occur between the HI loop of VP2 and its symmetry related partners at the icosahedral 3-fold axes, and between the BC and EF loops of VP3 with the VP2 βB-strand and the CD loop at the 2-fold axes. A relatively extensive but subtle structural rearrangement towards the periphery of the dissociated pentamer compared to that in the mature virus provides insight into the mechanism of dissociation of FMDV and the marked difference in antigenicity.

  17. Sulfolobus Turreted Icosahedral Virus c92 Protein Responsible for the Formation of Pyramid-Like Cellular Lysis Structures

    DEFF Research Database (Denmark)

    Snyder, Jamie C; Brumfield, Susan K; Peng, Nan

    2011-01-01

    Host cells infected by Sulfolobus turreted icosahedral virus (STIV) have been shown to produce unusual pyramid-like structures on the cell surface. These structures represent a virus-induced lysis mechanism that is present in Archaea and appears to be distinct from the holin/endolysin system desc...... disruption of c92 within STIV demonstrates that c92 is an essential protein for virus replication. Immunolocalization of c92 shows that the protein is localized to the cellular membranes forming the pyramid-like structures.......Host cells infected by Sulfolobus turreted icosahedral virus (STIV) have been shown to produce unusual pyramid-like structures on the cell surface. These structures represent a virus-induced lysis mechanism that is present in Archaea and appears to be distinct from the holin/endolysin system...... described for DNA bacteriophages. This study investigated the STIV gene products required for pyramid formation in its host Sulfolobus solfataricus. Overexpression of STIV open reading frame (ORF) c92 in S. solfataricus alone is sufficient to produce the pyramid-like lysis structures in cells. Gene...

  18. PBDE: Structure-Activity Studies for the Inhibition of Hepatitis C Virus NS3 Helicase

    Directory of Open Access Journals (Sweden)

    Kazi Abdus Salam

    2014-04-01

    Full Text Available The helicase portion of the hepatitis C virus nonstructural protein 3 (NS3 is considered one of the most validated targets for developing direct acting antiviral agents. We isolated polybrominated diphenyl ether (PBDE 1 from a marine sponge as an NS3 helicase inhibitor. In this study, we evaluated the inhibitory effects of PBDE (1 on the essential activities of NS3 protein such as RNA helicase, ATPase, and RNA binding activities. The structure-activity relationship analysis of PBDE (1 against the HCV ATPase revealed that the biphenyl ring, bromine, and phenolic hydroxyl group on the benzene backbone might be a basic scaffold for the inhibitory potency.

  19. Structure of the cleavage-activated prefusion form of the parainfluenza virus 5 fusion protein.

    Science.gov (United States)

    Welch, Brett D; Liu, Yuanyuan; Kors, Christopher A; Leser, George P; Jardetzky, Theodore S; Lamb, Robert A

    2012-10-09

    The paramyxovirus parainfluenza virus 5 (PIV5) enters cells by fusion of the viral envelope with the plasma membrane through the concerted action of the fusion (F) protein and the receptor binding protein hemagglutinin-neuraminidase. The F protein folds initially to form a trimeric metastable prefusion form that is triggered to undergo large-scale irreversible conformational changes to form the trimeric postfusion conformation. It is thought that F refolding couples the energy released with membrane fusion. The F protein is synthesized as a precursor (F0) that must be cleaved by a host protease to form a biologically active molecule, F1,F2. Cleavage of F protein is a prerequisite for fusion and virus infectivity. Cleavage creates a new N terminus on F1 that contains a hydrophobic region, known as the FP, which intercalates target membranes during F protein refolding. The crystal structure of the soluble ectodomain of the uncleaved form of PIV5 F is known; here we report the crystal structure of the cleavage-activated prefusion form of PIV5 F. The structure shows minimal movement of the residues adjacent to the protease cleavage site. Most of the hydrophobic FP residues are buried in the uncleaved F protein, and only F103 at the newly created N terminus becomes more solvent-accessible after cleavage. The conformational freedom of the charged arginine residues that compose the protease recognition site increases on cleavage of F protein.

  20. Structure of the C-terminal domain of lettuce necrotic yellows virus phosphoprotein.

    Science.gov (United States)

    Martinez, Nicolas; Ribeiro, Euripedes A; Leyrat, Cédric; Tarbouriech, Nicolas; Ruigrok, Rob W H; Jamin, Marc

    2013-09-01

    Lettuce necrotic yellows virus (LNYV) is a prototype of the plant-adapted cytorhabdoviruses. Through a meta-prediction of disorder, we localized a folded C-terminal domain in the amino acid sequence of its phosphoprotein. This domain consists of an autonomous folding unit that is monomeric in solution. Its structure, solved by X-ray crystallography, reveals a lollipop-shaped structure comprising five helices. The structure is different from that of the corresponding domains of other Rhabdoviridae, Filoviridae, and Paramyxovirinae; only the overall topology of the polypeptide chain seems to be conserved, suggesting that this domain evolved under weak selective pressure and varied in size by the acquisition or loss of functional modules.

  1. Structure of the C-Terminal Domain of Lettuce Necrotic Yellows Virus Phosphoprotein

    Science.gov (United States)

    Martinez, Nicolas; Ribeiro, Euripedes A.; Leyrat, Cédric; Tarbouriech, Nicolas; Ruigrok, Rob W. H.

    2013-01-01

    Lettuce necrotic yellows virus (LNYV) is a prototype of the plant-adapted cytorhabdoviruses. Through a meta-prediction of disorder, we localized a folded C-terminal domain in the amino acid sequence of its phosphoprotein. This domain consists of an autonomous folding unit that is monomeric in solution. Its structure, solved by X-ray crystallography, reveals a lollipop-shaped structure comprising five helices. The structure is different from that of the corresponding domains of other Rhabdoviridae, Filoviridae, and Paramyxovirinae; only the overall topology of the polypeptide chain seems to be conserved, suggesting that this domain evolved under weak selective pressure and varied in size by the acquisition or loss of functional modules. PMID:23785215

  2. Structural view of the helicase reveals that Zika virus uses a conserved mechanism for unwinding RNA.

    Science.gov (United States)

    Li, Lei; Wang, Jin; Jia, Zhihui; Shaw, Neil

    2018-04-01

    Recent studies suggest a link between infection by Zika virus (ZIKV) and the development of neurological complications. The lack of ZIKV-specific therapeutics has alarmed healthcare professionals worldwide. Here, crystal structures of apo and AMPPNP- and Mn 2+ -bound forms of the essential helicase of ZIKV refined to 1.78 and 1.3 Å resolution, respectively, are reported. The structures reveal a conserved trimodular topology of the helicase. ATP and Mn 2+ are tethered between two RecA-like domains by conserved hydrogen-bonding interactions. The binding of ligands induces the movement of backbone Cα and side-chain atoms. Numerous solvent molecules are observed in the vicinity of the AMPPNP, suggesting a role in catalysis. These high-resolution structures could be useful for the design of inhibitors targeting the helicase of ZIKV for the treatment of infections caused by ZIKV.

  3. Evidence of pervasive biologically functional secondary structures within the genomes of eukaryotic single-stranded DNA viruses.

    Science.gov (United States)

    Muhire, Brejnev Muhizi; Golden, Michael; Murrell, Ben; Lefeuvre, Pierre; Lett, Jean-Michel; Gray, Alistair; Poon, Art Y F; Ngandu, Nobubelo Kwanele; Semegni, Yves; Tanov, Emil Pavlov; Monjane, Adérito Luis; Harkins, Gordon William; Varsani, Arvind; Shepherd, Dionne Natalie; Martin, Darren Patrick

    2014-02-01

    Single-stranded DNA (ssDNA) viruses have genomes that are potentially capable of forming complex secondary structures through Watson-Crick base pairing between their constituent nucleotides. A few of the structural elements formed by such base pairings are, in fact, known to have important functions during the replication of many ssDNA viruses. Unknown, however, are (i) whether numerous additional ssDNA virus genomic structural elements predicted to exist by computational DNA folding methods actually exist and (ii) whether those structures that do exist have any biological relevance. We therefore computationally inferred lists of the most evolutionarily conserved structures within a diverse selection of animal- and plant-infecting ssDNA viruses drawn from the families Circoviridae, Anelloviridae, Parvoviridae, Nanoviridae, and Geminiviridae and analyzed these for evidence of natural selection favoring the maintenance of these structures. While we find evidence that is consistent with purifying selection being stronger at nucleotide sites that are predicted to be base paired than at sites predicted to be unpaired, we also find strong associations between sites that are predicted to pair with one another and site pairs that are apparently coevolving in a complementary fashion. Collectively, these results indicate that natural selection actively preserves much of the pervasive secondary structure that is evident within eukaryote-infecting ssDNA virus genomes and, therefore, that much of this structure is biologically functional. Lastly, we provide examples of various highly conserved but completely uncharacterized structural elements that likely have important functions within some of the ssDNA virus genomes analyzed here.

  4. Pharmacological inhibition of feline immunodeficiency virus (FIV).

    Science.gov (United States)

    Mohammadi, Hakimeh; Bienzle, Dorothee

    2012-05-01

    Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses and causes an acquired immunodeficiency syndrome (AIDS) in domestic and non-domestic cats worldwide. Genome organization of FIV and clinical characteristics of the disease caused by the virus are similar to those of human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes and macrophages, and their replication cycle in infected cells is analogous. Due to marked similarity in genomic organization, virus structure, virus replication and disease pathogenesis of FIV and HIV, infection of cats with FIV is a useful tool to study and develop novel drugs and vaccines for HIV. Anti-retroviral drugs studied extensively in HIV infection have targeted different steps of the virus replication cycle: (1) inhibition of virus entry into susceptible cells at the level of attachment to host cell surface receptors and co-receptors; (2) inhibition of fusion of the virus membrane with the cell membrane; (3) blockade of reverse transcription of viral genomic RNA; (4) interruption of nuclear translocation and viral DNA integration into host genomes; (5) prevention of viral transcript processing and nuclear export; and (6) inhibition of virion assembly and maturation. Despite much success of anti-retroviral therapy slowing disease progression in people, similar therapy has not been thoroughly investigated in cats. In this article we review current pharmacological approaches and novel targets for anti-lentiviral therapy, and critically assess potentially suitable applications against FIV infection in cats.

  5. Sulfolobus turreted icosahedral virus c92 protein responsible for the formation of pyramid-like cellular lysis structures.

    Science.gov (United States)

    Snyder, Jamie C; Brumfield, Susan K; Peng, Nan; She, Qunxin; Young, Mark J

    2011-07-01

    Host cells infected by Sulfolobus turreted icosahedral virus (STIV) have been shown to produce unusual pyramid-like structures on the cell surface. These structures represent a virus-induced lysis mechanism that is present in Archaea and appears to be distinct from the holin/endolysin system described for DNA bacteriophages. This study investigated the STIV gene products required for pyramid formation in its host Sulfolobus solfataricus. Overexpression of STIV open reading frame (ORF) c92 in S. solfataricus alone is sufficient to produce the pyramid-like lysis structures in cells. Gene disruption of c92 within STIV demonstrates that c92 is an essential protein for virus replication. Immunolocalization of c92 shows that the protein is localized to the cellular membranes forming the pyramid-like structures.

  6. Spontaneous resolution of hemophagocytic syndrome associated with acute parvovirus B19 infection and concomitant Epstein-Barr virus reactivation in an otherwise healthy adult.

    Science.gov (United States)

    Larroche, C; Scieux, C; Honderlick, P; Piette, A M; Morinet, F; Blétry, O

    2002-10-01

    Reported here is the case of a patient who spontaneously recovered from hemophagocytic syndrome associated with acute B19 infection and concomitant Epstein-Barr virus reactivation. The previously healthy 37-year-old-man was hospitalized after 10 days of high fever, arthralgia and arthritis and was determined to have hemophagocytic syndrome. Immunoglobulin (Ig) M antibodies to Epstein-Barr virus (EBV) capsid antigen, early antigen and parvovirus B19 (B19) were found. B19 DNA and low-level EBV DNA were detected in bone marrow, serum and peripheral blood mononuclear cells. The patient recovered spontaneously without any treatment. Two months later anti-B19 IgG antibodies were detected, while at 9-month follow-up, anti-B19 IgM antibodies were no longer detectable and B19 DNA had disappeared from serum. To the best of our knowledge, this is the first report of spontaneous resolution of hemophagocytic syndrome associated with acute B19 infection and concomitant EBV reactivation in an otherwise healthy adult.

  7. Correlation among genetic, Euclidean, temporal, and herd ownership distances of porcine reproductive and respiratory syndrome virus strains in Quebec, Canada

    Directory of Open Access Journals (Sweden)

    Lambert Marie-Ève

    2012-06-01

    Full Text Available Abstract Background Porcine reproductive and respiratory syndrome (PRRS is a viral disease that has a major economic impact for the swine industry. Its control is mostly directed towards preventing its spread which requires a better understanding of the mechanisms of transmission of the virus between herds. The objectives of this study were to describe the genetic diversity and to assess the correlation among genetic, Euclidean and temporal distances and ownership to better understand pathways of transmission. Results A cross-sectional study was conducted on sites located in a high density area of swine production in Quebec. Geographical coordinates (longitude/latitude, date of submission and ownership were obtained for each site. ORF5 sequencing was attempted on PRRSV positive sites. Proportion of pairwise combinations of strains having ≥98% genetic homology were analysed according to Euclidean distances and ownership. Correlations between genetic, Euclidean and temporal distances and ownership were assessed using Mantel tests on continuous and binary matrices. Sensitivity of the correlations between genetic and Euclidean as well as temporal distances was evaluated for different Euclidean and temporal distance thresholds. An ORF5 sequence was identified for 132 of the 176 (75% PRRSV positive sites; 122 were wild-type strains. The mean (min-max genetic, Euclidean and temporal pairwise distances were 11.6% (0–18.7, 15.0 km (0.04-45.7 and 218 days (0–852, respectively. Significant positive correlations were observed between genetic and ownership, genetic and Euclidean and between genetic and temporal binary distances. The relationship between genetic and ownership suggests either common sources of animals or semen, employees, technical services or vehicles, whereas that between genetic and Euclidean binary distances is compatible with area spread of the virus. The latter correlation was observed only up to 5 km. Conclusions This study

  8. Knowledge, attitudes and practices regarding human immunodeficiency virus/acquired immune deficiency syndrome and sexually transmitted infections among health care providers in Lahore, Pakistan

    International Nuclear Information System (INIS)

    Khan, M.S.

    2010-01-01

    Human Immunodeficiency Virus (HIV) infection is a global problem of extraordinary dimensions and has so far resulted in nearly 25 million deaths worldwide. Health care providers (HCPs) are considered to play a pivotal role in the provision of preventive and curative services to individuals suffering from HIV/AIDS and sexually transmitted infections. Pakistan, which was previously categorised as having a low-prevalence, high-risk HIV epidemic, is now facing a concentrated HIV epidemic among its most at-risk populations such as injecting drug users. The objective of this study was to assess the knowledge, attitudes and reported practices relating to HIV/AIDS and STIs among private and public sector health care providers providing clinical services in areas where women sell sex. This was an exploratory quantitative study, where a structured questionnaire was administered in face-to-face interviews with 200 HCPs from the public and private sectors. Knowledge about AIDS and correct diagnosis of STIs were defined as according to the national guidelines of NACP. Pearson's chi-square analysis was performed to test associations between predictors and level of knowledge of STIs in each group separately. Multivariate logistic regression analysis was employed to indicate predicting factors for correct management of STIs. Forty-five percent of the HCPs had correct knowledge about the transmission and prevention of HIV, whereas 21% had seen a patient with advanced HIV infection, only two HCPs had been trained to manage such cases and 82% were not aware of syndromic management of STIs. Only 10% could cite the 'correct treatment' of gonorrhoea, syphilis and vaginal discharge. The odds of having the 'correct knowledge' of diagnosing gonorrhoea and syphilis were 2.1 (CI 95%, 1.2-3.8) if the HCP was a female medical doctor working in public sector. Further intensive training is needed to improve the ability of relevant HCPs to correctly diagnose and effectively treat patients

  9. Estimating Parameters Related to the Lifespan of Passively Transferred and Vaccine-Induced Porcine Reproductive and Respiratory Syndrome Virus Type I Antibodies by Modeling Field Data

    Directory of Open Access Journals (Sweden)

    Mathieu Andraud

    2018-01-01

    Full Text Available The outputs of epidemiological models are strongly related to the structure of the model and input parameters. The latter are defined by fitting theoretical concepts to actual data derived from field or experimental studies. However, some parameters may remain difficult to estimate and are subject to uncertainty or sensitivity analyses to determine their variation range and their global impact on model outcomes. As such, the evaluation of immunity duration is often a puzzling issue requiring long-term follow-up data that are, most of time, not available. The present analysis aims at characterizing the kinetics of antibodies against Porcine Reproductive and Respiratory Syndrome virus (PRRSv from longitudinal data sets. The first data set consisted in the serological follow-up of 22 vaccinated gilts during 21 weeks post-vaccination (PV. The second one gathered the maternally derived antibodies (MDAs kinetics in piglets from three different farms up to 14 weeks of age. The peak of the PV serological response against PRRSv was reached 6.9 weeks PV on average with an average duration of antibodies persistence of 26.5 weeks. In the monitored cohort of piglets, the duration of passive immunity was found relatively short, with an average duration of 4.8 weeks. The level of PRRSv-MDAs was found correlated with the dams’ antibody titer at birth, and the antibody persistence was strongly related to the initial MDAs titers in piglets. These results evidenced the importance of PRRSv vaccination schedule in sows, to optimize the delivery of antibodies to suckling piglets. These estimates of the duration of active and passive immunity could be further used as input parameters of epidemiological models to analyze their impact on the persistence of PRRSv within farms.

  10. O'nyong nyong virus molecular determinants of unique vector specificity reside in non-structural protein 3.

    Directory of Open Access Journals (Sweden)

    Kali D Saxton-Shaw

    Full Text Available O'nyong nyong virus (ONNV and Chikungunya virus (CHIKV are two closely related alphaviruses with very different infection patterns in the mosquito, Anopheles gambiae. ONNV is the only alphavirus transmitted by anopheline mosquitoes, but specific molecular determinants of infection of this unique vector specificity remain unidentified. Fifteen distinct chimeric viruses were constructed to evaluate both structural and non-structural regions of the genome and infection patterns were determined through artificial infectious feeds in An. gambiae with each of these chimeras. Only one region, non-structural protein 3 (nsP3, was sufficient to up-regulate infection to rates similar to those seen with parental ONNV. When ONNV non-structural protein 3 (nsP3 replaced nsP3 from CHIKV virus in one of the chimeric viruses, infection rates in An. gambiae went from 0% to 63.5%. No other single gene or viral region addition was able to restore infection rates. Thus, we have shown that a non-structural genome element involved in viral replication is a major element involved in ONNV's unique vector specificity.

  11. Differential Diagnosis Tool for Parkinsonian Syndrome Using Multiple Structural Brain Measures

    Directory of Open Access Journals (Sweden)

    Miho Ota

    2013-01-01

    Full Text Available Clinical differentiation of parkinsonian syndromes such as the Parkinson variant of multiple system atrophy (MSA-P and cerebellar subtype (MSA-C from Parkinson's disease is difficult in the early stage of the disease. To identify the correlative pattern of brain changes for differentiating parkinsonian syndromes, we applied discriminant analysis techniques by magnetic resonance imaging (MRI. T1-weighted volume data and diffusion tensor images were obtained by MRI in eighteen patients with MSA-C, 12 patients with MSA-P, 21 patients with Parkinson’s disease, and 21 healthy controls. They were evaluated using voxel-based morphometry and tract-based spatial statistics, respectively. Discriminant functions derived by step wise methods resulted in correct classification rates of 0.89. When differentiating these diseases with the use of three independent variables together, the correct classification rate was the same as that obtained with step wise methods. These findings support the view that each parkinsonian syndrome has structural deviations in multiple brain areas and that a combination of structural brain measures can help to distinguish parkinsonian syndromes.

  12. Duck hepatitis A virus structural proteins expressed in insect cells self-assemble into virus-like particles with strong immunogenicity in ducklings.

    Science.gov (United States)

    Wang, Anping; Gu, Lingling; Wu, Shuang; Zhu, Shanyuan

    2018-02-01

    Duck hepatitis A virus (DHAV), a non-enveloped ssRNA virus, can cause a highly contagious disease in young ducklings. The three capsid proteins of VP0, VP1 and VP3 are translated within a single large open reading frame (ORF) and hydrolyzed by protease 3CD. However, little is known on whether the recombinant viral structural proteins (VPs) expressed in insect cells could spontaneously assemble into virus-like particles (VLPs) and whether these VLPs could induce protective immunity in young ducklings. To address these issues, the structural polyprotein precursor gene P1 and the protease gene 3CD were amplified by PCR, and the recombinant proteins were expressed in insect cells using a baculovirus expression system for the characterization of their structures and immunogenicity. The recombinant proteins expressed in Sf9 cells were detected by indirect immunofluorescence assay and Western blot analysis. Electron microscopy showed that the recombinant proteins spontaneously assembled into VLPs in insect cells. Western blot analysis of the purified VLPs revealed that the VLPs were composed with the three structural proteins. In addition, vaccination with the VLPs induced high humoral immune response and provided strong protection. Therefore, our findings may provide a framework for development of new vaccines for the prevention of duck viral hepatitis. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. A new frailty syndrome: central obesity and frailty in older adults with the human immunodeficiency virus.

    Science.gov (United States)

    Shah, Krupa; Hilton, Tiffany N; Myers, Lauren; Pinto, Jonathan F; Luque, Amneris E; Hall, William J

    2012-03-01

    To evaluate the relationships between body composition and physical frailty in community-dwelling older adults with the human immunodeficiency virus (HIV) (HOA). Cross-sectional. Academic hospital-based infectious disease clinic in Rochester, New York. Forty community-dwelling HOA aged 50 and older undergoing antiretroviral therapy who were able to ambulate without assistive devices with a mean age of 58, a mean BMI of 29.0 kg/m(2), mean CD4 count of 569 cells/mL, and a mean duration since HIV diagnosis of 17 years; 28% were female and 57% Caucasian. Subjective and objective measures of functional status were evaluated using the Physical Performance Test (PPT), the graded treadmill test, knee strength, gait speed, balance, and the Functional Status Questionnaire (FSQ). Body composition was evaluated using dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). Sixty percent (25/40) of the participants met standard criteria for physical frailty. Frail (FR) and nonfrail (NF) participants were comparable in age, sex, CD4 count, and viral load. FR HOA had greater impairments in PPT, peak oxygen uptake, FSQ, walking speed, balance, and muscle quality than NF HOA. FR HOA had a greater body mass index (BMI), fat mass, and truncal fat with lipodystrophy. Moreover, PPT score was inversely related to trunk fat (correlation coefficient (r) = -0.34; P = .04) and ratio of intermuscular fat to total fat (r = -0.60; P = .02) after adjusting for covariates. HOA represent an emerging cohort of older adults who frequently experience frailty at a much younger age than the general older population. Central obesity and fat redistribution are important predictors of frailty in community-dwelling HOA. These findings suggest that physical frailty in HOA may be amenable to lifestyle interventions, especially exercise and diet therapy. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

  14. Characterisation of Structural Proteins from Chronic Bee Paralysis Virus (CBPV Using Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Aurore Chevin

    2015-06-01

    Full Text Available Chronic bee paralysis virus (CBPV is the etiological agent of chronic paralysis, an infectious and contagious disease in adult honeybees. CBPV is a positive single-stranded RNA virus which contains two major viral RNA fragments. RNA 1 (3674 nt and RNA 2 (2305 nt encode three and four putative open reading frames (ORFs, respectively. RNA 1 is thought to encode the viral RNA-dependent RNA polymerase (RdRp since the amino acid sequence derived from ORF 3 shares similarities with the RdRP of families Nodaviridae and Tombusviridae. The genomic organization of CBPV and in silico analyses have suggested that RNA 1 encodes non-structural proteins, while RNA 2 encodes structural proteins, which are probably encoded by ORFs 2 and 3. In this study, purified CBPV particles were used to characterize virion proteins by mass spectrometry. Several polypeptides corresponding to proteins encoded by ORF 2 and 3 on RNA 2 were detected. Their role in the formation of the viral capsid is discussed.

  15. Comparison of white spot syndrome virus infection resistance between Exopalaemon carinicauda and Litopenaeus vannamei under different salinity stresses

    Science.gov (United States)

    Ge, Qianqian; Yu, Ge; Sun, Ming; Li, Jitao; Li, Jian

    2017-12-01

    Exopalaemon carinicauda is one of the important economic shrimp species in China, and can tolerate a wide range of salinities. However, its disease resistance remains to be unclear in comparison with other shrimp species under salinity stress. In this study, the resistance to white spot syndrome virus (WSSV) of E. carinicauda and Litopenaeus vannamei was determined by comparing their hemocyanin (Hc) and phenoloxidase (PO) activities under different salinity stresses. In E. carinicauda, the PO activity and Hc gene transcript abundance showed a coherent pattern of increase and decrease while Hc content showed a slightly decrease with Vibrio anguillarum and WSSV infections. For both E. carinicauda and L. vannamei under salinity stress, the PO activity showed a positive correlation with the salinity while the Hc content and expression level of its gene increased significantly in salinities of 5, 15 and 25 g L-1. The survival rate of E. carinicauda with WSSV infection was higher than that of L. vannamei in the first 24 h under different salinity stresses. Drastic mortality of E.carinicauda and L. vannamei appeared at 48 h and 3 h post-injection, respectively. Furthermore, compared with L. vannamei, E. carinicauda displayed higher PO activity, Hc content and abundance of Hc gene mRNA. The results collectively indicated that Hc and PO have obviously functional connection in resisting pathogens and tolerating salinity stress, and PO activity and Hc gene mRNA abundance may reflect the resistance of shrimp to disease. E. carinicauda has higher level of immune potential than L. vannamei, suggesting its greater capacity in resisting pathogens under salinity stresses.

  16. Influence of white spot syndrome virus infection on hepatopancreas gene expression of `Huanghai No. 2' shrimp ( Fenneropenaeus chinensis)

    Science.gov (United States)

    Meng, Xianhong; Shi, Xiaoli; Kong, Jie; Luan, Sheng; Luo, Kun; Cao, Baoxiang; Liu, Ning; Lu, Xia; Li, Xupeng; Deng, Kangyu; Cao, Jiawang; Zhang, Yingxue; Zhang, Hengheng

    2017-10-01

    To elucidate the molecular response of shrimp hepatopancreas to white spot syndrome virus (WSSV) infection, microarray was applied to investigate the differentially expressed genes in the hepatopancreas of `Huanghai No. 2' ( Fenneropenaeus chinensis). A total of 59137 unigenes were designed onto a custom-made 60K Agilent chip. After infection, the gene expression profiles in the hepatopancreas of the shrimp with a lower viral load at early (48-96 h), peak (168-192 h) and late (264-288 h) infection phases were analyzed. Of 18704 differentially expressed genes, 6412 were annotated. In total, 5453 differentially expressed genes (1916 annotated) expressed at all three phases, and most of the annotated were either up- or down-regulated continuously. These genes function diversely in, for example, immune response, cytoskeletal system, signal transduction, stress resistance, protein synthesis and processing, metabolism among others. Some of the immune-related genes, including antilipopolysaccharide factor, Kazal-type proteinase inhibitor, C-type lectin and serine protease encoding genes, were up-regulated after WSSV infection. These genes have been reported to be involved in the anti-WSSV responses. The expression of genes related to the cytoskeletal system, including β-actin and myosin but without tubulin genes, were down-regulated after WSSV infection. Astakine was found for the first time in the WSSV-infected F. chinensis. To further confirm the expression of differentially expressed genes, quantitative real-time PCR was performed to test the expression of eight randomly selected genes and verified the reliability and accuracy of the microarray expression analysis. The data will provide valuable information to understanding the immune mechanism of shrimp's response to WSSV.

  17. Genotypic and geographical distribution of porcine reproductive and respiratory syndrome viruses in mainland China in 1996-2016.

    Science.gov (United States)

    Gao, Jia-Cong; Xiong, Jun-Yao; Ye, Chao; Chang, Xiao-Bo; Guo, Jin-Chao; Jiang, Cheng-Gang; Zhang, Gui-Hong; Tian, Zhi-Jun; Cai, Xue-Hui; Tong, Guang-Zhi; An, Tong-Qing

    2017-09-01

    Porcine reproductive and respiratory syndrome (PRRS) has caused huge economic losses to Chinese swine industry and remains a major threat since it was first reported in 1996. However, investigations of molecular epidemiological and genetic diversity of PRRS viruses (PRRSVs) in China were limited to a small number of representative strains collected in several areas. Moreover, lineage classifications reported by individual researchers were quite different. In the present study, we sequenced ORF5 sequences of 217 PRRSVs from clinical samples, retrieved all the available ORF5 sequences of PRRSVs isolated in China in 1996-2016 (n=2213) from GenBank, and systematically analyzed corresponding epidemiological data. NA-type PRRSVs in China were classified into five lineages: lineage 1, lineage 3, lineage 5, lineage 8, and lineage 9. Most strains in China belonged to lineage 8 (85.6%), with dominant strains being classified as sublineage 8.3 (78.3%). Importantly, the emerging lineage 1 and lineage 3 strains spread rapidly, and their proportions among circulating PRRSVs have significantly increased in recent years. The geographical distribution of different PRRSV lineages in each province was analyzed and possible inter-province transmission routes were outlined for main lineages and sublineages. To our knowledge, this study is the most comprehensive and extensive phylogeographical analysis of PRRSVs in China since PRRS outbreak in 1996. Our dataset can serve as a canonical standard for PRRSV classification and will help to study genetic evolution of PRRSV. The results of the present study may also improve prevention of PRRS in China. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Guillain-Barré Syndrome Associated With Zika Virus Infection in Martinique in 2016: A Prospective Study.

    Science.gov (United States)

    Rozé, Benoît; Najioullah, Fatiha; Fergé, Jean-Louis; Dorléans, Frédérique; Apetse, Kossivi; Barnay, Jose-Luis; Daudens-Vaysse, Elise; Brouste, Yannick; Césaire, Raymond; Fagour, Laurence; Valentino, Ruddy; Ledrans, Martine; Mehdaoui, Hossein; Abel, Sylvie; Leparc-Goffart, Isabelle; Signate, Aissatou; Cabié, André

    2017-10-16

    Guillain-Barré syndrome (GBS) has been reported to be associated with Zika virus (ZIKV) infection in case reports and retrospective studies, mostly on the basis of serological tests, with the problematic cross-reacting antibodies of the Flavivirus genus. Some GBS cases do not exhibit a high level of diagnostic certainty. This prospective study aimed to describe the clinical profiles and the frequency of GBS associated with ZIKV during the ZIKV outbreak in Martinique in 2016. We recorded prospective data from GBS meeting levels 1 or 2 of diagnostic certainty for the Brighton Collaboration, with proof of recent ZIKV infection and negative screening for etiologies of GBS. Of the sample of 34 patients with suspected GBS during the outbreak, 30 had a proven presence of GBS, and 23 had a recent ZIKV infection. The estimated GBS incidence rate ratio (2016 vs 2006-2015) was 4.52 (95% confidence interval, 2.80-7.64; P = .0001). Recent ZIKV infection was confirmed by urine reverse-transcription polymerase chain reaction (RT-PCR) analysis in 17 cases and by serology in 6 cases. Patients, 65% of whom were male, had a median age of 61 years (interquartile range, 56-71 years) and experienced severe GBS. Electrophysiological tests were consistent with the primary demyelinating form of the disease. ZIKV infection is usually benign, when symptomatic, but in countries at risk of ZIKV epidemics, adequate intensive care bed capacity is required for management of severe GBS cases. Arbovirus RNA detection by RT-PCR should be part of the management of GBS cases. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  19. Risky sexual behaviour and human immunodeficiency virus (HIV and acquired immune deficiency syndrome (AIDS among healthcare workers

    Directory of Open Access Journals (Sweden)

    Natasha Khamisa

    2018-01-01

    Full Text Available Background: South Africa is known to have one of the highest prevalence rates of human immunodeficiency virus (HIV and acquired immune deficiency syndrome (AIDS globally, with one in seven healthcare workers being HIV-positive. An HIV-positive healthcare workforce is less equipped to respond to the increasing spread of the epidemic. Objectives: Assessment of the factors contributing to high HIV prevalence rates among healthcare workers is important in planning the development of human resources. This review sought to identify and understand predominant risky sexual behaviours among healthcare workers in HIV and AIDS-affected countries. Methods: This study reviewed articles focusing on sexual behaviour among healthcare workers. Major health science databases (e.g. ProQuest, Cochrane, PubMed and CINAHL were searched for combinations of keywords including ‘healthcare workers’, ‘risky sexual behaviour’ and ‘HIV and AIDS’. Articles from a range of countries met inclusion and exclusion criteria. Results: Findings of the study revealed three main contributing factors: unprotected sex, multiple sex partners and sexual violence. Sexual violence emerged as the dominant risk factor in the majority of the studies. Most research was conducted in developed countries where the HIV infection rate is much lower than it is in developing countries. Conclusion: More research needs to be conducted in developing countries and appropriate strategies should be implemented to reduce sexual violence among healthcare workers. Appropriate procedures on reporting sexual violence coupled with education on HIV and AIDS as well as influencing attitudes and belief systems could assist in reducing the spread of HIV and AIDS within the healthcare workforce while minimising the effect on patient care.

  20. Peptide domains involved in the localization of the porcine reproductive and respiratory syndrome virus nucleocapsid protein to the nucleolus

    International Nuclear Information System (INIS)

    Rowland, Raymond R.R.; Schneider, Paula; Fang Ying; Wootton, Sarah; Yoo, Dongwan; Benfield, David A.

    2003-01-01

    The nucleocapsid (N) protein of porcine reproductive and respiratory syndrome virus (PRRSV) is the principal component of the viral nucleocapsid and localizes to the nucleolus. Peptide sequence analysis of the N protein of several North American isolates identified two potential nuclear localization signal (NLS) sequences located at amino acids 10-13 and 41-42, which were labeled NLS-1 and NLS-2, respectively. Peptides containing NLS-1 or NLS-2 were sufficient to accumulate enhanced green fluorescent protein (EGFP) in the nucleus. The inactivation of NLS-1 by site-directed mutagenesis or the deletion of the first 14 amino acids did not affect N protein localization to the nucleolus. The substitution of key lysine residues with uncharged amino acids in NLS-2 blocked nuclear/nucleolar localization. Site-directed mutagenesis within NLS-2 identified the sequence, KKNKK, as forming the core localization domain within NLS-2. Using an in vitro pull-down assay, the N protein was able to bind importin-α, importin-β nuclear transport proteins. The localization pattern of N-EGFP fusion peptides represented by a series of deletions from the C- and N-terminal ends of the N protein identified a region covering amino acids 41-72, which contained a nucleolar localization signal (NoLS) sequence. The 41-72 N peptide when fused to EGFP mimicked the nucleolar-cytoplasmic distribution of native N. These results identify a single NLS involved in the transport of N from the cytoplasm and into nucleus. An additional peptide sequence, overlapping NLS-2, is involved in the further targeting of N to the nucleolus

  1. Injected phage-displayed-VP28 vaccine reduces shrimp Litopenaeus vannamei mortality by white spot syndrome virus infection.

    Science.gov (United States)

    Solís-Lucero, G; Manoutcharian, K; Hernández-López, J; Ascencio, F

    2016-08-01

    White spot syndrome virus (WSSV) is the most important viral pathogen for the global shrimp industry causing mass mortalities with huge economic losses. Recombinant phages are capable of expressing foreign peptides on viral coat surface and act as antigenic peptide carriers bearing a phage-displayed vaccine. In this study, the full-length VP28 protein of WSSV, widely known as potential vaccine against infection in shrimp, was successfully cloned and expressed on M13 filamentous phage. The functionality and efficacy of this vaccine immunogen was demonstrated through immunoassay and in vivo challenge studies. In ELISA assay phage-displayed VP28 was bind to Litopenaeus vannamei immobilized hemocyte in contrast to wild-type M13 phage. Shrimps were injected with 2 × 10(10) cfu animal(-1) single dose of VP28-M13 and M13 once and 48 h later intramuscularly challenged with WSSV to test the efficacy of the vaccine against the infection. All dead challenged shrimps were PCR WSSV-positive. The accumulative mortality of the vaccinated and challenged shrimp groups was significantly lower (36.67%) than the unvaccinated group (66.67%). Individual phenoloxidase and superoxide dismutase activity was assayed on 8 and 48 h post-vaccination. No significant difference was found in those immunological parameters among groups at any sampled time evaluated. For the first time, phage display technology was used to express a recombinant vaccine for shrimp. The highest percentage of relative survival in vaccinated shrimp (RPS = 44.99%) suggest that the recombinant phage can be used successfully to display and deliver VP28 for farmed marine crustaceans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Risky sexual behaviour and human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) among healthcare workers.

    Science.gov (United States)

    Khamisa, Natasha; Mokgobi, Maboe

    2018-01-01

    South Africa is known to have one of the highest prevalence rates of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) globally, with one in seven healthcare workers being HIV-positive. An HIV-positive healthcare workforce is less equipped to respond to the increasing spread of the epidemic. Assessment of the factors contributing to high HIV prevalence rates among healthcare workers is important in planning the development of human resources. This review sought to identify and understand predominant risky sexual behaviours among healthcare workers in HIV and AIDS-affected countries. This study reviewed articles focusing on sexual behaviour among healthcare workers. Major health science databases (e.g. ProQuest, Cochrane, PubMed and CINAHL) were searched for combinations of keywords including 'healthcare workers', 'risky sexual behaviour' and 'HIV and AIDS'. Articles from a range of countries met inclusion and exclusion criteria. Findings of the study revealed three main contributing factors: unprotected sex, multiple sex partners and sexual violence. Sexual violence emerged as the dominant risk factor in the majority of the studies. Most research was conducted in developed countries where the HIV infection rate is much lower than it is in developing countries. More research needs to be conducted in developing countries and appropriate strategies should be implemented to reduce sexual violence among healthcare workers. Appropriate procedures on reporting sexual violence coupled with education on HIV and AIDS as well as influencing attitudes and belief systems could assist in reducing the spread of HIV and AIDS within the healthcare workforce while minimising the effect on patient care.

  3. Matrix Degradation in Human Immunodeficiency Virus Type 1-Associated Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome: A Prospective Observational Study.

    Science.gov (United States)

    Walker, Naomi F; Wilkinson, Katalin A; Meintjes, Graeme; Tezera, Liku B; Goliath, Rene; Peyper, Janique M; Tadokera, Rebecca; Opondo, Charles; Coussens, Anna K; Wilkinson, Robert J; Friedland, Jon S; Elkington, Paul T

    2017-07-01

    Extensive immunopathology occurs in human immunodeficiency virus (HIV)/tuberculosis (TB) coinfection, but the underlying molecular mechanisms are not well-defined. Excessive matrix metalloproteinase (MMP) activity is emerging as a key process but has not been systematically studied in HIV-associated TB. We performed a cross-sectional study of matrix turnover in HIV type 1 (HIV-1)-infected and -uninfected TB patients and controls, and a prospective cohort study of HIV-1-infected TB patients at risk of TB immune reconstitution inflammatory syndrome (TB-IRIS), in Cape Town, South Africa. Sputum and plasma MMP concentrations were quantified by Luminex, plasma procollagen III N-terminal propeptide (PIIINP) by enzyme-linked immunosorbent assay, and urinary lipoarabinomannan (LAM) by Alere Determine TB LAM assay. Peripheral blood mononuclear cells from healthy donors were cultured with Mycobacterium tuberculosis and extracellular matrix in a 3D model of TB granuloma formation. MMP activity differed between HIV-1-infected and -uninfected TB patients and corresponded with specific TB clinical phenotypes. HIV-1-infected TB patients had reduced pulmonary MMP concentrations, associated with reduced cavitation, but increased plasma PIIINP, compared to HIV-1-uninfected TB patients. Elevated extrapulmonary extracellular matrix turnover was associated with TB-IRIS, both before and during TB-IRIS onset. The predominant collagenase was MMP-8, which was likely neutrophil derived and M. tuberculosis-antigen driven. Mycobacterium tuberculosis-induced matrix degradation was suppressed by the MMP inhibitor doxycycline in vitro. MMP activity in TB differs by HIV-1 status and compartment, and releases matrix degradation products. Matrix turnover in HIV-1-infected patients is increased before and during TB-IRIS, informing novel diagnostic strategies. MMP inhibition is a potential host-directed therapy strategy for prevention and treatment of TB-IRIS. © The Author 2017. Published by Oxford

  4. [Monilethrix--rare syndrome of structural hair abnormalities].

    Science.gov (United States)

    Brzezińska-Wcisło, L; Bogdanowski, T; Szeremeta-Bazylewicz, G; Pierzchała, E

    1999-11-01

    Monilethrix is a rare structural disorder of hair. Characteristic abnormalities in the form of alternating thinning and fusiform thickening are observed in most of hair shafts that we call beaded hair. Macroscopic estimation shows lustreless, dry, rough, fragile hair. Trichological examination usually reveals a considerable percentage of anagenic hair. According to our own experiences and literature data systemic therapy (vitamins) and topical treatment (desquamative ointments) are not effective sufficiently. Spontaneous regression of symptoms often appears with time. Five cases of familial occurrence of monilethrix have been presented.

  5. Structure and function of A41, a vaccinia virus chemokine binding protein.

    Directory of Open Access Journals (Sweden)

    Mohammad W Bahar

    2008-01-01

    Full Text Available The vaccinia virus (VACV A41L gene encodes a secreted 30 kDa glycoprotein that is nonessential for virus replication but affects the host response to infection. The A41 protein shares sequence similarity with another VACV protein that binds CC chemokines (called vCKBP, or viral CC chemokine inhibitor, vCCI, and strains of VACV lacking the A41L gene induced stronger CD8+ T-cell responses than control viruses expressing A41. Using surface plasmon resonance, we screened 39 human and murine chemokines and identified CCL21, CCL25, CCL26 and CCL28 as A41 ligands, with Kds of between 8 nM and 118 nM. Nonetheless, A41 was ineffective at inhibiting chemotaxis induced by these chemokines, indicating it did not block the interaction of these chemokines with their receptors. However the interaction of A41 and chemokines was inhibited in a dose-dependent manner by heparin, suggesting that A41 and heparin bind to overlapping sites on these chemokines. To better understand the mechanism of action of A41 its crystal structure was solved to 1.9 A resolution. The protein has a globular beta sandwich structure similar to that of the poxvirus vCCI family of proteins, but there are notable structural differences, particularly in surface loops and electrostatic charge distribution. Structural modelling suggests that the binding paradigm as defined for the vCCI-chemokine interaction is likely to be conserved between A41 and its chemokine partners. Additionally, sequence analysis of chemokines binding to A41 identified a signature for A41 binding. The biological and structural data suggest that A41 functions by forming moderately strong (nM interactions with certain chemokines, sufficient to interfere with chemokine-glycosaminoglycan interactions at the cell surface (microM-nM and thereby to destroy the chemokine concentration gradient, but not strong enough to disrupt the (pM chemokine-chemokine receptor interactions.

  6. Enhanced perception in savant syndrome: patterns, structure and creativity.

    Science.gov (United States)

    Mottron, Laurent; Dawson, Michelle; Soulières, Isabelle

    2009-05-27

    According to the enhanced perceptual functioning (EPF) model, autistic perception is characterized by: enhanced low-level operations; locally oriented processing as a default setting; greater activation of perceptual areas during a range of visuospatial, language, working memory or reasoning tasks; autonomy towards higher processes; and superior involvement in intelligence. EPF has been useful in accounting for autistic relative peaks of ability in the visual and auditory modalities. However, the role played by atypical perceptual mechanisms in the emergence and character of savant abilities remains underdeveloped. We now propose that enhanced detection of patterns, including similarity within and among patterns, is one of the mechanisms responsible for operations on human codes, a type of material with which savants show particular facility. This mechanism would favour an orientation towards material possessing the highest level of internal structure, through the implicit detection of within- and between-code isomorphisms. A second mechanism, related to but exceeding the existing concept of redintegration, involves completion, or filling-in, of missing information in memorized or perceived units or structures. In the context of autistics' enhanced perception, the nature and extent of these two mechanisms, and their possible contribution to the creativity evident in savant performance, are explored.

  7. Small round structured virus associated with an outbreak of acute gastroenteritis in Chiba, Japan.

    Science.gov (United States)

    Kasuga, K; Tokieda, M; Ohtawara, M; Utagawa, E; Yamazaki, S

    1990-08-01

    In an outbreak of acute gastroenteritis which originated in a restaurant in Chiba, Japan, in December, 1987, small round structured virus (SRSV) particles were observed by electron microscopy in 14 of 16 stool specimens from patients. The particles were 30 to 35 nm in diameter, possessed amorphous surface structure surrounded by fine projections and had a buoyant density of 1.36 to 1.37 g/ml in cesium chloride. Serological responses to the SRSV were found by immune electron microscopy and Western blot (WB) assay in paired sera of 12 of 19 patients. Furthermore, WB analysis revealed that the antibody against SRSV was cross-reactive to other SRSV, Tokyo 86/510.

  8. Visceral fat is associated with brain structure independent of human immunodeficiency virus infection status.

    Science.gov (United States)

    Lake, Jordan E; Popov, Mikhail; Post, Wendy S; Palella, Frank J; Sacktor, Ned; Miller, Eric N; Brown, Todd T; Becker, James T

    2017-06-01

    The combined effects of human immunodeficiency virus (HIV), obesity, and elevated visceral adipose tissue (VAT) on brain structure are unknown. In a cross-sectional analysis of Multicenter AIDS Cohort Study (MACS) participants, we determined associations between HIV serostatus, adiposity, and brain structure. Men (133 HIV+, 84 HIV-) in the MACS Cardiovascular 2 and magnetic resonance imaging (MRI) sub-studies with CT-quantified VAT and whole brain MRI measured within 1 year were assessed. Voxel-based morphometry analyzed brain volumes. Men were stratified by elevated (eVAT, ≥100cm 2 ) or "normal" (nVAT, 25 kg/m 2 , smaller gray and white matter volumes, and larger cerebrospinal fluid volume than nVAT men. In multivariate analysis, hypertension, higher adiponectin, higher interleukin-6, age, diabetes mellitus, higher body mass index, and eVAT were associated with brain atrophy (p central nervous system effects may be amplified in this population.

  9. Epidemiological analysis of structural alterations of the nasal cavity associated with obstructive sleep apnea syndrome (OSA).

    Science.gov (United States)

    Mekhitarian Neto, Levon; Fava, Antonio Sérgio; Lopes, Hugo Canhete; Stamm, Aldo

    2005-01-01

    The objective of this paper is to demonstrate that structural alterations of the nasal cavity, e.g. septal deviation and conchal hypertrophy have high incidence in patients with sleep apnea and hypopnea syndrome and must be addressed with associated specific procedures of the syndrome. Clinical retrospective. A retrospective study of 200 patients was performed, with 196 male and 4 female, attended at the otorhinolaryngology ambulatory of Hospital Prof. Edmundo Vasconcelos and Unidade Paulista de Otorrinolaringologia, all of them subjected to polysomnography, otorhinolaryngological physical exam, endoscopy exam, and surgical treatment with nasal and pharyngeal procedures. All of them were subjected to pharyngeal procedure: uvulopalatopharyngoplasty or uvulopalatoplasty and nose procedure: 176 septoplasty with partial turbinectomy (88%) and 24 isolated turbinectomy, with satisfactory results. We can see that structural alterations of the nasal cavity have high incidence in patients with OSA.

  10. Some epitopes conservation in non structural 3 protein dengue virus serotype 4

    Directory of Open Access Journals (Sweden)

    Tegar A. P. Siregar

    2016-03-01

    Full Text Available AbstrakLatar belakang: Protein Non Struktural 3 (NS3 virus dengue menginduksi respon antibodi netralisasidan respon sel T CD4+ dan CD8+, serta berperan dalam replikasi virus. Protein NS3 memiliki epitopepitopsel T dan B yang terdapat perbedaan kelestarian pada berbagai strain virus dengue serotipe 4(DENV-4. Penelitian ini bertujuan untuk mengetahui kelestarian epitop sel T dan B pada protein NS3DENV-4 strain-strain dunia dan keempat serotipe virus dengue strain Indonesia.Metode: Penelitian ini dilakukan di Departemen Mikrobiologi Fakultas Kedokteran UI sejak Juni 2013 - April2014. Sekuens asam amino NS3 DENV-4 strain 081 didapatkan setelah produk PCR gen NS3 DENV-4 081disekuensing. Epitop-epitop sel T dan sel B protein NS3 DENV-4 081 dianalisis dan dibandingkan dengansekuens asam amino protein NS3 dari 124 strain DENV-4 di dunia dan keempat serotipe DENV strain Indonesia.Strain-strain dunia merupakan strain yang ada di benua Amerika (Venezuela, Colombia, dll dan Asia (Cina,Singapura, dll. Referensi posisi epitop sel T dan B protein NS3 diperoleh dari laporan penelitian terdahulu.Hasil: Delapan epitop sel T dan 2 epitop sel B dari protein NS3 DENV-4 081 ternyata identik dan lestaripada protein NS3 dari 124 strain DENV-4 dunia. Epitop sel B di posisi asam amino 537-544 pada proteinNS3 DENV-4 081 ternyata identik dan lestari dengan epitop sel B protein NS3 dari keempat serotipeDENV strain Indonesia.Kesimpulan: Kelestarian yang luas dari epitop sel T dan B pada hampir seluruh strain DENV-4 dunia danserotipe-serotipe DENV strain Indonesia. (Health Science Journal of Indonesia 2015;6:126-31Kata kunci: virus dengue, protein NS3, epitop sel T, epitop sel B AbstractBackground: Non Structural 3 (NS3 protein of dengue virus (DENV is known to induce antibody, CD4+and CD8+ T cell responses, and playing role in viral replication. NS3 protein has T and B cell epitopes,which has conservation difference between DENV-4 strains. This study aimed to identify

  11. Prediction of protein-protein interactions in dengue virus coat proteins guided by low resolution cryoEM structures

    Directory of Open Access Journals (Sweden)

    Srinivasan Narayanaswamy

    2010-06-01

    Full Text Available Abstract Background Dengue virus along with the other members of the flaviviridae family has reemerged as deadly human pathogens. Understanding the mechanistic details of these infections can be highly rewarding in developing effective antivirals. During maturation of the virus inside the host cell, the coat proteins E and M undergo conformational changes, altering the morphology of the viral coat. However, due to low resolution nature of the available 3-D structures of viral assemblies, the atomic details of these changes are still elusive. Results In the present analysis, starting from Cα positions of low resolution cryo electron microscopic structures the residue level details of protein-protein interaction interfaces of dengue virus coat proteins have been predicted. By comparing the preexisting structures of virus in different phases of life cycle, the changes taking place in these predicted protein-protein interaction interfaces were followed as a function of maturation process of the virus. Besides changing the current notion about the presence of only homodimers in the mature viral coat, the present analysis indicated presence of a proline-rich motif at the protein-protein interaction interface of the coat protein. Investigating the conservation status of these seemingly functionally crucial residues across other members of flaviviridae family enabled dissecting common mechanisms used for infections by these viruses. Conclusions Thus, using computational approach the present analysis has provided better insights into the preexisting low resolution structures of virus assemblies, the findings of which can be made use of in designing effective antivirals against these deadly human pathogens.

  12. High sensitivity but normal DNA-repair activity after UV irradiation in Epstein-Barr virus-transformed lymphoblastoid cell lines from Chediak-Higashi syndrome

    International Nuclear Information System (INIS)

    Tanaka, H.; Orii, T.

    1980-01-01

    We established lymphoblastoid cell lines from 2 children with Chediak-Higashi syndrome (CHS), 2 xeroderma pigmentosum (XP) patients and control donors after transformation of peripheral lymphocytes by Epstein-Barr virus (EBV). We used these lymphoblastoid cell lines to investigate repair activity after ultraviolet irradiation. Cell survival of both CHS lymphoblastoid cell lines after irradiation by UV and treatment by 4-nitroquinoline 1-oxide (4NQO) fell between those of the XP and control cells lines. Unscheduled DNA synthesis of CHS cells after UV irradiation occured at rates similar to those of control cells. (orig.)

  13. Determination of 5 '-leader sequences from radically disparate strains of porcine reproductive and respiratory syndrome virus reveals the presence of highly conserved sequence motifs

    DEFF Research Database (Denmark)

    Oleksiewicz, M.B.; Bøtner, Anette; Nielsen, Jens

    1999-01-01

    We determined the untranslated 5'-leader sequence for three different isolates of porcine reproductive and respiratory syndrome virus (PRRSV): pathogenic European- and American-types, as well as an American-type vaccine strain. 5'-leader from European- and American-type PRRSV differed in length...... (220 and 190 nt, respectively), and exhibited only approximately 50% nucleotide homology. Nevertheless, highly conserved areas were identified in the leader of all 3 PRRSV isolates, which constitute candidate motifs for binding of protein(s) involved in viral replication. These comparative data provide...

  14. Porcine reproductive and respiratory syndrome virus: Interlaboratory ring trial to evaluate real-time reverse transcription polymerase chain reaction detection methods

    DEFF Research Database (Denmark)

    Wernike, Kerstin; Bonilauri, Paolo; Dauber, Malte

    2012-01-01

    To compare the real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays used for the diagnosis of Porcine reproductive and respiratory syndrome virus (PRRSV), a Europe-wide interlaboratory ring trial was conducted. A variety of PRRSV strains including North American...... (NA) and European (EU) genotype isolates were analyzed by the participants. Great differences regarding qualitative diagnostics as well as analytical sensitivity were observed between the individual RT-qPCR systems, especially when investigating strains from the EU genotype. None of the assays...

  15. Cerebrospinal fluid anti-Epstein-Barr virus specific oligoclonal IgM and IgG bands in patients with clinically isolated and Guillain-Barré syndrome.

    Science.gov (United States)

    Ferraro, Diana; Galli, Veronica; Simone, Anna Maria; Bedin, Roberta; Vitetta, Francesca; Merelli, Elisa; Nichelli, Paolo Frigio; Sola, Patrizia

    2017-04-01

    Epstein-Barr virus (EBV) has been implicated in multiple sclerosis (MS) pathogenesis. We aimed to assess the frequency of EBV-specific IgG and IgM oligoclonal bands (OCB) in cerebrospinal fluid (CSF) of 50 patients with clinically isolated syndrome (CIS) and in 27 controls with Guillain-Barré syndrome (GBS). Furthermore, we assessed correlations between the presence of OCB and CIS patients' CSF, MRI, and clinical variables. There was no difference in the proportion of CIS and GB patients with positivity for anti-EBV-specific IgG/IgM OCB. There were no correlations between OCB and analyzed variables, nor were they predictive of a higher disability at 3 years.

  16. Divergent structural brain abnormalities between different genetic subtypes of children with Prader–Willi syndrome

    OpenAIRE

    Lukoshe, Akvile; White, Tonya; Schmidt, Marcus N; van der Lugt, Aad; Hokken-Koelega, Anita C

    2013-01-01

    Background Prader–Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical foc...

  17. Prevention of White Spot Syndrome Virus Infection on Penaeus monodon by Immersion in CEPM Extract of Avicennia sp. and Sonneratia sp.

    Directory of Open Access Journals (Sweden)

    D. Wahjuningrum

    2007-01-01

    Full Text Available The quality and survival rate are still being the problem that hampers the productivity of black tiger shrimp, Penaeus monodon culture.  Impaired quality of larval shrimp and environmental conditions can confer shrimp be infected by diseases, including viruses such as white spot syndrome virus (WSSV.  Prevention of disease infection using chemicals can offer negative impacts on water, pathogen resistance and consumers.  This study was conducted to examine the efficacy of an alternative prevention compound as liquid mangrove extract (CEPM from Avicennia sp. and Sonneratia sp. By immersion in different dose of CEPM, i.e. 250, 500, 750 and 1000 ppm, the patogenicity of WSSV was found to be different.  Patogenicity of WSSV decreased after treatment by CEPM, hence this could be used to induce shrimp immunity.  Optimum dose of CEPM was 250 ppm, which could increased survival rate of shrimp after challenging by WSSV, up to 98.4% shrimp survived. Keywrods: WSSV, black tiger shrimp, extract, Avicennia sp., Sonneratia sp.   ABSTRAK Kualitas dan kelangsungan hidup merupakan masalah yang masih membatasi produktivitas budidaya udang windu Penaeus monodon. Kondisi udang dan kualitas lingkungan yang kurang baik dapat menyebabkan udang terserang penyakit, termasuk yang disebabkan oleh virus termasuk white spot syndrome virus (WSSV. Upaya pengendaliannya menggunakan bahan kimia secara berlebih dapat menimbulkan dampak negatif bagi lingkungan perairan, kesehatan konsumen dan menimbulkan resistensi patogen. Penelitian ini dilakukan untuk mengetahui efektivitas bahan alternatif berupa cairan ekstrak pohon mangrove (CEPM dari jenis Avicennia sp. dan Sonneratia sp. sebagai upaya pencegahan. Dengan perendaman beberapa konsentrasi yang berbeda (250, 500, 750 dan 1000 ppm penggunaan cairan ekstrak pohon mangrove (CEPM Avicennia sp. dan Sonneratia sp., memberikan pengaruh yang berbeda terhadap patogenitas WSSV dan udang uji pada setiap perlakuan. Tingkat

  18. Crystal Structure of the Full-Length Feline Immunodeficiency Virus Capsid Protein Shows an N-Terminal β-Hairpin in the Absence of N-Terminal Proline

    Directory of Open Access Journals (Sweden)

    Christelle Folio

    2017-11-01

    Full Text Available Feline immunodeficiency virus (FIV is a member of the Retroviridae family. It is the causative agent of an acquired immunodeficiency syndrome (AIDS in cats and wild felines. Its capsid protein (CA drives the assembly of the viral particle, which is a critical step in the viral replication cycle. Here, the first atomic structure of full-length FIV CA to 1.67 Å resolution is determined. The crystallized protein exhibits an original tetrameric assembly, composed of dimers which are stabilized by an intermolecular disulfide bridge induced by the crystallogenesis conditions. The FIV CA displays a standard α-helical CA topology with two domains, separated by a linker shorter than other retroviral CAs. The β-hairpin motif at its amino terminal end, which interacts with nucleotides in HIV-1, is unusually long in FIV CA. Interestingly, this functional β-motif is formed in this construct in the absence of the conserved N-terminal proline. The FIV CA exhibits a cis Arg–Pro bond in the CypA-binding loop, which is absent in known structures of lentiviral CAs. This structure represents the first tri-dimensional structure of a functional, full-length FIV CA.

  19. Three-dimensional structure of the human immunodeficiency virus type 1 matrix protein.

    Science.gov (United States)

    Massiah, M A; Starich, M R; Paschall, C; Summers, M F; Christensen, A M; Sundquist, W I

    1994-11-25

    The HIV-1 matrix protein forms an icosahedral shell associated with the inner membrane of the mature virus. Genetic analyses have indicated that the protein performs important functions throughout the viral life-cycle, including anchoring the transmembrane envelope protein on the surface of the virus, assisting in viral penetration, transporting the proviral integration complex across the nuclear envelope, and localizing the assembling virion to the cell membrane. We now report the three-dimensional structure of recombinant HIV-1 matrix protein, determined at high resolution by nuclear magnetic resonance (NMR) methods. The HIV-1 matrix protein is the first retroviral matrix protein to be characterized structurally and only the fourth HIV-1 protein of known structure. NMR signal assignments required recently developed triple-resonance (1H, 13C, 15N) NMR methodologies because signals for 91% of 132 assigned H alpha protons and 74% of the 129 assignable backbone amide protons resonate within chemical shift ranges of 0.8 p.p.m. and 1 p.p.m., respectively. A total of 636 nuclear Overhauser effect-derived distance restraints were employed for distance geometry-based structure calculations, affording an average of 13.0 NMR-derived distance restraints per residue for the experimentally constrained amino acids. An ensemble of 25 refined distance geometry structures with penalties (sum of the squares of the distance violations) of 0.32 A2 or less and individual distance violations under 0.06 A was generated; best-fit superposition of ordered backbone heavy atoms relative to mean atom positions afforded root-mean-square deviations of 0.50 (+/- 0.08) A. The folded HIV-1 matrix protein structure is composed of five alpha-helices, a short 3(10) helical stretch, and a three-strand mixed beta-sheet. Helices I to III and the 3(10) helix pack about a central helix (IV) to form a compact globular domain that is capped by the beta-sheet. The C-terminal helix (helix V) projects away

  20. Structure of the extracellular domain of matrix protein 2 of influenza A virus in complex with a protective monoclonal antibody.

    Science.gov (United States)

    Cho, Ki Joon; Schepens, Bert; Seok, Jong Hyeon; Kim, Sella; Roose, Kenny; Lee, Ji-Hye; Gallardo, Rodrigo; Van Hamme, Evelien; Schymkowitz, Joost; Rousseau, Frederic; Fiers, Walter; Saelens, Xavier; Kim, Kyung Hyun

    2015-04-01

    The extracellular domain of influenza A virus matrix protein 2 (M2e) is conserved and is being evaluated as a quasiuniversal influenza A vaccine candidate. We describe the crystal structure at 1.6 Å resolution of M2e in complex with the Fab fragment of an M2e-specific monoclonal antibody that protects against influenza A virus challenge. This antibody binds M2 expressed on the surfaces of cells infected with influenza A virus. Five out of six complementary determining regions interact with M2e, and three highly conserved M2e residues are critical for this interaction. In this complex, M2e adopts a compact U-shaped conformation stabilized in the center by the highly conserved tryptophan residue in M2e. This is the first description of the three-dimensional structure of M2e. M2e of influenza A is under investigation as a universal influenza A vaccine, but its three-dimensional structure is unknown. We describe the structure of M2e stabilized with an M2e-specific monoclonal antibody that recognizes natural M2. We found that the conserved tryptophan is positioned in the center of the U-shaped structure of M2e and stabilizes its conformation. The structure also explains why previously reported in vivo escape viruses, selected with a similar monoclonal antibody, carried proline residue substitutions at position 10 in M2. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. Structural Transitions and Energy Landscape for Cowpea Chlorotic Mottle Virus Capsid Mechanics from Nanomanipulation in Vitro and in Silico

    Science.gov (United States)

    Kononova, Olga; Snijder, Joost; Brasch, Melanie; Cornelissen, Jeroen; Dima, Ruxandra I.; Marx, Kenneth A.; Wuite, Gijs J. L.; Roos, Wouter H.; Barsegov, Valeri

    2013-10-01

    Physical properties of capsids of plant and animal viruses are important factors in capsid self-assembly, survival of viruses in the extracellular environment, and their cell infectivity. Virus shells can have applications as nanocontainers and delivery vehicles in biotechnology and medicine. Combined AFM experiments and computational modeling on sub-second timescales of the indentation nanomechanics of Cowpea Chlorotic Mottle Virus (CCMV) capsid show that the capsid's physical properties are dynamic and local characteristics of the structure, which depend on the magnitude and geometry of mechanical input. Surprisingly, under large deformations the CCMV capsid transitions to the collapsed state without substantial local structural alterations. The enthalpy change in this deformation state dH = 11.5 - 12.8 MJ/mol is mostly due to large-amplitude out-of-plane excitations, which contribute to the capsid bending, and the entropy change TdS = 5.1 - 5.8 MJ/mol is mostly due to coherent in-plane rearrangements of protein chains, which result in the capsid stiffening. Dynamic coupling of these modes defines the extent of elasticity and reversibility of capsid mechanical deformation. This emerging picture illuminates how unique physico-chemical properties of protein nanoshells help define their structure and morphology, and determine their viruses' biological function.

  2. Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach.

    Directory of Open Access Journals (Sweden)

    Arturo Blazquez-Navarro

    2018-05-01

    Full Text Available BK virus (BKV associated nephropathy affects 1-10% of kidney transplant recipients, leading to graft failure in about 50% of cases. Immune responses against different BKV antigens have been shown to have a prognostic value for disease development. Data currently suggest that the structural antigens and regulatory antigens of BKV might each trigger a different mode of action of the immune response. To study the influence of different modes of action of the cellular immune response on BKV clearance dynamics, we have analysed the kinetics of BKV plasma load and anti-BKV T cell response (Elispot in six patients with BKV associated nephropathy using ODE modelling. The results show that only a small number of hypotheses on the mode of action are compatible with the empirical data. The hypothesis with the highest empirical support is that structural antigens trigger blocking of virus production from infected cells, whereas regulatory antigens trigger an acceleration of death of infected cells. These differential modes of action could be important for our understanding of BKV resolution, as according to the hypothesis, only regulatory antigens would trigger a fast and continuous clearance of the viral load. Other hypotheses showed a lower degree of empirical support, but could potentially explain the clearing mechanisms of individual patients. Our results highlight the heterogeneity of the dynamics, including the delay between immune response against structural versus regulatory antigens, and its relevance for BKV clearance. Our modelling approach is the first that studies the process of BKV clearance by bringing together viral and immune kinetics and can provide a framework for personalised hypotheses generation on the interrelations between cellular immunity and viral dynamics.

  3. Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach.

    Science.gov (United States)

    Blazquez-Navarro, Arturo; Schachtner, Thomas; Stervbo, Ulrik; Sefrin, Anett; Stein, Maik; Westhoff, Timm H; Reinke, Petra; Klipp, Edda; Babel, Nina; Neumann, Avidan U; Or-Guil, Michal

    2018-05-01

    BK virus (BKV) associated nephropathy affects 1-10% of kidney transplant recipients, leading to graft failure in about 50% of cases. Immune responses against different BKV antigens have been shown to have a prognostic value for disease development. Data currently suggest that the structural antigens and regulatory antigens of BKV might each trigger a different mode of action of the immune response. To study the influence of different modes of action of the cellular immune response on BKV clearance dynamics, we have analysed the kinetics of BKV plasma load and anti-BKV T cell response (Elispot) in six patients with BKV associated nephropathy using ODE modelling. The results show that only a small number of hypotheses on the mode of action are compatible with the empirical data. The hypothesis with the highest empirical support is that structural antigens trigger blocking of virus production from infected cells, whereas regulatory antigens trigger an acceleration of death of infected cells. These differential modes of action could be important for our understanding of BKV resolution, as according to the hypothesis, only regulatory antigens would trigger a fast and continuous clearance of the viral load. Other hypotheses showed a lower degree of empirical support, but could potentially explain the clearing mechanisms of individual patients. Our results highlight the heterogeneity of the dynamics, including the delay between immune response against structural versus regulatory antigens, and its relevance for BKV clearance. Our modelling approach is the first that studies the process of BKV clearance by bringing together viral and immune kinetics and can provide a framework for personalised hypotheses generation on the interrelations between cellular immunity and viral dynamics.

  4. Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

    International Nuclear Information System (INIS)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram; Kerr, Iain D.; Min, Jinrong

    2015-01-01

    The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot’s syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants

  5. Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); Kerr, Iain D., E-mail: ikerr@myriad.com [Myriad Genetic Laboratories Inc., 320 Wakara Way, Salt Lake City, UT 84108 (United States); Min, Jinrong, E-mail: ikerr@myriad.com [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); University of Toronto, Toronto, ON M5G 1L7 (Canada)

    2015-07-28

    The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot’s syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.

  6. High affinity human antibody fragments to dengue virus non-structural protein 3.

    Directory of Open Access Journals (Sweden)

    Nicole J Moreland

    Full Text Available BACKGROUND: The enzyme activities catalysed by flavivirus non-structural protein 3 (NS3 are essential for virus replication. They are distributed between the N-terminal protease domain in the first one-third and the C-terminal ATPase/helicase and nucleoside 5' triphosphatase domain which forms the remainder of the 618-aa long protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, dengue full-length NS3 protein with residues 49 to 66 of NS2B covalently attached via a flexible linker, was used as bait in biopanning with a naïve human Fab phage-display library. Using a range of truncated constructs spanning the NS2B cofactor region and the full-length NS3, 10 unique Fab were identified and characterized. Of these, monoclonal Fab 3F8 was shown to bind α3″ (residues 526 through 531 within subdomain III of the helicase domain. The antibody inhibits the ATPase and helicase activites of NS3 in biochemical assays and reduces DENV replication in HEK293 cells that were previously transfected with Fab 3F8 compared with mock transfected cells. CONCLUSIONS/SIGNIFICANCE: Antibodies such as 3F8 are valuable tools for studying the molecular mechanisms of flaviviral replication and for the monospecific detection of replicating dengue virus in vivo.

  7. Crystal Structure of the Conserved Herpes Virus Fusion Regulator Complex gH–gL

    Energy Technology Data Exchange (ETDEWEB)

    Chowdary, T.; Cairns, T; Atanasiu, D; Cohen, G; Eisenberg, R; Heldwein, E

    2010-01-01

    Herpesviruses, which cause many incurable diseases, infect cells by fusing viral and cellular membranes. Whereas most other enveloped viruses use a single viral catalyst called a fusogen, herpesviruses, inexplicably, require two conserved fusion-machinery components, gB and the heterodimer gH-gL, plus other nonconserved components. gB is a class III viral fusogen, but unlike other members of its class, it does not function alone. We determined the crystal structure of the gH ectodomain bound to gL from herpes simplex virus 2. gH-gL is an unusually tight complex with a unique architecture that, unexpectedly, does not resemble any known viral fusogen. Instead, we propose that gH-gL activates gB for fusion, possibly through direct binding. Formation of a gB-gH-gL complex is critical for fusion and is inhibited by a neutralizing antibody, making the gB-gH-gL interface a promising antiviral target.

  8. Crystal structure of the conserved herpes virus fusion regulator complex gH-gL

    Energy Technology Data Exchange (ETDEWEB)

    Chowdary, Tirumala K; Cairns, Tina M; Atanasiu, Doina; Cohen, Gary H; Eisenberg, Roselyn J; Heldwein, Ekaterina E [UPENN; (Tufts-MED)

    2010-09-13

    Herpesviruses, which cause many incurable diseases, infect cells by fusing viral and cellular membranes. Whereas most other enveloped viruses use a single viral catalyst called a fusogen, herpesviruses, inexplicably, require two conserved fusion-machinery components, gB and the heterodimer gH-gL, plus other nonconserved components. gB is a class III viral fusogen, but unlike other members of its class, it does not function alone. We determined the crystal structure of the gH ectodomain bound to gL from herpes simplex virus 2. gH-gL is an unusually tight complex with a unique architecture that, unexpectedly, does not resemble any known viral fusogen. Instead, we propose that gH-gL activates gB for fusion, possibly through direct binding. Formation of a gB-gH-gL complex is critical for fusion and is inhibited by a neutralizing antibody, making the gB-gH-gL interface a promising antiviral target.

  9. Identification of structural protein-protein interactions of herpes simplex virus type 1.

    Science.gov (United States)

    Lee, Jin H; Vittone, Valerio; Diefenbach, Eve; Cunningham, Anthony L; Diefenbach, Russell J

    2008-09-01

    In this study we have defined protein-protein interactions between the structural proteins of herpes simplex virus type 1 (HSV-1) using a LexA yeast two-hybrid system. The majority of the capsid, tegument and envelope proteins of HSV-1 were screened in a matrix approach. A total of 40 binary interactions were detected including 9 out of 10 previously identified tegument-tegument interactions (Vittone, V., Diefenbach, E., Triffett, D., Douglas, M.W., Cunningham, A.L., and Diefenbach, R.J., 2005. Determination of interactions between tegument proteins of herpes simplex virus type 1. J. Virol. 79, 9566-9571). A total of 12 interactions involving the capsid protein pUL35 (VP26) and 11 interactions involving the tegument protein pUL46 (VP11/12) were identified. The most significant novel interactions detected in this study, which are likely to play a role in viral assembly, include pUL35-pUL37 (capsid-tegument), pUL46-pUL37 (tegument-tegument) and pUL49 (VP22)-pUS9 (tegument-envelope). This information will provide further insights into the pathways of HSV-1 assembly and the identified interactions are potential targets for new antiviral drugs.

  10. Effect of grazers and viruses on bacterial community structure and production in two contrasting trophic lakes

    Directory of Open Access Journals (Sweden)

    Domaizon Isabelle

    2011-04-01

    Full Text Available Abstract Background Over the last 30 years, extensive studies have revealed the crucial roles played by microbes in aquatic ecosystems. It has been shown that bacteria, viruses and protozoan grazers are dominant in terms of abundance and biomass. The frequent interactions between these microbiological compartments are responsible for strong trophic links from dissolved organic matter to higher trophic levels, via heterotrophic bacteria, which form the basis for the important biogeochemical roles of microbial food webs in aquatic ecosystems. To gain a better understanding of the interactions between bacteria, viruses and flagellates in lacustrine ecosystems, we investigated the effect of protistan bacterivory on bacterial abundance, production and structure [determined by 16S rRNA PCR-DGGE], and viral abundance and activity of two lakes of contrasting trophic status. Four experiments were conducted in the oligotrophic Lake Annecy and the mesotrophic Lake Bourget over two seasons (early spring vs. summer using a fractionation approach. In situ dark vs. light incubations were performed to consider the effects of the different treatments in the presence and absence of phototrophic activity. Results The presence of grazers (i.e. Conclusions Our results highlight the importance of a synergistic effect, i.e. the positive influence of grazers on viral activities in sustaining (directly and indirectly bacterial production and affecting composition, in both oligotrophic and mesotrophic lakes.

  11. Outbreak of small round structured virus gastroenteritis arose after kitchen assistant vomited.

    Science.gov (United States)

    Patterson, W; Haswell, P; Fryers, P T; Green, J

    1997-06-27

    A wedding reception at a North Yorkshire hotel was followed by an explosive outbreak of gastroenteritis. The attack rate among the 111 guests was 50% and vomiting was a predominant feature. The results of laboratory and epidemiological investigations were consistent with a common source outbreak of small round structured virus (SRSV) infection genotype II. The source of the outbreak was traced to a kitchen assistant who suddenly became ill on the eve of the reception and vomited into a sink used for preparing vegetables. The sink was cleaned with a chlorine based disinfectant and used the next morning to prepare a potato salad, subsequently identified as the vehicle of infection in a cohort study of guests (odds ratio 3.21; CI 1.78-5.78, p = 0.0001). No other food was associated with illness. The outbreak provides further supporting evidence of the importance of vomiting in the transmission of SRSV infection, highlights the virulence of this group of viruses, and indicates their relative resistance to environmental disinfection and decontamination. It also highlights the need for the adequate training of catering staff and the implementation and enforcement of food hygiene regulations.

  12. Structures of protective antibodies reveal sites of vulnerability on Ebola virus.

    Science.gov (United States)

    Murin, Charles D; Fusco, Marnie L; Bornholdt, Zachary A; Qiu, Xiangguo; Olinger, Gene G; Zeitlin, Larry; Kobinger, Gary P; Ward, Andrew B; Saphire, Erica Ollmann

    2014-12-02

    Ebola virus (EBOV) and related filoviruses cause severe hemorrhagic fever, with up to 90% lethality, and no treatments are approved for human use. Multiple recent outbreaks of EBOV and the likelihood of future human exposure highlight the need for pre- and postexposure treatments. Monoclonal antibody (mAb) cocktails are particularly attractive candidates due to their proven postexposure efficacy in nonhuman primate models of EBOV infection. Two candidate cocktails, MB-003 and ZMAb, have been extensively evaluated in both in vitro and in vivo studies. Recently, these two therapeutics have been combined into a new cocktail named ZMapp, which showed increased efficacy and has been given compassionately to some human patients. Epitope information and mechanism of action are currently unknown for most of the component mAbs. Here we provide sin