HCVgp1

Summary

Gene Symbol: HCVgp1
Description: polyprotein
Species: Hepatitis C virus

Top Publications

  1. pmc Polo-like kinase 1 is involved in hepatitis C virus replication by hyperphosphorylating NS5A
    Yung Chia Chen
    Institute of Microbiology and Immunology, National Yang Ming University, Taipei 112, Taiwan
    J Virol 84:7983-93. 2010
  2. pmc Trans-complementation of an NS2 defect in a late step in hepatitis C virus (HCV) particle assembly and maturation
    Minkyung Yi
    Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX, USA
    PLoS Pathog 5:e1000403. 2009
  3. ncbi Hepatitis C virus (HCV) NS5A binds RNA-dependent RNA polymerase (RdRP) NS5B and modulates RNA-dependent RNA polymerase activity
    Yukihiro Shirota
    Department of Molecular Oncology, Kanazawa University, 13 1 Takara machi, Kanazawa 920 0934, Ishikawa, Japan
    J Biol Chem 277:11149-55. 2002
  4. pmc Alanine scanning of the hepatitis C virus core protein reveals numerous residues essential for production of infectious virus
    Catherine L Murray
    Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Ave, New York, NY 10021, USA
    J Virol 81:10220-31. 2007
  5. pmc Interactions between viral nonstructural proteins and host protein hVAP-33 mediate the formation of hepatitis C virus RNA replication complex on lipid raft
    Lu Gao
    Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA
    J Virol 78:3480-8. 2004
  6. pmc Hypervariable region 1 differentially impacts viability of hepatitis C virus strains of genotypes 1 to 6 and impairs virus neutralization
    Jannick Prentoe
    Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, DK 2650 Hvidovre, Denmark
    J Virol 85:2224-34. 2011
  7. ncbi Phenotypic and structural analyses of hepatitis C virus NS3 protease Arg155 variants: sensitivity to telaprevir (VX-950) and interferon alpha
    Yi Zhou
    Vertex Pharmaceuticals Inc, Cambridge, Massachusetts 02139, USA
    J Biol Chem 282:22619-28. 2007
  8. pmc NS3 helicase domains involved in infectious intracellular hepatitis C virus particle assembly
    Yinghong Ma
    Center for Hepatitis Research, The University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX 77555 1073, USA
    J Virol 82:7624-39. 2008
  9. doi The non-structural 5A protein of hepatitis C virus exhibits genotypic differences in interferon antagonism
    Ya Hui Tsai
    Graduate Institute of Microbiology, National Taiwan University College of Medicine, Taipei 100, Taiwan
    J Hepatol 49:899-907. 2008
  10. doi Compensatory mutations in NS3 and NS5A proteins enhance the virus production capability of hepatitis C reporter virus
    Qingxia Han
    State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People s Republic of China
    Virus Res 145:63-73. 2009

Research Grants

Detail Information

Publications175 found, 100 shown here

  1. pmc Polo-like kinase 1 is involved in hepatitis C virus replication by hyperphosphorylating NS5A
    Yung Chia Chen
    Institute of Microbiology and Immunology, National Yang Ming University, Taipei 112, Taiwan
    J Virol 84:7983-93. 2010
    ..Because of the differential effects of Plk1 on HCV replication and host cell growth, Plk1 could potentially serve as a target for anti-HCV therapy...
  2. pmc Trans-complementation of an NS2 defect in a late step in hepatitis C virus (HCV) particle assembly and maturation
    Minkyung Yi
    Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX, USA
    PLoS Pathog 5:e1000403. 2009
    ..In aggregate, these results indicate that NS2 functions in trans, in a late-post assembly maturation step, perhaps in concert with NS5A, to confer infectivity to the HCV particle...
  3. ncbi Hepatitis C virus (HCV) NS5A binds RNA-dependent RNA polymerase (RdRP) NS5B and modulates RNA-dependent RNA polymerase activity
    Yukihiro Shirota
    Department of Molecular Oncology, Kanazawa University, 13 1 Takara machi, Kanazawa 920 0934, Ishikawa, Japan
    J Biol Chem 277:11149-55. 2002
    ..Taken together, our results support the idea that NS5A modulates HCV replication as a component of replication complex...
  4. pmc Alanine scanning of the hepatitis C virus core protein reveals numerous residues essential for production of infectious virus
    Catherine L Murray
    Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Ave, New York, NY 10021, USA
    J Virol 81:10220-31. 2007
    ....
  5. pmc Interactions between viral nonstructural proteins and host protein hVAP-33 mediate the formation of hepatitis C virus RNA replication complex on lipid raft
    Lu Gao
    Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA
    J Virol 78:3480-8. 2004
    ..These results indicate that protein-protein interactions among the various HCV NS proteins and hVAP-33 are important for the formation of HCV replication complex...
  6. pmc Hypervariable region 1 differentially impacts viability of hepatitis C virus strains of genotypes 1 to 6 and impairs virus neutralization
    Jannick Prentoe
    Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, DK 2650 Hvidovre, Denmark
    J Virol 85:2224-34. 2011
    ..Only the 2a virus displayed such a correlation. Our findings indicate that HVR1 of HCV shields important conserved neutralization epitopes with implications for viral persistence, immunotherapy, and vaccine development...
  7. ncbi Phenotypic and structural analyses of hepatitis C virus NS3 protease Arg155 variants: sensitivity to telaprevir (VX-950) and interferon alpha
    Yi Zhou
    Vertex Pharmaceuticals Inc, Cambridge, Massachusetts 02139, USA
    J Biol Chem 282:22619-28. 2007
    ..Finally, these variant replicons were shown to have reduced replication capacity compared with the wild-type HCV replicon in cells...
  8. pmc NS3 helicase domains involved in infectious intracellular hepatitis C virus particle assembly
    Yinghong Ma
    Center for Hepatitis Research, The University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX 77555 1073, USA
    J Virol 82:7624-39. 2008
    ..These data reveal a previously unsuspected role for the NS3 helicase in early virion morphogenesis and provide a new perspective on HCV assembly...
  9. doi The non-structural 5A protein of hepatitis C virus exhibits genotypic differences in interferon antagonism
    Ya Hui Tsai
    Graduate Institute of Microbiology, National Taiwan University College of Medicine, Taipei 100, Taiwan
    J Hepatol 49:899-907. 2008
    ..In this study, we investigated whether the non-structural 5A protein (NS5A) of HCV genotypes 1 and 2 (1b-NS5A and 2a-NS5A, respectively) exerted differential counteractivities against IFN treatment...
  10. doi Compensatory mutations in NS3 and NS5A proteins enhance the virus production capability of hepatitis C reporter virus
    Qingxia Han
    State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People s Republic of China
    Virus Res 145:63-73. 2009
    ..Further analysis revealed that the M260K and T462I substitutions in NS3 and NS5A, respectively, were the key mutations. These adaptive mutations were also effective in the context of the JFH-1 genome...
  11. pmc NS5A, a nonstructural protein of hepatitis C virus, binds growth factor receptor-bound protein 2 adaptor protein in a Src homology 3 domain/ligand-dependent manner and perturbs mitogenic signaling
    S L Tan
    Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 96:5533-8. 1999
    ..Therefore, NS5A may function to perturb Grb2-mediated signaling pathways by selectively targeting the adaptor. These findings highlight a viral interceptor of cellular signaling with potential implications for HCV pathogenesis...
  12. ncbi T cell dysfunction by hepatitis C virus core protein involves PD-1/PDL-1 signaling
    Zhi Q Yao
    Department of Internal Medicine, James H Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee 37614, USA
    Viral Immunol 20:276-87. 2007
    ..This upregulation of the PD-1 and PDL-1 pathway in humans represents a novel and perhaps common mechanism by which a virus usurps host machinery to facilitate persistence...
  13. pmc Hepatitis C viral NS3-4A protease activity is enhanced by the NS3 helicase
    Rudolf K F Beran
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
    J Biol Chem 283:29929-37. 2008
    ..NS3-4A domain interdependence has important implications for function during the viral lifecycle as well as for the design of inhibitor screens that target the NS3-4A protease...
  14. pmc A conserved proline between domains II and III of hepatitis C virus NS5A influences both RNA replication and virus assembly
    Mair Hughes
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Virol 83:10788-96. 2009
    ..These data point to critical roles for these proline residues at multiple stages in the HCV life cycle; however, they also caution against extrapolation of data from culture-adapted replicons to infectious virus...
  15. pmc Hepatitis C virus core protein induces neuroimmune activation and potentiates Human Immunodeficiency Virus-1 neurotoxicity
    Pornpun Vivithanaporn
    Division of Neurology, University of Alberta, Edmonton, Alberta, Canada
    PLoS ONE 5:e12856. 2010
    ..Herein, we investigate HCV infectivity and effects on neuronal survival and neuroinflammation in conjunction with HIV infection...
  16. pmc Dimerization-driven interaction of hepatitis C virus core protein with NS3 helicase
    G Mousseau
    Department of Infectology, The Scripps Research Institute, Scripps Florida, 130 Scripps Way, 3C1, Jupiter, FL 33458, USA
    J Gen Virol 92:101-11. 2011
    ....
  17. pmc Y-box-binding protein 1 interacts with hepatitis C virus NS3/4A and influences the equilibrium between viral RNA replication and infectious particle production
    Laurent Chatel-Chaix
    Institut de recherche en Immunologie et en Cancérologie, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec H3C 3J7, Canada
    J Virol 85:11022-37. 2011
    ..Our data support that HCV hijacks YB-1-containing ribonucleoparticles and that YB-1-NS3/4A-HCV RNA complexes regulate the equilibrium between HCV RNA replication and viral particle production...
  18. doi Analysis of the PKR-eIF2alpha phosphorylation homology domain (PePHD) of hepatitis C virus genotype 1 in HIV-coinfected patients by ultra-deep pyrosequencing and its relationship to responses to pegylated interferon-ribavirin treatment
    F Bolcic
    Departamento de Microbiologia, Facultad de Medicina UBA, Centro Nacional de Referencia para el SIDA, Paraguay 2155, Piso 11, C1121ABG, Buenos Aires, Argentina
    Arch Virol 157:703-11. 2012
    ..The HCV-E2-PePHD sequence before or during treatment cannot be used to predict reliably the outcome of treatment in patients coinfected with HCV genotype 1 and HIV...
  19. pmc A conserved Gly436-Trp-Leu-Ala-Gly-Leu-Phe-Tyr motif in hepatitis C virus glycoprotein E2 is a determinant of CD81 binding and viral entry
    Heidi E Drummer
    The Macfarlane Burnet Institute for Medical Research and Public Health Ltd, GPO Box 2284, Melbourne, Victoria, Australia 3001
    J Virol 80:7844-53. 2006
    ..These findings indicate that the G436WLAGLFY motif of E2 functions in CD81 binding and in pre- or post-CD81-dependent stages of viral entry...
  20. pmc Mutations in hepatitis C virus E2 located outside the CD81 binding sites lead to escape from broadly neutralizing antibodies but compromise virus infectivity
    Zhen Yong Keck
    Department of Pathology, Stanford University, Stanford, California 94305, USA
    J Virol 83:6149-60. 2009
    ..Mutations that are outside receptor binding sites resulted in structural changes leading to complete escape from domain B neutralizing antibodies, while simultaneously compromising viral fitness by reducing binding to CD81...
  21. ncbi Hepatitis C virus NS5A colocalizes with the core protein on lipid droplets and interacts with apolipoproteins
    Stephanie T Shi
    Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, California 90033, USA
    Virology 292:198-210. 2002
    ....
  22. pmc Hepatitis C virus envelope glycoprotein E2 glycans modulate entry, CD81 binding, and neutralization
    Emilia Falkowska
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Virol 81:8072-9. 2007
    ..Our results show that HCV envelope-associated glycans play a crucial role in masking functionally important regions of E2 and suggest a new strategy for eliciting highly neutralizing antibodies against this virus...
  23. pmc Identification of residues required for RNA replication in domains II and III of the hepatitis C virus NS5A protein
    Timothy L Tellinghuisen
    Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, Box 64, New York, NY 10065, USA
    J Virol 82:1073-83. 2008
    ..These results indicate that the entire domain III region and large portions of domain II of the NS5A protein are not required for the function of NS5A in HCV RNA replication...
  24. pmc Identification of a residue in hepatitis C virus E2 glycoprotein that determines scavenger receptor BI and CD81 receptor dependency and sensitivity to neutralizing antibodies
    Joe Grove
    Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom
    J Virol 82:12020-9. 2008
    ..Our data suggest that a balanced interplay between HCV particles, lipoprotein components, and viral receptors allows the evasion of host immune responses...
  25. pmc Hepatitis C virus NS2 protein contributes to virus particle assembly via opposing epistatic interactions with the E1-E2 glycoprotein and NS3-NS4A enzyme complexes
    Tung Phan
    Section of Microbial Pathogenesis, Yale University School of Medicine, 295 Congress Ave, New Haven, CT 06536, USA
    J Virol 83:8379-95. 2009
    ..These data reveal a complex network of interactions involving NS2 and other viral structural and nonstructural proteins during virus assembly...
  26. pmc Dissociation of a MAVS/IPS-1/VISA/Cardif-IKKepsilon molecular complex from the mitochondrial outer membrane by hepatitis C virus NS3-4A proteolytic cleavage
    Rongtuan Lin
    Lady Davis Institute for Medical Research, McGill University, Montreal H3T 1E2, Quebec, Canada
    J Virol 80:6072-83. 2006
    ..These observations provide an outline of the mechanism by which hepatitis C virus evades the interferon antiviral response...
  27. pmc Proteasomal turnover of hepatitis C virus core protein is regulated by two distinct mechanisms: a ubiquitin-dependent mechanism and a ubiquitin-independent but PA28gamma-dependent mechanism
    Ryosuke Suzuki
    Department of Virology II, National Institute of Infectious Diseases, Tokyo 162 8640, Japan
    J Virol 83:2389-92. 2009
    ..Our results suggest that turnover of this multifunctional viral protein can be tightly controlled via dual ubiquitin-dependent and -independent proteasomal pathways...
  28. doi Cross-talk between programmed death-1 and suppressor of cytokine signaling-1 in inhibition of IL-12 production by monocytes/macrophages in hepatitis C virus infection
    Ying Zhang
    Department of Internal Medicine, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA
    J Immunol 186:3093-103. 2011
    ....
  29. 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
    ....
  30. doi HCV NS3/4A protein activates HIV-1 transcription from its long terminal repeat
    Xiaoyun Wu
    State Key Laboratory of Virology and the Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan 430072, PR China
    Virus Res 135:155-60. 2008
    ..These results have provided insights into the mechanism involved in the co-infection of HCV and HIV...
  31. pmc Genetic analysis of the carboxy-terminal region of the hepatitis C virus core protein
    Martina Kopp
    Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Ave, New York, NY 10065, USA
    J Virol 84:1666-73. 2010
    ..Here, we performed genetic analyses to map the essential determinants of the HCV core C-terminal region, as well as to define the minimal length of the protein that can function for infectious virus production in trans...
  32. doi Hepatitis C virus genotype-3a core protein enhances sterol regulatory element-binding protein-1 activity through the phosphoinositide 3-kinase-Akt-2 pathway
    Candice Jackel-Cram
    Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
    J Gen Virol 91:1388-95. 2010
    ..These results indicate a role for PI3K and Akt-2 in increasing SREBP-1 activity by HCV-3a core protein and provide a mechanism of steatosis caused by HCV...
  33. doi Modulation of interferon signaling by hepatitis C virus non-structural 5A protein: implication of genotypic difference in interferon treatment
    Sang Min Kang
    National Research Laboratory of Hepatitis C Virus, Ilsong Institute of Life Science, Hallym University, Dongan Gu, Anyang, Republic of Korea
    FEBS Lett 584:4069-76. 2010
    ..These data imply that some other host factor may be involved in genotypic differences of IFN antagonism in HCV patients...
  34. doi Association of Vpu with hepatitis C virus NS3/4A stimulates transcription of type 1 human immunodeficiency virus
    Lei Kang
    State Key Laboratory of Virology, College of Life Sciences, and Chinese French Liver Disease Research Institute at Zhongnan Hospital, Wuhan University, Wuhan 430072, China
    Virus Res 163:74-81. 2012
    ..This study enriched our understanding on HIV-1/HCV co-infection and provided new insights in molecular mechanism involved in the co-infection of the two viruses...
  35. ncbi The hepatitis C virus core protein interacts with NS5A and activates its caspase-mediated proteolytic cleavage
    P Y Goh
    Collaborative Anti Viral Research Group, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609
    Virology 290:224-36. 2001
    ..In cells infected by the HCV, core may provide the intrinsic apoptotic signal, which produces truncated forms of NS5A. The biological function of core-NS5A interaction and the downstream effect of NS5A cleavage are discussed...
  36. pmc The hepatitis C virus core protein contains a BH3 domain that regulates apoptosis through specific interaction with human Mcl-1
    Nur Khairiah Mohd-Ismail
    Collaborative Anti Viral Research Group, Institute of Molecular and Cell Biology, Singapore
    J Virol 83:9993-10006. 2009
    ..Taken together, the core protein is a novel BH3-only viral homologue that contributes to the induction of apoptosis during HCV infection...
  37. doi A single point mutation in E2 enhances hepatitis C virus infectivity and alters lipoprotein association of viral particles
    Wanyin Tao
    Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 225 South Chongqing Road, Shanghai, China
    Virology 395:67-76. 2009
    ..Our results provided more insights into understanding the roles of lipoprotein associations in HCV life cycle...
  38. pmc Kinetic analysis of the nucleic acid chaperone activity of the hepatitis C virus core protein
    Kamal Kant Sharma
    Laboratorie de Biophotonique et Pharmacologie, UMR 7213 CNRS, Faculte de Pharmacie, Universite de Strasbourg, 74, route du Rhin, 67401, Illkirch, Cedex, France
    Nucleic Acids Res 38:3632-42. 2010
    ..The three peptides operate similarly, confirming that the core chaperone properties are mostly supported by its basic clusters...
  39. pmc Identification of conserved residues in the E2 envelope glycoprotein of the hepatitis C virus that are critical for CD81 binding
    Ania M Owsianka
    MRC Virology Unit, Institute of Virology, University of Glasgow, UK
    J Virol 80:8695-704. 2006
    ..Specific amino acids conserved across all genotypes that were critical for CD81 binding were W420, Y527, W529, G530, and D535. These data significantly increase our understanding of the CD81 receptor-E2 binding process...
  40. pmc Characterization of determinants important for hepatitis C virus p7 function in morphogenesis by using trans-complementation
    Christiane Brohm
    Department of Molecular Virology, University Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany
    J Virol 83:11682-93. 2009
    ..The experimental system described here should be helpful to investigate further key determinants of p7 that are essential for its structure and function in the absence of secondary effects caused by altered polyprotein processing...
  41. ncbi Structural determinants that target the hepatitis C virus core protein to lipid droplets
    Steeve Boulant
    Medical Research Council Virology Unit, Institute of Virology, Church St, Glasgow G11 5JR, Scotland, United Kingdom
    J Biol Chem 281:22236-47. 2006
    ..They also serve as a unique model for elucidating the specificity of protein-lipid interactions between two membrane-bound organelles...
  42. pmc Expression and characterization of a minimal hepatitis C virus glycoprotein E2 core domain that retains CD81 binding
    Kathleen McCaffrey
    Macfarlane Burnet Institute for Medical Research and Public Health, 85 Commercial Rd, Melbourne, Australia
    J Virol 81:9584-90. 2007
    ..Our data provide insights into the E2 structure by suggesting that the three variable regions reside outside a conserved E2 core...
  43. pmc Identification of new functional regions in hepatitis C virus envelope glycoprotein E2
    Anna Albecka
    Institut Pasteur de Lille, Center for Infection and Immunity of Lille, F 59019 Lille, France
    J Virol 85:1777-92. 2011
    ..In conclusion, our study highlights new functional and structural regions in HCV envelope glycoprotein E2...
  44. ncbi Modulation of hepatitis C virus NS3 protease and helicase activities through the interaction with NS4A
    P Gallinari
    Istituto di Ricerche di Biologia Molecolare P Angeletti, Rome, Italy
    Biochemistry 38:5620-32. 1999
    ..Therefore, NS4A appears to uncouple the ATPase/ssRNA binding and RNA unwinding activities associated with NS3...
  45. ncbi A genomic approach of the hepatitis C virus generates a protein interaction map
    M Flajolet
    INSERM U163, Institut Pasteur, Paris, France
    Gene 242:369-79. 2000
    ..Interacting domains of the viral polyprotein are identified, opening the possibility of developing specific anti-viral agents, based on their ability to modulate these interactions...
  46. pmc Identification of amino acid residues in CD81 critical for interaction with hepatitis C virus envelope glycoprotein E2
    A Higginbottom
    Department of Molecular Biology, University of Sheffield, Sheffield S10 2UH, United Kingdom
    J Virol 74:3642-9. 2000
    ..These observations have implications for the design of soluble high-affinity molecules that could target the CD81-E2 interaction site(s)...
  47. pmc Binding of hepatitis C virus E2 glycoprotein to CD81 does not correlate with species permissiveness to infection
    A Meola
    Istituto di Ricerche di Biologia Molecolare P Angeletti IRBM, Pomezia Roma, Italy
    J Virol 74:5933-8. 2000
    ..These results indicate that the binding of E2 to CD81 is not predictive of an infection-producing interaction between HCV and host cells...
  48. pmc Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR
    Stefan Pohlmann
    Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Virol 77:4070-80. 2003
    ..HCV interactions with DC-SIGN and DC-SIGNR may contribute to the establishment or persistence of infection both by the capture and delivery of virus to the liver and by modulating dendritic cell function...
  49. ncbi Hepatitis C virus glycoprotein E2 contains a membrane-proximal heptad repeat sequence that is essential for E1E2 glycoprotein heterodimerization and viral entry
    Heidi E Drummer
    St Vincent s Institute of Medical Research, 41 Victoria Pde Fitzroy, Victoria Australia 3065
    J Biol Chem 279:30066-72. 2004
    ..Our data indicate that the membraneproximal heptad repeat of E2 is functionally homologous to the stem of flavivirus E glycoproteins. We propose that E2 has mechanistic features in common with class II fusion proteins...
  50. ncbi Molecular determinants of TRIF proteolysis mediated by the hepatitis C virus NS3/4A protease
    Josephine C Ferreon
    Department of Microbiology and Immunology, Center for Hepatitis Research, Institute for Human Infections and Immunity, University of Texas Medical Branch at Galveston, Galveston, Texas 77555 1019, USA
    J Biol Chem 280:20483-92. 2005
    ..Because SH3 binding motifs are also present in NS5A, a viral protein that interacts with NS3, we speculate that the NS3 3(10) helix may be a site of interaction with other viral proteins...
  51. pmc Inhibition of RIG-I-dependent signaling to the interferon pathway during hepatitis C virus expression and restoration of signaling by IKKepsilon
    Adrien Breiman
    Unité Hépacivirus, Institut Pasteur, 75724 Paris Cedex 15, France
    J Virol 79:3969-78. 2005
    ..The partial restoration of the capacity of the host cell to transcribe IFN-beta indicates that IKKepsilon expression is able to bypass the HCV-mediated inhibition and restore the innate antiviral response...
  52. pmc Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase
    Timothy L Tellinghuisen
    Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue Box 64, New York, New York 10021, USA
    Nature 435:374-9. 2005
    ..5-A resolution, which contains a novel fold, a new zinc-coordination motif and a disulphide bond. We use molecular surface analysis to suggest the location of protein-, RNA- and membrane-interaction sites...
  53. ncbi Evidence for the formation of a heptameric ion channel complex by the hepatitis C virus p7 protein in vitro
    Dean Clarke
    Institute of Molecular and Cellular Biology, University of Leeds, Faculty of Biological Sciences, Garstang Building, Leeds, West Yorkshire LS2 9JT, United Kingdom
    J Biol Chem 281:37057-68. 2006
    ..These data validate this system as a means of generating high resolution structural information on the p7 ion channel complex...
  54. ncbi Mutagenesis of a conserved fusion peptide-like motif and membrane-proximal heptad-repeat region of hepatitis C virus glycoprotein E1
    Heidi E Drummer
    Macfarlane Burnet Institute for Medical Research and Public Health Ltd, GPO Box 2284, Melbourne 3001, Australia
    J Gen Virol 88:1144-8. 2007
    ..Our data suggest that E1 is unlikely to function in an analogous manner to other class II fusion glycoproteins...
  55. pmc Spring-loaded mechanism of DNA unwinding by hepatitis C virus NS3 helicase
    Sua Myong
    Physics Department, University of Illinois, 1110 West Green Street, Urbana, IL 61801, USA
    Science 317:513-6. 2007
    ..Such repetitive unwinding behavior over a short stretch of duplex may help to keep secondary structures resolved during viral genome replication...
  56. doi The pre-transmembrane region of the HCV E1 envelope glycoprotein: interaction with model membranes
    Ana J Pérez-Berná
    Instituto de Biologia Molecular y Celular, Edf Torregaitán, Campus de Elche, Universidad Miguel Hernandez, E 03202 Elche Alicante, Spain
    Biochim Biophys Acta 1778:2069-80. 2008
    ..These data support its role in HCV-mediated membrane fusion and suggest that the mechanism of membrane fusion elicited by class I and II fusion proteins might be similar...
  57. ncbi Homotypic interaction and multimerization of hepatitis C virus core protein
    M Matsumoto
    Howard Hughes Medical Institute, University of Southern California School of Medicine, Los Angeles, California, 90033, USA
    Virology 218:43-51. 1996
    ....
  58. pmc Interaction between hepatitis C virus core protein and E1 envelope protein
    S Y Lo
    Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles 90033, USA
    J Virol 70:5177-82. 1996
    ..The implications of these findings on the morphogenesis of the hepatitis C virus virion are discussed...
  59. ncbi Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA
    A A Kolykhalov
    Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110 1093, USA
    Science 277:570-4. 1997
    ..This work defines the structure of a functional HCV genome RNA and proves that HCV alone is sufficient to cause disease...
  60. ncbi Hepatitis C virus core protein interacts with a human DEAD box protein DDX3
    A M Owsianka
    Medical Research Council Virology Unit, Church Street, Glasgow, G11 5JR, United Kingdom
    Virology 257:330-40. 1999
    ..Their role in RNA metabolism or gene expression is unknown. The significance of core-helicase interaction in HCV replication and pathogenesis is discussed...
  61. 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...
  62. ncbi Hepatitis C virus NS5A protein modulates transcription through a novel cellular transcription factor SRCAP
    A K Ghosh
    Department of Pathology, Saint Louis University, St Louis, Missouri 63104, USA
    J Biol Chem 275:7184-8. 2000
    ..Together these results suggest that the interaction of NS5A and SRCAP may be one of the mechanisms by which NS5A exerts its effect on cell growth regulation contributing to hepatitis C virus-mediated pathogenesis...
  63. pmc Subcellular localization and topology of the p7 polypeptide of hepatitis C virus
    Séverine Carrère-Kremer
    CNRS FRE2369, Institut de Biologie de Lille Institut Pasteur de Lille, 59021 Lille Cedex, France
    J Virol 76:3720-30. 2002
    ..Altogether, these data indicate that p7 is a polytopic membrane protein that could have a functional role in several compartments of the secretory pathway...
  64. ncbi Hepatitis C virus NS5A protein binds TBP and p53, inhibiting their DNA binding and p53 interactions with TBP and ERCC3
    Ishtiaq Qadri
    Department of Medicine, Division of Gastroenterology and Hepatology, Hepatobiliary Center, University of Colorado Health Sciences Center, B 145, 4200 E, 9th Avenue, Denver 80262, USA
    Biochim Biophys Acta 1592:193-204. 2002
    ..This could explain one of the possible mechanism(s) by which NS5A is able to exert its effect on cellular gene expression and cell growth regulation...
  65. ncbi Identification and characterization of amphiphysin II as a novel cellular interaction partner of the hepatitis C virus NS5A protein
    Birgit Zech
    Axxima Pharmaceuticals AG, Am Klopferspitz 19, 82152 Martinsried, Germany
    J Gen Virol 84:555-60. 2003
    ....
  66. pmc Protein-protein interactions between hepatitis C virus nonstructural proteins
    Maria Dimitrova
    INSERM UMR_U544, Institut de Virologie, 67000 Strasbourg, France
    J Virol 77:5401-14. 2003
    ..We have been able to demonstrate the existence of a complex network of interactions implicating all six NS proteins. Our observations confirm previously described associations and identify several novel homo- and heterodimerizations...
  67. ncbi The hepatitis C virus NS5A protein binds to members of the Src family of tyrosine kinases and regulates kinase activity
    Andrew Macdonald
    Division of Microbiology, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
    J Gen Virol 85:721-9. 2004
    ..We conclude that the interactions between NS5A and Src-family kinases are physiologically relevant and may play a role in either virus replication or pathogenesis...
  68. ncbi Hepatitis C viral proteins interact with Smad3 and differentially regulate TGF-beta/Smad3-mediated transcriptional activation
    Pei Lin Cheng
    Institute of Biochemistry, National Yang Ming University, Taipei, Taiwan 112, Republic of China
    Oncogene 23:7821-38. 2004
    ..This functional counteraction of TGF-beta responses provides insights into possible mechanisms, whereby the HCV oncogenic proteins antagonize the host defenses during hepatocarcinogenesis...
  69. ncbi The NS5A protein of hepatitis C virus is a zinc metalloprotein
    Timothy L Tellinghuisen
    Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, New York 10021, USA
    J Biol Chem 279:48576-87. 2004
    ..Collectively, these results indicate that NS5A is a zinc metalloprotein and that zinc coordination is likely required for NS5A function in the hepatitis C replicase...
  70. ncbi A hepatitis C virus-encoded, nonstructural protein (NS3) triggers dysfunction and apoptosis in lymphocytes: role of NADPH oxidase-derived oxygen radicals
    Fredrik Thoren
    Department of Clinical Virology, Goteborg University, Guldhedsgatan 10B, S 413 46 Goteborg, Sweden
    J Leukoc Biol 76:1180-6. 2004
    ....
  71. ncbi Further studies on hepatitis C virus NS5A-SH3 domain interactions: identification of residues critical for binding and implications for viral RNA replication and modulation of cell signalling
    Andrew Macdonald
    School of Biochemistry and Microbiology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
    J Gen Virol 86:1035-44. 2005
    ..It is more likely that they play a role in altering the cellular environment to favour viral persistence...
  72. ncbi Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase
    Koichi Watashi
    Laboratory of Human Tumor Viruses, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606 8507, Japan
    Mol Cell 19:111-22. 2005
    ..Thus, CyPB functions as a stimulatory regulator of NS5B in HCV replication machinery. This regulation mechanism for viral replication identifies CyPB as a target for antiviral therapeutic strategies...
  73. ncbi Assembly of functional hepatitis C virus glycoproteins on infectious pseudoparticles occurs intracellularly and requires concomitant incorporation of E1 and E2 glycoproteins
    Virginie Sandrin
    INSERM, U412, Lyon, F 69007, France
    J Gen Virol 86:3189-99. 2005
    ..Altogether, these results confirm that the E1E2 heterodimer constitutes the prebudding form of functional HCV GPs and, more specifically, show that dimerization with E2 is a prerequisite for efficient E1 incorporation onto particles...
  74. ncbi Complex formation between hepatitis C virus NS2 and NS3 proteins
    Kaja Kiiver
    Department of Microbiology and Virology, Institute of Molecular and Cell Biology, Tartu University, Riia Street 23, 51010 Tartu, Estonia
    Virus Res 117:264-72. 2006
    ..This observation suggests the existence of direct interaction between these two proteins that may have importance for the formation of the whole HCV replication complex...
  75. pmc RNA translocation and unwinding mechanism of HCV NS3 helicase and its coordination by ATP
    Sophie Dumont
    Biophysics Graduate Group, University of California, Berkeley, California 94720, USA
    Nature 439:105-8. 2006
    ..The assay developed here should be useful in investigating a broad range of nucleic acid translocation motors...
  76. pmc The alpha isoform of protein kinase CKI is responsible for hepatitis C virus NS5A hyperphosphorylation
    Manuela Quintavalle
    Istituto di Ricerche di Biologia Molecolare P Angeletti, 00040 Pomezia Roma, Italy
    J Virol 80:11305-12. 2006
    ..Finally, we showed that down-regulation of CKI-alpha attenuates HCV RNA replication...
  77. pmc Hepatitis C virus RNA replication is regulated by FKBP8 and Hsp90
    Toru Okamoto
    Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
    EMBO J 25:5015-25. 2006
    ..These results suggest that the complex consisting of NS5A, FKBP8, and Hsp90 plays an important role in HCV RNA replication...
  78. pmc Immunogenic and functional organization of hepatitis C virus (HCV) glycoprotein E2 on infectious HCV virions
    Zhen Yong Keck
    Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA
    J Virol 81:1043-7. 2007
    ..Collectively, these findings support an immunogenic model of HCV E2 having three immunogenic domains with distinct structures and functions and provide added support for the idea that CD81 is required for virus entry...
  79. pmc E6AP ubiquitin ligase mediates ubiquitylation and degradation of hepatitis C virus core protein
    Masayuki Shirakura
    Department of Virology II, National Institute of Infectious Diseases, 1 23 1 Toyama, Shinjuku ku, Tokyo 162 8640, Japan
    J Virol 81:1174-85. 2007
    ..We propose that the E6AP-mediated ubiquitin-proteasome pathway may affect the production of HCV particles through controlling the amounts of viral nucleocapsid protein...
  80. ncbi Up-regulation of fatty acid synthase promoter by hepatitis C virus core protein: genotype-3a core has a stronger effect than genotype-1b core
    Candice Jackel-Cram
    Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
    J Hepatol 46:999-1008. 2007
    ..Hepatitis C virus genotype-3a (HCV-3a) is directly linked to steatosis development. We studied the effects of HCV-3a core protein on the promoter activity of fatty acid synthase (FAS), a major enzyme involved in de novo lipid synthesis...
  81. ncbi The hepatitis C virus NS2/3 protease
    Sarah Welbourn
    McGill Cancer Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    Curr Issues Mol Biol 9:63-9. 2007
    ..However, several recent studies are beginning to clarify possible roles of the cleaved NS2 protein in modulation of host cell gene expression and apoptosis...
  82. pmc Identification of determinants involved in initiation of hepatitis C virus RNA synthesis by using intergenotypic replicase chimeras
    Marco Binder
    University of Heidelberg, Department of Molecular Virology, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany
    J Virol 81:5270-83. 2007
    ....
  83. pmc The neutralizing activity of anti-hepatitis C virus antibodies is modulated by specific glycans on the E2 envelope protein
    François Helle
    Institut de Biologie de Lille UMR8161, CNRS, Université Lille I and II and Institut Pasteur de Lille, Lille, France
    J Virol 81:8101-11. 2007
    ..In conclusion, this work indicates that HCV glycans contribute to the evasion of HCV from the humoral immune response...
  84. 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...
  85. pmc Characterization of fusion determinants points to the involvement of three discrete regions of both E1 and E2 glycoproteins in the membrane fusion process of hepatitis C virus
    Dimitri Lavillette
    Universite de Lyon, IFR 128, F 69007 Lyon, France
    J Virol 81:8752-65. 2007
    ....
  86. pmc A Rab-GAP TBC domain protein binds hepatitis C virus NS5A and mediates viral replication
    Ella H Sklan
    Division of Gastroenterology and Hepatology, Stanford University School of Medicine, CCSR 3115A, 269 Campus Drive, Palo Alto, CA 94305 5187, USA
    J Virol 81:11096-105. 2007
    ..These results suggest that pharmacologic disruption of this NS5A-interacting partner can be contemplated as a potential new antiviral strategy against a pathogen affecting nearly 3% of the world's population...
  87. ncbi The serine protease domain of hepatitis C viral NS3 activates RNA helicase activity by promoting the binding of RNA substrate
    Rudolf K F Beran
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
    J Biol Chem 282:34913-20. 2007
    ....
  88. pmc Specific polymorphisms in hepatitis C virus genotype 3 core protein associated with intracellular lipid accumulation
    Ravi Jhaveri
    Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Infect Dis 197:283-91. 2008
    ..We hypothesize that specific sequence polymorphisms in HCV genotype 3 core protein may be associated with hepatic intracellular lipid accumulation...
  89. doi HCV core protein interacts with Dicer to antagonize RNA silencing
    Weixian Chen
    The Institute for Viral Hepatitis, Key Laboratory of Molecular Biology on Infectious Diseases of the Ministry of Education, Chongqing Medical University, Chongqing, 400016, China
    Virus Res 133:250-8. 2008
    ..This anti-Dicer ability of core protein may contribute to the persistent viral infection and pathogenesis of HCV...
  90. pmc Dissecting the role of putative CD81 binding regions of E2 in mediating HCV entry: putative CD81 binding region 1 is not involved in CD81 binding
    Katharina B Rothwangl
    Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
    Virol J 5:46. 2008
    ..In addition to assaying infectivity, producer cell expression and HCVpp incorporation of HCV E1 and E2 proteins, CD81 binding profiles, and E1E2 association of mutants were examined...
  91. doi Maturation of hepatitis C virus core protein by signal peptide peptidase is required for virus production
    Paul Targett-Adams
    MRC Virology Unit, Institute of Virology, Glasgow G11 5JR, United Kingdom
    J Biol Chem 283:16850-9. 2008
    ..Moreover, they offer compelling evidence for a function for an intramembrane protease to facilitate the association of core with viral genomes, thereby creating putative sites for assembly of nascent virus particles...
  92. pmc A locking mechanism regulates RNA synthesis and host protein interaction by the hepatitis C virus polymerase
    Sreedhar Chinnaswamy
    Department of Biochemistry and Biophysics, Texas A and M University, College Station, TX 77843 2128, USA
    J Biol Chem 283:20535-46. 2008
    ..Different conformations of the HCV RdRp can thus affect RNA synthesis and interaction with cellular proteins...
  93. 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...
  94. pmc Structural determinants for membrane association and dynamic organization of the hepatitis C virus NS3-4A complex
    Volker Brass
    Department of Medicine II, University of Freiburg, D 79106 Freiburg, Germany
    Proc Natl Acad Sci U S A 105:14545-50. 2008
    ..This model has implications for the functional architecture of the HCV replication complex, proteolytic targeting of host factors, and drug design...
  95. pmc Hepatitis C virus NS5B polymerase exhibits distinct nucleotide requirements for initiation and elongation
    Eric Ferrari
    Department of Virology, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    J Biol Chem 283:33893-901. 2008
    ..Thus, distinct nucleotide requirements exist for initiation and elongation steps catalyzed by the HCV NS5B polymerase...
  96. doi Domain 3 of non-structural protein 5A from hepatitis C virus is natively unfolded
    Xavier Hanoulle
    UGSF, UMR CNRS, IFR, Universite des Sciences et Technologies de Lille, Villeneuve d Ascq, France
    Biochem Biophys Res Commun 381:634-8. 2009
    ..This lack of stable folding is thought to be essential for primary interactions of NS5A-D3 domain with other viral or host proteins, which could stabilize some specific conformations conferring new functional features...
  97. pmc Hepatitis C virus NS2 is a protease stimulated by cofactor domains in NS3
    V Schregel
    Institute for Virology and Cell Biology, University of Lubeck, D 23562 Lubeck, Germany
    Proc Natl Acad Sci U S A 106:5342-7. 2009
    ..These findings give new mechanistic insights into function and regulation of the NS2 protease and have important implications for the development of anti-HCV therapeutics...
  98. pmc Determinants of hepatitis C virus p7 ion channel function and drug sensitivity identified in vitro
    Corine StGelais
    Institute of Molecular and Cellular Biology, Astbury Centre for Structural Molecular Biology, Leeds, West Yorkshire, United Kingdom
    J Virol 83:7970-81. 2009
    ..Mutations predicted to play a structural role affect both channel function and oligomerization kinetics. Lastly, we identify a region at the p7 carboxy terminus which may act as a specific sensitivity determinant for the drug amantadine...
  99. pmc An amphipathic alpha-helix at the C terminus of hepatitis C virus nonstructural protein 4B mediates membrane association
    Jérôme Gouttenoire
    Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, BU44 07 2421, Rue du Bugnon 44, CH 1011 Lausanne, Switzerland
    J Virol 83:11378-84. 2009
    ..Here, we describe an amphipathic alpha-helix at the C terminus of NS4B (amino acid residues 229 to 253) that mediates membrane association and is involved in the formation of a functional HCV replication complex...
  100. pmc Mutagenesis of the fusion peptide-like domain of hepatitis C virus E1 glycoprotein: involvement in cell fusion and virus entry
    Hsiao Fen Li
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
    J Biomed Sci 16:89. 2009
    ..Envelope (E) glycoprotein E2 of the hepatitis C virus (HCV) mediates binding of the virus to target cell receptors. Nevertheless, the precise role of E1 in viral entry remains elusive...
  101. pmc Requirement of cellular DDX3 for hepatitis C virus replication is unrelated to its interaction with the viral core protein
    Allan G N Angus
    MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK
    J Gen Virol 91:122-32. 2010
    ..Thus, our study shows for the first time that the requirement of DDX3 for HCV replication is unrelated to its interaction with the viral core protein...

Research Grants5

  1. Defining NS4B Function in Hepatitis C Virus Replication
    Keril J Blight; Fiscal Year: 2010
    ..abstract_text> ..
  2. Replication Elements in the 5' End of the HCV Genome
    Minkyung Yi; Fiscal Year: 2004
    ..abstract_text> ..
  3. Functions of NS3 in HCV RNA Replication
    Minkyung Yi; Fiscal Year: 2006
    ..abstract_text> ..
  4. Enzymatic Differences Among Hepatitis C Virus Genotypes
    David Frick; Fiscal Year: 2007
    ..abstract_text> ..
  5. 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]..