viral nonstructural proteins

Summary

Summary: Proteins encoded by a VIRAL GENOME that are produced in the organisms they infect, but not packaged into the VIRUS PARTICLES. Some of these proteins may play roles within the infected cell during VIRUS REPLICATION or act in regulation of virus replication or VIRUS ASSEMBLY.

Top Publications

  1. ncbi Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
    Etienne Meylan
    Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Nature 437:1167-72. 2005
  2. ncbi The multifunctional NS1 protein of influenza A viruses
    Benjamin G Hale
    Centre for Biomolecular Sciences, University of St Andrews, St Andrews, Fife KY16 9ST, UK
    J Gen Virol 89:2359-76. 2008
  3. ncbi The lipid droplet is an important organelle for hepatitis C virus production
    Yusuke Miyanari
    Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606 8507, Japan
    Nat Cell Biol 9:1089-97. 2007
  4. pmc Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication
    Keril J Blight
    Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    J Virol 76:13001-14. 2002
  5. ncbi Complete replication of hepatitis C virus in cell culture
    Brett D Lindenbach
    Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 309:623-6. 2005
  6. ncbi Antiviral strategies in hepatitis C virus infection
    Christoph Sarrazin
    Klinikum der JW Goethe Universität, Medizinische Klinik 1, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany
    J Hepatol 56:S88-100. 2012
  7. ncbi High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever
    Daniel H Libraty
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, MA 01655, USA
    J Infect Dis 186:1165-8. 2002
  8. ncbi Discovery and development of telaprevir: an NS3-4A protease inhibitor for treating genotype 1 chronic hepatitis C virus
    Ann D Kwong
    Vertex Pharmaceuticals, Cambridge, Massachusetts, USA
    Nat Biotechnol 29:993-1003. 2011
  9. pmc Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I
    Michaela Ulrike Gack
    Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA
    Cell Host Microbe 5:439-49. 2009
  10. ncbi RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates
    Andreas Pichlmair
    Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK
    Science 314:997-1001. 2006

Detail Information

Publications384 found, 100 shown here

  1. ncbi Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
    Etienne Meylan
    Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Nature 437:1167-72. 2005
    ..Cardif thus functions as an adaptor, linking the cytoplasmic dsRNA receptor RIG-I to the initiation of antiviral programmes...
  2. ncbi The multifunctional NS1 protein of influenza A viruses
    Benjamin G Hale
    Centre for Biomolecular Sciences, University of St Andrews, St Andrews, Fife KY16 9ST, UK
    J Gen Virol 89:2359-76. 2008
    ....
  3. ncbi The lipid droplet is an important organelle for hepatitis C virus production
    Yusuke Miyanari
    Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606 8507, Japan
    Nat Cell Biol 9:1089-97. 2007
    ..This study reveals a novel function of LDs in the assembly of infectious HCV and provides a new perspective on how viruses usurp cellular functions...
  4. pmc Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication
    Keril J Blight
    Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    J Virol 76:13001-14. 2002
    ....
  5. ncbi Complete replication of hepatitis C virus in cell culture
    Brett D Lindenbach
    Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 309:623-6. 2005
    ..HCVcc replication was inhibited by interferon-alpha and by several HCV-specific antiviral compounds, suggesting that this in vitro system will aid in the search for improved antivirals...
  6. ncbi Antiviral strategies in hepatitis C virus infection
    Christoph Sarrazin
    Klinikum der JW Goethe Universität, Medizinische Klinik 1, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany
    J Hepatol 56:S88-100. 2012
    ..However, new drugs may be associated with troublesome side effects and drugdrug interactions, and the ideal IFN-free DAA combination remains to be found...
  7. ncbi High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever
    Daniel H Libraty
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, MA 01655, USA
    J Infect Dis 186:1165-8. 2002
    ..An elevated free sNS1 level (> or =600 ng/mL) within 72 h of illness onset identified patients at risk for developing DHF...
  8. ncbi Discovery and development of telaprevir: an NS3-4A protease inhibitor for treating genotype 1 chronic hepatitis C virus
    Ann D Kwong
    Vertex Pharmaceuticals, Cambridge, Massachusetts, USA
    Nat Biotechnol 29:993-1003. 2011
    ..Lessons learned from the development of telaprevir suggest that makers of innovative medicines cannot rely solely on traditional drug discovery metrics, but must develop innovative, scientifically guided pathways for success...
  9. pmc Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I
    Michaela Ulrike Gack
    Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA
    Cell Host Microbe 5:439-49. 2009
    ..Our findings reveal a mechanism by which influenza virus inhibits host IFN response and also emphasize the vital role of TRIM25 in modulating antiviral defenses...
  10. ncbi RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates
    Andreas Pichlmair
    Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK
    Science 314:997-1001. 2006
    ....
  11. ncbi Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect
    Min Gao
    Department of Virology, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    Nature 465:96-100. 2010
    ....
  12. pmc Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment
    Simon Reiss
    The Department of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany
    Cell Host Microbe 9:32-45. 2011
    ..Our analysis suggests that the direct activation of a lipid kinase by HCV NS5A contributes critically to the integrity of the membranous viral replication complex...
  13. pmc Enzyme-linked immunosorbent assay specific to Dengue virus type 1 nonstructural protein NS1 reveals circulation of the antigen in the blood during the acute phase of disease in patients experiencing primary or secondary infections
    Sophie Alcon
    Unité des Arbovirus et Virus des Fièvres Hémorragiques, Institut Pasteur, 75724 Paris Cedex 15, France
    J Clin Microbiol 40:376-81. 2002
    ..Furthermore, NS1 circulation in the bloodstream of patients during the clinical phase of the disease suggests a contribution of the nonstructural protein to dengue virus pathogenesis...
  14. ncbi Interplay between influenza A virus and the innate immune signaling
    Christina Ehrhardt
    Institute of Molecular Virology IMV, Center for Molecular Biology of Inflammation ZMBE, Westfaelische Wilhelms University, Muenster, Germany
    Microbes Infect 12:81-7. 2010
    ..Further we summarize progress related to recently identified IFN induced proteins and the role of RNA interference in the context of IAV infection...
  15. pmc Multiple anti-interferon actions of the influenza A virus NS1 protein
    Georg Kochs
    Department of Virology, University of Freiburg, D 79008 Freiburg, Germany
    J Virol 81:7011-21. 2007
    ..Our results demonstrate the capacity of FLUAV NS1 to suppress the antiviral host defense at multiple levels and the existence of strain-specific differences that may modulate virus pathogenicity...
  16. ncbi Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement
    Panisadee Avirutnan
    Medical Molecular Biology Unit, Siriraj Hospital, Mahidol University, Bangkok, Thailand
    J Infect Dis 193:1078-88. 2006
    ..Thirty years ago, complement activation was proposed to be a key underlying event, but the cause of complement activation has remained unknown...
  17. pmc Architects of assembly: roles of Flaviviridae non-structural proteins in virion morphogenesis
    Catherine L Murray
    The Rockefeller University, New York, NY 10065, USA
    Nat Rev Microbiol 6:699-708. 2008
    ..Pinpointing the roles of Flaviviridae proteins in virion production could reveal new avenues for antiviral therapeutics...
  18. pmc Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter
    U J Buchholz
    Department of Clinical Virology, Federal Research Center for Virus Diseases of Animals, D 72076 Tubingen, Germany
    J Virol 73:251-9. 1999
    ....
  19. pmc Influenza virus targets the mRNA export machinery and the nuclear pore complex
    Neal Satterly
    Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9039, USA
    Proc Natl Acad Sci U S A 104:1853-8. 2007
    ..These findings demonstrate previously undescribed influenza-mediated viral-host interactions and provide insights into potential molecular therapies that may interfere with influenza infection...
  20. pmc Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans
    Rebecca J Garten
    WHO Collaborating Center for Influenza, Centers for Disease Control and Prevention CDC, Atlanta, GA 30333, USA
    Science 325:197-201. 2009
    ..Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1)...
  21. ncbi Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir
    Christoph Sarrazin
    Klinik fur Innere Medizin II, Universitat des Saarlandes, Homburg Saar, Germany
    Gastroenterology 132:1767-77. 2007
    ..4A protease inhibitor, has shown strong antiviral activity in phase 1 clinical studies. Because of high levels of HCV replication and the low fidelity of HCV polymerase, selection of resistant isolates during therapy may occur...
  22. ncbi Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus-infected patients
    Simone Susser
    JW Goethe University Hospital, Frankfurt, Germany
    Hepatology 50:1709-18. 2009
    ..Mathematical modeling revealed impaired replicative fitness for all single mutations, whereas for combined mutations a relative increase of replication efficiency was suggested...
  23. ncbi Hepatitis C virus resistance to protease inhibitors
    Philippe Halfon
    Virological Departement Laboratoire Alphabio, Hopital Ambroise Pare, Marseille, France
    J Hepatol 55:192-206. 2011
    ....
  24. ncbi Differential efficacy of protease inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant viruses
    Judith M Gottwein
    Copenhagen Hepatitis C Program CO HEP, Department of Infectious Diseases and Clinical Research Centre, Copenhagen University Hospital, Hvidovre and Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
    Gastroenterology 141:1067-79. 2011
    ..Because there are limited or no data on efficacy against HCV genotypes 2-7, we aimed at developing recombinant infectious cell culture systems expressing genotype-specific nonstructural (NS) protein 3 protease (NS3P)...
  25. pmc Cyclophilin A interacts with domain II of hepatitis C virus NS5A and stimulates RNA binding in an isomerase-dependent manner
    Toshana L Foster
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Mount Preston Street, Leeds LS2 9JT, United Kingdom
    J Virol 85:7460-4. 2011
    ..This study provides an insight into the molecular mechanism of CypA activity during HCV replication and further validates the use of CypA inhibitors in HCV therapy...
  26. pmc Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF
    Kui Li
    Department of Microbiology and Immunology and Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555 1019, USA
    Proc Natl Acad Sci U S A 102:2992-7. 2005
    ..This uniquely broad mechanism of immune evasion potentially limits expression of multiple host defense genes, thereby promoting persistent infections with this medically important virus...
  27. pmc Kinetics of plasma viremia and soluble nonstructural protein 1 concentrations in dengue: differential effects according to serotype and immune status
    Huynh T L Duyen
    Oxford University Clinical Research Unit, Churchill Hospital, Oxford, UK
    J Infect Dis 203:1292-300. 2011
    ..Our findings identify clear serotype and immune-status related effects on the dynamics of dengue viremia and sNS1 responses, together with associations with important clinical parameters...
  28. pmc Dengue virus type 1 nonstructural glycoprotein NS1 is secreted from mammalian cells as a soluble hexamer in a glycosylation-dependent fashion
    M Flamand
    Unité des Arbovirus et Virus des Fièvres Hémorragiques, Institut Pasteur, 75724 Paris Cedex 15, 91198 Gif sur Yvette Cedex, France
    J Virol 73:6104-10. 1999
    ..These results, together with observations related to the absence of secretion of NS1 from Den-infected insect cells, suggest that maturation and secretion of hexameric NS1 depend on the glycosylation status of the host cell...
  29. pmc Hepatitis C virus p7 and NS2 proteins are essential for production of infectious virus
    Christopher T Jones
    Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    J Virol 81:8374-83. 2007
    ..The protease domain of NS2 was required for infectivity, whereas its catalytic active site was dispensable. We conclude that p7 and NS2 function at an early stage of virion morphogenesis, prior to the assembly of infectious virus...
  30. pmc An antigen capture enzyme-linked immunosorbent assay reveals high levels of the dengue virus protein NS1 in the sera of infected patients
    P R Young
    Sir Albert Sakzewski Virus Research Centre, The Royal Children s Hospital, Herston, Brisbane 4029, Australia
    J Clin Microbiol 38:1053-7. 2000
    ....
  31. ncbi Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial
    Paul Y Kwo
    Department of Medicine, Division of Gastroenterology Hepatology, Indiana University School of Medicine, Indianapolis, IN 46202 5121, USA
    Lancet 376:705-16. 2010
    ..We tested the efficacy of boceprevir, an NS3 hepatitis C virus oral protease inhibitor, when added to peginterferon alfa-2b and ribavirin...
  32. ncbi Mouse neuroinvasive phenotype of West Nile virus strains varies depending upon virus genotype
    David W C Beasley
    Department of Pathology, The University of Texas Medical Branch, Galveston, Texas 77555 0609, USA
    Virology 296:17-23. 2002
    ..Virus isolated in North America was found to be highly neuroinvasive with a lack of age-related resistance to infection in mice normally associated with mosquito-borne flaviviruses...
  33. pmc Hepatitis C virus NS2 protein serves as a scaffold for virus assembly by interacting with both structural and nonstructural proteins
    Yinghong Ma
    Department of Microbiology and Immunology, The University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX 77555 0610, USA
    J Virol 85:86-97. 2011
    ..p7 may play an accessory role by regulating NS2 membrane topology, which is important for NS2-mediated protein interactions and therefore NS2 function...
  34. pmc Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses
    Jorge L Munoz-Jordan
    Department of Microbiology, Box 1124 Mount Sinai School of Medicine, 1 Gustave L Levy Place, New York, New York 10029, USA
    J Virol 79:8004-13. 2005
    ....
  35. pmc Phenotypic characterization of resistant Val36 variants of hepatitis C virus NS3-4A serine protease
    Yi Zhou
    Vertex Pharmaceuticals Incorporated, 130 Waverly Street, Cambridge, MA 02139, USA
    Antimicrob Agents Chemother 52:110-20. 2008
    ..Finally, the sensitivity of these replicon variants to alpha interferon or ribavirin remained unchanged compared to that of the wild-type...
  36. pmc Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity
    Xiao Dong Li
    Howard Hughes Medical Institute, Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Proc Natl Acad Sci U S A 102:17717-22. 2005
    ....
  37. pmc Drug resistance against HCV NS3/4A inhibitors is defined by the balance of substrate recognition versus inhibitor binding
    Keith P Romano
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Proc Natl Acad Sci U S A 107:20986-91. 2010
    ....
  38. pmc The ESEV PDZ-binding motif of the avian influenza A virus NS1 protein protects infected cells from apoptosis by directly targeting Scribble
    Hongbing Liu
    Department of Molecular Biology and Microbiology, Baylor College of Medicine, BCMD 824DB, Houston, TX 77030, USA
    J Virol 84:11164-74. 2010
    ..This study shows that one function of the avian ESEV PBM is to reduce apoptosis during infection through disruption of Scribble's proapoptotic function...
  39. pmc A new influenza virus virulence determinant: the NS1 protein four C-terminal residues modulate pathogenicity
    David Jackson
    Howard Hughes Medical Institute and Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208, USA
    Proc Natl Acad Sci U S A 105:4381-6. 2008
    ..The increase in pathogenicity was not caused by the overproduction of IFN, suggesting the NS1 protein C terminus may interact with PDZ-binding protein(s) and modulate pathogenicity through alternative mechanisms...
  40. pmc The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling
    Maudry Laurent-Rolle
    Laboratory of Virology, Rocky Mountain Laboratories, 903 S Fourth St, Hamilton, MT 59840, USA
    J Virol 84:3503-15. 2010
    ..Thus, a naturally occurring mutation is associated with the function of NS5 in IFN antagonism and may influence virulence of WNV field isolates...
  41. ncbi Tropism of dengue virus in mice and humans defined by viral nonstructural protein 3-specific immunostaining
    Scott J Balsitis
    Division of Infectious Diseases, School of Public Health, and Department of Molecular and Cell Biology, University of California, Berkeley 94720 7354, California, USA
    Am J Trop Med Hyg 80:416-24. 2009
    ..Thus, NS3-specific immunostaining supports roles for infected phagocytes, hepatocytes, and, to a limited degree, endothelial cells in the pathogenesis of severe dengue...
  42. pmc The endoplasmic reticulum provides the membrane platform for biogenesis of the flavivirus replication complex
    Leah K Gillespie
    Department of Microbiology, La Trobe University, Bundoora, Melbourne 3086, Australia
    J Virol 84:10438-47. 2010
    ..In addition, we provide data that indicate that a majority of the viral RNA species housed within the RC is in a double-stranded RNA (dsRNA) form...
  43. ncbi Hepatitis C virus RNA polymerase and NS5A complex with a SNARE-like protein
    H Tu
    Department of Molecular Microbiology and Immunology, University of Southern California School of Medicine, Los Angeles, California 90033, USA
    Virology 263:30-41. 1999
    ..These interactions provide a mechanism for membrane association of the HCV RNA replication complex and further suggest that NS5A is a part of the viral RNA replication complex...
  44. pmc cis- and trans-acting elements in flavivirus RNA replication
    A A Khromykh
    Sir Albert Sakzewski Virus Research Centre, Royal Children s Hospital, Brisbane, Queensland 4029, Australia
    J Virol 74:3253-63. 2000
    ....
  45. ncbi Dengue virus NS5 inhibits interferon-alpha signaling by blocking signal transducer and activator of transcription 2 phosphorylation
    Michela Mazzon
    Department of Infection, University College London Medical School, London, United Kingdom
    J Infect Dis 200:1261-70. 2009
    ..NS5 alone did not, however, induce degradation of STAT2, which occurs when all nonstructural proteins are expressed together. We conclude that DENV NS5 is a potent and specific type I IFN antagonist...
  46. pmc Cellular transcriptional profiling in influenza A virus-infected lung epithelial cells: the role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic influenza
    Gary K Geiss
    Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 99:10736-41. 2002
    ....
  47. pmc Inhibition of the type I interferon response in human dendritic cells by dengue virus infection requires a catalytically active NS2B3 complex
    Juan R Rodriguez-Madoz
    Department of Microbiology, Mount Sinai School of Medicine, One Gustave L Levy Place, Box 1124, New York, NY 10029, USA
    J Virol 84:9760-74. 2010
    ..These results provide a new mechanism by which DENV evades the immune system in humans...
  48. ncbi Characterization of the hepatitis C virus RNA replication complex associated with lipid rafts
    Hideki Aizaki
    Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA
    Virology 324:450-61. 2004
    ..Depletion of cellular cholesterol selectively reduced HCV RNA replication. These findings provide further insights into the mechanism of HCV replication in vivo...
  49. pmc An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization
    Marie Pierre Egloff
    Architecture et Fonction des Macromolecules Biologiques, UMR 6098 CNRS et Université Aix Marseille I et II, ESIL, Campus de Luminy, F 13288 Marseille Cedex 09, France
    EMBO J 21:2757-68. 2002
    ..As RNA capping is an essential viral function, these results provide a structural basis for the rational design of drugs against the emerging flaviviruses...
  50. ncbi Association of amino acid substitution pattern in core protein of hepatitis C virus genotype 1b high viral load and non-virological response to interferon-ribavirin combination therapy
    Norio Akuta
    Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
    Intervirology 48:372-80. 2005
    ..Non-virological responders (NVRs, namely ultimate resistant cases) who do not achieve HCV-RNA negativity during treatment are also encountered. We investigated the pretreatment virological features of NVRs...
  51. pmc Naturally occurring dominant resistance mutations to hepatitis C virus protease and polymerase inhibitors in treatment-naïve patients
    Thomas Kuntzen
    Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Hepatology 48:1769-78. 2008
    ..Viral loads were high in the majority of these patients, suggesting that drug-resistant viral strains might achieve replication levels comparable to nonresistant viruses in vivo...
  52. ncbi Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs
    M E Nemeroff
    Department of Molecular Biology and Biochemistry Rutgers University Piscataway, New Jersey 08854, USA
    Mol Cell 1:991-1000. 1998
    ..Via this novel regulation of pre-mRNA 3' end processing, the NS1 protein selectively inhibits the nuclear export of cellular, and not viral, mRNAs...
  53. ncbi North American and European porcine reproductive and respiratory syndrome viruses differ in non-structural protein coding regions
    R Allende
    Department of Veterinary and Biomedical Sciences, University of Nebraska Lincoln, 68583 0905, USA
    J Gen Virol 80:307-15. 1999
    ..The 3' NCR (150 nucleotides) was 76% identical between isolates. These genomic differences confirm the presence of distinct North American and European PRRSV genotypes...
  54. ncbi Newly synthesized dengue-2 virus nonstructural protein NS1 is a soluble protein but becomes partially hydrophobic and membrane-associated after dimerization
    G Winkler
    Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School, University of Medicine and Dentistry, Piscataway, New Jersey 08854 5635
    Virology 171:302-5. 1989
    ..In experiments in which infected cells were treated with tunicamycin it was shown that the glycosylation of NS1 was not required for either the dimerization or the membrane association...
  55. pmc The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein
    Zsuzsanna T Varga
    Department of Microbiology, Mount Sinai School of Medicine, New York City, New York, United States of America
    PLoS Pathog 7:e1002067. 2011
    ..In summary, we have characterized the anti-interferon function of PB1-F2 and we suggest that this activity contributes to the enhanced pathogenicity seen with PB1-F2 N66S- expressing influenza viruses...
  56. ncbi Transient structure and SH3 interaction sites in an intrinsically disordered fragment of the hepatitis C virus protein NS5A
    Sophie Feuerstein
    Institut de Biologie Structurale, Université Grenoble 1, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France
    J Mol Biol 420:310-23. 2012
    ..The present work also highlights the power of NMR spectroscopy to characterize multiple binding events including short-lived transient interactions between globular and highly disordered proteins...
  57. pmc Hepatitis C virus variants with decreased sensitivity to direct-acting antivirals (DAAs) were rarely observed in DAA-naive patients prior to treatment
    Doug J Bartels
    Vertex Pharmaceuticals, Inc, Department of Infectious Diseases, Cambridge, Massachusetts, USA
    J Virol 87:1544-53. 2013
    ..The effect of specific resistant variant frequency on response to various DAA treatments in different patient populations, including interferon nonresponders, should be further studied...
  58. pmc Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons
    Rainer Gosert
    Department of Medicine II, University of Freiburg, Germany
    J Virol 77:5487-92. 2003
    ..Metabolic labeling with 5-bromouridine 5'-triphosphate in the presence of actinomycin D revealed that the membranous web is the site of viral RNA synthesis and therefore represents the replication complex of HCV...
  59. ncbi A single nucleotide mutation in NS2A of Japanese encephalitis-live vaccine virus (SA14-14-2) ablates NS1' formation and contributes to attenuation
    Qing Ye
    Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China
    J Gen Virol 93:1959-64. 2012
    ..These findings provide critical information in understanding the molecular mechanism of JE vaccine attenuation and is critical for JE vaccine quality control...
  60. pmc Identification of RNA helicase A as a cellular factor that interacts with influenza A virus NS1 protein and its role in the virus life cycle
    Li Lin
    Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
    J Virol 86:1942-54. 2012
    ..In summary, we established a system to identify cellular factors that interact with NS1 protein during virus infection and furthermore demonstrated that RHA interacts with NS1 and enhances viral replication and transcription...
  61. pmc Comparison of the diagnostic accuracy of commercial NS1-based diagnostic tests for early dengue infection
    Lyda Osorio
    Grupo de Epidemiologia y Salud Poblacional GESP Escuela de Salud Publica, Facultad de Salud, Universidad del Valle, Cali, Colombia Calle 4b 36 140, Cali Colombia
    Virol J 7:361. 2010
    ..We compared the diagnostic accuracy and reproducibility of commercially available NS1-based dengue tests and explored factors influencing their sensitivities...
  62. pmc A major determinant of cyclophilin dependence and cyclosporine susceptibility of hepatitis C virus identified by a genetic approach
    Feng Yang
    Department of Biological Science, Florida State University, Tallahassee, Florida, United States of America
    PLoS Pathog 6:e1001118. 2010
    ..This study describes a new genetic approach to identifying viral targets of cellular cofactors and identifies a major regulator of HCV's susceptibility to CsA and its derivatives that are currently in clinical trials...
  63. pmc In vitro resistance profile of the hepatitis C virus NS3/4A protease inhibitor TMC435
    Oliver Lenz
    Tibotec BVBA, Mechelen, Belgium
    Antimicrob Agents Chemother 54:1878-87. 2010
    ..Finally, combinations of TMC435 with alpha interferon and NS5B polymerase inhibitors prevented the formation of drug-resistant replicon colonies...
  64. pmc Role of annexin A2 in the production of infectious hepatitis C virus particles
    Perdita Backes
    Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany
    J Virol 84:5775-89. 2010
    ..ANXA2 colocalized with viral nonstructural proteins in cells harboring genotype 1 or 2 replicons as well as in infected cells...
  65. pmc Role of oxysterol binding protein in hepatitis C virus infection
    Yutaka Amako
    Department of Medicine, University of California, San Diego, La Jolla, 92093, USA
    J Virol 83:9237-46. 2009
    ..OSBP deletion mutation in the PH (DeltaPH) domain failed to localize to the Golgi apparatus and inhibited the HCV particle release. These studies suggest a possible functional role of OSBP in the HCV maturation process...
  66. pmc Genetic history of hepatitis C virus in East Asia
    Oliver G Pybus
    Department of Zoology, University of Oxford, Oxford, United Kingdom
    J Virol 83:1071-82. 2009
    ..Our analysis explains the generation and maintenance of HCV diversity in Asia and could provide a template for further investigations of HCV spread in other regions...
  67. pmc Binding of flavivirus nonstructural protein NS1 to C4b binding protein modulates complement activation
    Panisadee Avirutnan
    Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 187:424-33. 2011
    ..Together, these studies further define the immune evasion potential of NS1 in reducing the functional capacity of C4 in complement activation and control of flavivirus infection...
  68. pmc Interaction of hepatitis C virus nonstructural protein 5A with core protein is critical for the production of infectious virus particles
    Takahiro Masaki
    Department of Virology II, National Institute of Infectious Diseases, 1 23 1 Toyama, Shinjuku ku, Tokyo 162 8640, Japan
    J Virol 82:7964-76. 2008
    ..These results suggest that NS5A plays a key role in regulating the early phase of HCV particle formation by interacting with core protein and that its C-terminal serine cluster is a determinant of the NS5A-core interaction...
  69. ncbi Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A
    Francois Penin
    Institut de Biologie et Chimie des Proteines, CNRS UMR 5086, IFR128 BioSciences, Lyon Gerland, Lyon F 69367, Cedex 07, France
    J Biol Chem 279:40835-43. 2004
    ....
  70. ncbi Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by either PACT or double-stranded RNA
    Shoudong Li
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Virology 349:13-21. 2006
    ..In addition, we demonstrated that PKR activation is inhibited in cells infected with a recombinant influenza A virus expressing NS1A mutant protein that cannot bind RNA, as is the case in cells infected with wild-type influenza A virus...
  71. pmc Genetic determinants of virulence in pathogenic lineage 2 West Nile virus strains
    Elizabeth M Botha
    University of Pretoria, Pretoria, South Africa
    Emerg Infect Dis 14:222-30. 2008
    ..Major deletions existed in the 3 noncoding region of 2 lineage 2 strains previously shown to be either less or not neuroinvasive relative to the highly neuroinvasive strains sequenced in this study...
  72. pmc Phosphorylation of hepatitis C virus nonstructural protein 5A modulates its protein interactions and viral RNA replication
    Matthew J Evans
    Integrated Program in Cellular, Molecular, and Biophysical Studies, Department of Biochemistry and Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 101:13038-43. 2004
    ....
  73. pmc Blocking of interferon-induced Jak-Stat signaling by Japanese encephalitis virus NS5 through a protein tyrosine phosphatase-mediated mechanism
    Ren Jye Lin
    Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 11529, Taiwan, Republic of China
    J Virol 80:5908-18. 2006
    ..We suggest that JEV NS5 is an IFN antagonist and that it may play a role in blocking IFN-stimulated Jak-Stat signaling via activation of PTPs during JEV infection...
  74. pmc NS5 of dengue virus mediates STAT2 binding and degradation
    Joseph Ashour
    Department of Microbiology, Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Virol 83:5408-18. 2009
    ..Therefore, we have identified both a novel mechanism by which DENV evades the innate immune response and a potential target for antiviral therapeutics...
  75. pmc Comparison of two commercially available dengue virus (DENV) NS1 capture enzyme-linked immunosorbent assays using a single clinical sample for diagnosis of acute DENV infection
    Kovi Bessoff
    Centers for Disease Control and Prevention, Division of Vector Borne Infectious Diseases, Dengue Branch, SanJuan, Puerto Rico 00920
    Clin Vaccine Immunol 15:1513-8. 2008
    ..We concluded that the NS1 capture ELISA is a useful tool that can improve testing algorithms to diagnose DENV infection in single samples from acute and early convalescent cases...
  76. pmc Interaction of the influenza virus nucleoprotein with the cellular CRM1-mediated nuclear export pathway
    D Elton
    Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom
    J Virol 75:408-19. 2001
    ..Consistent with this, NP bound CRM1 in vitro. Overall, these data raise the possibility that RNP export is mediated by a direct interaction between NP and the cellular CRM1 export pathway...
  77. pmc Structure and functionality in flavivirus NS-proteins: perspectives for drug design
    Michela Bollati
    Department of Biomolecular Sciences and Biotechnology, University of Milano, Via Celoria 26, 20133 Milano, Italy
    Antiviral Res 87:125-48. 2010
    ..The ultimate aim of the reported approaches is to shed light on the design and development of antiviral drug leads...
  78. ncbi The unique architecture of Bunyamwera virus factories around the Golgi complex
    Juan Fontana
    Cell Structure Laboratory, Centro Nacional de Biotecnologia, CSIC, Campus Universidad Autonoma, Cantoblanco, 28049 Madrid, Spain
    Cell Microbiol 10:2012-28. 2008
    ....
  79. ncbi A site on the influenza A virus NS1 protein mediates both inhibition of PKR activation and temporal regulation of viral RNA synthesis
    Ji Young Min
    Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, room 2 122, 2500 Speedway, University of Texas at Austin, Austin, TX 78712, USA
    Virology 363:236-43. 2007
    ..This interaction would occur in the nucleus, whereas PKR would bind to NS1A proteins in the cytoplasm prior to their import into the nucleus...
  80. pmc The hepatitis C virus NS4B protein can trans-complement viral RNA replication and modulates production of infectious virus
    Daniel M Jones
    MRC Virology Unit, Church Street, Glasgow G11 5JR, United Kingdom
    J Virol 83:2163-77. 2009
    ..Finally, one of the NS4B mutations increased the yield of infectious virus by five- to sixfold. Hence, NS4B not only functions in RNA replication but also contributes to the processes engaged in virus assembly and release...
  81. pmc Antagonism of the complement component C4 by flavivirus nonstructural protein NS1
    Panisadee Avirutnan
    Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    J Exp Med 207:793-806. 2010
    ..Through this mechanism, NS1 protects DENV from complement-dependent neutralization in solution. These studies define a novel immune evasion mechanism for restricting complement control of microbial infection...
  82. pmc Influenza A virus polymerase inhibits type I interferon induction by binding to interferon beta promoter stimulator 1
    Atsushi Iwai
    Department of Bioresources, hHokkaido University Research Center for Zoonosis Control, North 20, West 10 Kita ku, Sapporo, Hokkaido 001 0020, Japan
    J Biol Chem 285:32064-74. 2010
    ..These findings demonstrate that the viral polymerase plays an important role for regulating host anti-viral response through the binding to IPS-1 and inhibition of IFNβ production...
  83. pmc Alpha interferon induces distinct translational control programs to suppress hepatitis C virus RNA replication
    Chunfu Wang
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9048, USA
    J Virol 77:3898-912. 2003
    ..We conclude that IFN blocks HCV replication through translational control programs involving PKR and P56 to, respectively, target eIF2- and eIF3-dependent steps in the viral RNA translation initiation process...
  84. pmc Influenza A virus NS1 protein binds p85beta and activates phosphatidylinositol-3-kinase signaling
    Benjamin G Hale
    Centre for Biomolecular Sciences, University of St Andrews, St Andrews, Fife KY16 9ST, United Kingdom
    Proc Natl Acad Sci U S A 103:14194-9. 2006
    ..These data suggest that activation of PI3K signaling in influenza A virus-infected cells is important for efficient virus replication...
  85. pmc Mutation analysis of a recombinant NS replicon shows that influenza virus NS1 protein blocks the splicing and nucleo-cytoplasmic transport of its own viral mRNA
    Urtzi Garaigorta
    Centro Nacional de Biotecnologia CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain
    Nucleic Acids Res 35:4573-82. 2007
    ..These results rule out previous models to explain the regulation of mRNA processing and transport by NS1 and underlines the relevance of NS1 protein in the control of virus gene expression...
  86. pmc Ultrastructure of Kunjin virus-infected cells: colocalization of NS1 and NS3 with double-stranded RNA, and of NS2B with NS3, in virus-induced membrane structures
    E G Westaway
    Sir Albert Sakzewski Virus Research Centre, Royal Children s Hospital, Brisbane, Australia
    J Virol 71:6650-61. 1997
    ..The collection of induced membranes may represent virus factories in which translation, RNA synthesis, and virus assembly occur...
  87. pmc Infection and transmission of Rift Valley fever viruses lacking the NSs and/or NSm genes in mosquitoes: potential role for NSm in mosquito infection
    Mary B Crabtree
    Division of Vector Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, United States of America
    PLoS Negl Trop Dis 6:e1639. 2012
    ....
  88. pmc The H5N1 influenza virus NS genes selected after 1998 enhance virus replication in mammalian cells
    Karen Y Twu
    Institute for Cellular and Molecular Biology, University of Texas at Austin, 2500 Speedway, Austin, TX 78712, USA
    J Virol 81:8112-21. 2007
    ..Consequently, these internal HK97 proteins largely compensate for the absence of F103 and M106, presumably by stabilizing the NS1A-CPSF30 complex...
  89. ncbi Domain 2 of nonstructural protein 5A (NS5A) of hepatitis C virus is natively unfolded
    Yu Liang
    Division of Structural and Computational Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637511, Singapore
    Biochemistry 46:11550-8. 2007
    ....
  90. pmc Crystal structure of a novel dimeric form of NS5A domain I protein from hepatitis C virus
    Robert A Love
    Structural Biology Group, Pfizer Global Research and Development, La Jolla Laboratories, San Diego, California 92121, USA
    J Virol 83:4395-403. 2009
    ..The two alternate structural forms of domain I now available may be indicative of the multiple roles emerging for NS5A in viral RNA replication and viral particle assembly...
  91. ncbi Genetic diversity and evolution of hepatitis C virus--15 years on
    Peter Simmonds
    Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, UK
    J Gen Virol 85:3173-88. 2004
    ..These contrasting aspects of conservatism and adaptability provide a fascinating paradigm in which to explore the complex selection pressures that underlie the evolution of HCV and other persistent viruses...
  92. pmc Metabolism of phosphatidylinositol 4-kinase IIIα-dependent PI4P Is subverted by HCV and is targeted by a 4-anilino quinazoline with antiviral activity
    Annalisa Bianco
    Department of Genomics and Molecular Biology, Virology Program, Istituto Nazionale Genetica Molecolare INGM, Milano, Italy
    PLoS Pathog 8:e1002576. 2012
    ..This observation implies that HCV--by recruiting PI4KIIIα in the RNA replication complex--hijacks PI4P metabolism, ultimately resulting in a markedly altered subcellular distribution of the PI4KIIIα product...
  93. pmc Functional investigation of grass carp reovirus nonstructural protein NS80
    Lin Cai
    State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
    Virol J 8:168. 2011
    ..It has been suggested that the protein NS80 plays an important role in the viral replication cycle that is similar to that of its homologous protein μNS in the genus of Orthoreovirus...
  94. pmc NSs protein of rift valley fever virus promotes posttranslational downregulation of the TFIIH subunit p62
    Birte Kalveram
    Department of Pathology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 0438, USA
    J Virol 85:6234-43. 2011
    ..These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus...
  95. pmc Structural and functional characterization of nonstructural protein 2 for its role in hepatitis C virus assembly
    Vlastimil Jirasko
    Department of Molecular Virology, University of Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany
    J Biol Chem 283:28546-62. 2008
    ..Finally, we demonstrate that mutations in NS2 blocking HCV assembly can be rescued by trans-complementation...
  96. pmc Species-specific contribution of the four C-terminal amino acids of influenza A virus NS1 protein to virulence
    Sébastien M Soubies
    INRA, UMR 1225, Ecole Nationale Veterinaire de Toulouse, F 31076 Toulouse, France
    J Virol 84:6733-47. 2010
    ..H7N1 virus with a C-terminal RSKV motif replicated to higher levels in ducks and induced higher levels of Mx, a type I interferon-stimulated gene. Thus, we identify the C-terminal domain of NS1 as a species-specific virulence domain...
  97. pmc Clinical and virological features of Dengue in Vietnamese infants
    Tran Nguyen Bich Chau
    Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
    PLoS Negl Trop Dis 4:e657. 2010
    ..The clinical and laboratory features in infants with dengue have not been extensively characterised...
  98. pmc Structural and functional studies of nonstructural protein 2 of the hepatitis C virus reveal its key role as organizer of virion assembly
    Vlastimil Jirasko
    Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Heidelberg, Germany
    PLoS Pathog 6:e1001233. 2010
    ..In conclusion, our results suggest that NS2 orchestrates HCV particle formation by participation in multiple protein-protein interactions required for their recruitment to assembly sites in close proximity of LDs...
  99. pmc The NS1 gene contributes to the virulence of H5N1 avian influenza viruses
    Zejun Li
    Harbin Veterinary Research Institute, CAAS, 427 Maduan Street, Harbin 150001, People s Republic of China
    J Virol 80:11115-23. 2006
    ....
  100. pmc The hepatitis C virus NS3 protein: a model RNA helicase and potential drug target
    David N Frick
    Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA
    Curr Issues Mol Biol 9:1-20. 2007
    ....
  101. ncbi Silibinin and related compounds are direct inhibitors of hepatitis C virus RNA-dependent RNA polymerase
    Abdelhakim Ahmed-Belkacem
    Research Team Pathophysiology and Therapy of Chronic Viral Hepatitis, INSERM U955, Creteil, France
    Gastroenterology 138:1112-22. 2010
    ..The aim of this study was to test the principal isomers contained in silymarin preparations for their ability to inhibit HCV enzymatic functions and replication in different models...

Research Grants62

  1. MOLECULAR BASIS OF REOVIRUS PATHOGENESIS
    Terence S Dermody; Fiscal Year: 2013
    ..abstract_text> ..
  2. A quantitative proteomics approach to understand viral immune evasion strategies
    Michele E Hardy; Fiscal Year: 2010
    ..Understanding these pathways and the mechanisms by which viruses evade the innate immune response may lead new approaches to attenuated vaccines or antiviral drug targets specifically designed to bypass viral evasion strategies. ..
  3. C5a as an Anti-HIV Microbicidal Candidate
    PHILIPPE ANDRE GALLAY; Fiscal Year: 2013
    ..In addition, protective results would provide proof-of-concept of the usefulness of topically applied microbicides, such as C5A, to prevent genital HIV transmission. ..
  4. Determinants of Coronavirus Fidelity in Replication and Pathogenesis
    Mark R Denison; Fiscal Year: 2013
    ..The results of the proposed experiments will identify fidelity determinants critical for replication, pathogenesis and virulence, define the range of tolerated fidelity, and identify novel approaches for CoV attenuation and inhibition. ..
  5. GB Virus C and Non-Hodgkins Lymphoma Risk and Prognosis
    Jack T Stapleton; Fiscal Year: 2013
    ..Regardless of the results obtained, this study has the potential to have a great impact on public health regarding transfusion medicine, and potentially in the clinical management of NHL patients. ..
  6. Development of Nanotherapeutics for RSV-induced Lung Disease
    Shyam S Mohapatra; Fiscal Year: 2013
    ..The results are expected to lead to the discovery of novel targets and to the initiation of preclinical studies of these targets against RSV lung disease. ..
  7. Rational Development of Candidate Attenuated Flavivirus Vaccines
    Tian Wang; Fiscal Year: 2013
    ....
  8. Astrovirus structure and replication
    Yizhi Jane Tao; Fiscal Year: 2013
    ..The structure of the complex will reveal whether the same catalytic mechanism is used for both VPg nucleotidylation and regular nucleotide polymerization. ..
  9. Enteric Virus Calcium Channel Inhibitors
    Joseph M Hyser; Fiscal Year: 2013
    ....
  10. Genotyping and Phenotyping the Hepatitis C Drug Target NS5A
    ROBERT T STRIKER; Fiscal Year: 2011
    ..This database will catalog VA strains of HCV that need to be targeted by antivirals like cyclophilin inhibitors as well as others that are currently being investigated mostly outside the VA. ..
  11. Immune Mechanisms of HCV Persistence and Pathogenesis
    Jiaren Sun; Fiscal Year: 2012
    ..abstract_text> ..
  12. Viral Protein Determinants of Coronavirus Replication Fidelity
    Everett Clinton Smith; Fiscal Year: 2013
    ..Additionally, given the high conservation of nsp14-ExoN within coronaviruses, ExoN inhibitors would represent a novel class of antivirals with potential pan-coronavirus activity. ..
  13. Dendritic Cell Targeting Enhances Flavivirus Vaccine Efficacy
    Gregg Milligan; Fiscal Year: 2009
    ..These studies will provide important insights into links between innate and adaptive immunity that lead to the production of protective immunity to flavivirus infection and vaccination. ..
  14. Immune Evasion Mechanisms of Neurovirulent Alphaviruses
    Mark T Heise; Fiscal Year: 2012
    ..Therefore, studies are proposed to 1) characterize the mechanism(s) by which the viral nonstructural proteins antagonize RIG- I function, 2) determine whether other steps in the type I IFN induction pathway are ..
  15. Viral and Cellular Determinants of HCV Assembly
    GUANGXIANG GEORGE LUO; Fiscal Year: 2013
    ..Our studies will also provide novel targets for discovery of antiviral drugs to effectively treat hepatitis C. ..
  16. Mechanisms and Functions of Core-induced Lipid Droplet Accumulation in Hepatitis
    MELANIE MARIA OTT; Fiscal Year: 2010
    ..These studies are directly relevant to HCV pathogenesis and may contribute to the development of novel antiviral drugs that will address public need. ..
  17. Antivirals for Hepatitis C Targeting Phosphoinositide Metabolism
    Michael A Gelman; Fiscal Year: 2013
    ..We will also use these compounds to investigate how HCV makes copies of itself and how this process depends on the activity of PI4K. ..
  18. Molecular determinants of hepatitis C virus assembly
    Brett D Lindenbach; Fiscal Year: 2013
    ..Our studies characterize the virus particle assembly process, which will provide new avenues to target HCV and thereby prevent or treat disease. ..
  19. Alphavirus Modulation of the Host Type I Interferon System
    Catherine Cruz; Fiscal Year: 2010
    ....
  20. Cyclophilins, Cyclophilin Inhibitors and Hepatitis C
    PHILIPPE ANDRE GALLAY; Fiscal Year: 2013
    ..The study of the roles of Cyp - the intracellular targets of the Cyp inhibitors - in HCV replication is novel and should lead to the identification of new host and viral targets for the development of innovative anti-HCV therapies. ..
  21. Inhibition of the Interferon Response by West Nile Virus
    Christoph Seeger; Fiscal Year: 2010
    ..The studies proposed here will provide a better understanding of host-virus interactions that control WNV replication and pathogenesis. This new information can be used as the basis for the development of effective antiviral therapies. ..
  22. Regulation of host cell gene expression by the hepatitis C virus protein NS5A
    JOSE DANIEL DEBES; Fiscal Year: 2013
    ..abstract_text> ..
  23. HIV TAT protein in nicotine dependence
    Svetlana Semenova; Fiscal Year: 2013
    ..Understanding the effects of TAT expression may help identify a target for development of preventative or adjunct therapies for the treatment of nicotine dependence in the HIV-infected population. ..
  24. STRUCTURAL STUDIES OF ROTAVIRUSES
    BIDADI VENKATARAM PRASAD; Fiscal Year: 2013
    ..Our structural studies may provide insight into manipulation of the NSP1 gene to design a rationally attenuated, second-generation RV vaccine. ..
  25. Sindbis nonstructural protein nsP2: Interaction with cellular proteins
    Elena I Frolova; Fiscal Year: 2012
    ..on the basis of our preliminary data, that SINV nsP2 plays critical roles not only in the processing of viral nonstructural proteins and synthesis of virus-specific RNAs, but also in controlling the development of the virus-induced ..
  26. STRUCTURES OF RNA BINDING PROTEINS FROM INFLUENZA VIRUS
    Gaetano Montelione; Fiscal Year: 2000
    ..These analogs will have great significance both in fundamental studies as well as in treating (or in developing drugs for) obesity, hypertension and failing heart. ..
  27. Mechanisms of Reovirus Bloodstream Dissemination
    Karl W Boehme; Fiscal Year: 2013
    ..Such insights might lead to new treatments for degenerative, immunologic, or neoplastic diseases. ..
  28. Host factors in the alphavirus replication complex
    Margaret MacDonald; Fiscal Year: 2009
    ..of incoming positive-sense genomic RNA, which occurs in membrane-associated complexes containing the viral nonstructural proteins (nsPs), first generates a minus strand copy, followed by new progeny plus strand RNAs...
  29. Rationally designed Rift Valley Fever Virus Vaccine
    Ramon Flick; Fiscal Year: 2009
    ..A vaccine would be extremely useful in future eradication programs by reducing infection in cattle, sheep and humans, and reducing the social, economic, and environmental impact of the disease. ..
  30. Structural and Functional Studies of Hepatitic C Core and NS4B Proteins
    Daniel Calarese; Fiscal Year: 2009
    ..Understanding the precise role of these proteins in the virus life cycle would not only advance knowledge in basic HCV biology, but would illuminate novel targets for therapeutic drug design. ..
  31. Activation of innate antiviral defenses by LTbetaR
    CHRISTOPHER BENEDICT; Fiscal Year: 2005
    ..abstract_text> ..
  32. VIRUS/HOST INTERACTIONS MODULATED BY HEPATITIC C VIRUS
    Radhakrishnan Padmanabhan; Fiscal Year: 2001
    ..abstract_text> ..
  33. Dendritic cell targeted hepatitis c virus immunotherapy
    Tyler Curiel; Fiscal Year: 2003
    ..that express and secrete DC-targeted NS3. A needle-less and non-toxic immunotherapy would provide a treatment for hepatitis C patients who currently have none. ..
  34. ARBOVIRUS REPLICATION IN MOSQUITO AND VERTEBRATE CELLS
    Victor Stollar; Fiscal Year: 1991
    ..What we learn from these studies concerning the SV genome and its replication strategy may ultimately lead to novel strategies for the control of medically important viruses, which are transmitted by arthropod vectors...
  35. Interaction of Sindbis Virus with Cellular Processes
    Ilya Frolov; Fiscal Year: 2002
    ..abstract_text> ..
  36. Genetic Analysis of Papillomavirus Virion Morphogenesis
    Craig Meyers; Fiscal Year: 2009
    ..PV) have evolved functional domains for the proper interaction between themselves, with PV viral nonstructural proteins, with PV genomic DNA, and with host cell factors, allowing for morphogenesis of infectious viral ..
  37. MOLECULAR BIOLOGY OF THE ROTAVIRUSES
    MARY ESTES; Fiscal Year: 2005
    ....
  38. Characterization of the HCV p7 Protein
    Christopher Jones; Fiscal Year: 2009
    ..In addition, I have genetically identified putative interactions between p7 and viral nonstructural proteins including NS2...
  39. Viral Inhibition of Interferon Effects in the Airway
    Murali Ramaswamy; Fiscal Year: 2007
    ..is that RSV induces proteasome-dependent degradation of Stat2, and this effect is mediated by specific viral nonstructural proteins. The overall goal of this proposal is to investigate the biochemical basis for RSV effects on antiviral ..
  40. HIV-1 Infection Increases Brain Amyloid Beta
    Lynn Pulliam; Fiscal Year: 2006
    ..We believe that mechanisms derived from these experiments will have implications for long term survivors of HIV-1 infection and hopefully give us new clues for therapeutic strategies against HIV-associated dementia. ..
  41. Novel Strategy for HCV NS3 Inhibitor Discovery
    Steven Ogata; Fiscal Year: 2001
    ..Market analysis estimates that the value of such drugs has potential for producing more than a billion-dollar per year income. ..
  42. Identification of Hepatitis C Virus Replication Complex
    Guangxiang Luo; Fiscal Year: 2003
    ..suggests that HCV RNA genome is likely replicated in a membrane-bound protein complex consisting of viral nonstructural proteins and probably also cellular proteins...
  43. Densoviruses as Transducing Vectors
    Jonathan Carlson; Fiscal Year: 2001
    ..In the second specific aim, the constraints to the variability and compatibility of viral nonstructural proteins, terminal inverted repeats and the noncoding region just inside the right end will be investigated...
  44. Densoviruses as Transducing Vectors
    Jonathan Carlson; Fiscal Year: 2005
    ..In the second Specific Aim, the constraints to the variability and compatibility of viral nonstructural proteins, terminal inverted repeats and the noncoding region just inside the right end will be investigated...
  45. Cellular Protein Interactions with Viral Inhibitors
    MARK CHUA; Fiscal Year: 2005
    ..This proposal outlines the identification and characterization of the cellular proteins that VP35 and NS 1 interacts with. ..
  46. Enzymatic Differences Among Hepatitis C Virus Genotypes
    David Frick; Fiscal Year: 2007
    ..abstract_text> ..
  47. Hepatitis C VIrus NS3 Helicase Inhibitor Discovery
    David Frick; Fiscal Year: 2008
    ..The goal here is to find chemicals that prevent the virus from replicating in human cells. [unreadable] [unreadable] [unreadable]..
  48. Development of Novel Antiviral Agents VS West Nile Virus
    Michael Diamond; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  49. INTERFERON IN MODULATING DENGUE VIRUS INFECTION
    Michael Diamond; Fiscal Year: 2002
    ....
  50. Extrahepatic Replication and Viral Evolution of HCV During HCV/HIV Co-infection
    Jason Blackard; Fiscal Year: 2007
    ..This proposal will provide important data on co-factors of virus transmission and identify potential markers of HCV disease progression and treatment failure. [unreadable] [unreadable] [unreadable]..
  51. Improved Vaccines for Rift Valley Fever Virus
    Mark T Heise; Fiscal Year: 2010
    ....
  52. Defining NS4B Function in Hepatitis C Virus Replication
    Keril J Blight; Fiscal Year: 2010
    ..abstract_text> ..
  53. Oas-1 gene transgenic mice for WNV research.
    MARGO BRINTON; Fiscal Year: 2005
    ....
  54. Modification of Conserved Influenza Genes Enabling their Elevated Expression
    Petr Ilyinskii; Fiscal Year: 2008
    ..Therefore, if proven, our approach will lead to a novel paradigm for recombinant gene modifications for enhanced expression in vivo, both for vaccine and non-vaccine applications. [unreadable] [unreadable] [unreadable]..
  55. EFFECTORS AND IINHIBITORS OF SARS VIRUS POLYMERASE
    Neerja Kaushik Basu; Fiscal Year: 2006
    ..Further, analysis of the sensitivity of the SARS-CoV RdRp towards a panel of known and novel inhibitors of polymerases will provide new leads in the quest for specific antiviral agents against the SARS-CoV RdRp. ..
  56. Development of a new model of viral hemorrhagic fever.
    MARGO BRINTON; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  57. Analysis of SNPs Associated With WNV-Induced Disease
    MARGO BRINTON; Fiscal Year: 2006
    ..Further analyses will include fine mapping and sequencing of the causative mutation(s). ..
  58. Molecular Modulators of HCV Replication
    Neerja Kaushik Basu; Fiscal Year: 2007
    ..This will enable us to understand, at the molecular level, the replication process of hepatitis C virus and will further facilitate the development of effective drugs/inhibitors against HCV. ..
  59. Functional analysis of flavivirus genetic resistance.
    Margo A Brinton; Fiscal Year: 2010
    ..This research is relevant to understanding individual variation in the response to flavivirus infections among humans. ..
  60. SELECTIVE INHIBITION OF HCV TRANSLATION BY TETRAPEPTIDE
    ALEXANDER BIRK; Fiscal Year: 2008
    ..If DAPL or related analogues can be further developed to target and inhibit HCV RNA translation, the clinical application of this kind of therapeutics might be significant. ..
  61. TOGAVIRUS TROPISM FOR BONES, JOINTS, AND CNS
    Mark T Heise; Fiscal Year: 2010
    ....
  62. Novel broad spectrum vaccination against influenza
    Petr Ilyinskii; Fiscal Year: 2006
    ..The overall aim of this project is to demonstrate better protective effect or/and enhanced immune response using modified influenza proteins as immunogens compared to wild-type viral proteins. ..