HCVgp1

Summary

Gene Symbol: HCVgp1
Description: polyprotein
Species: Hepatitis C virus genotype 1
Products:     HCVgp1

Top Publications

  1. Ma Y, Anantpadma M, Timpe J, Shanmugam S, Singh S, Lemon S, et al. Hepatitis C virus NS2 protein serves as a scaffold for virus assembly by interacting with both structural and nonstructural proteins. J Virol. 2011;85:86-97 pubmed publisher
    ..p7 may play an accessory role by regulating NS2 membrane topology, which is important for NS2-mediated protein interactions and therefore NS2 function. ..
  2. Keck Z, Xia J, Cai Z, Li T, Owsianka A, Patel A, et al. Immunogenic and functional organization of hepatitis C virus (HCV) glycoprotein E2 on infectious HCV virions. J Virol. 2007;81:1043-7 pubmed
    ..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. ..
  3. Murray C, Jones C, Tassello J, Rice C. Alanine scanning of the hepatitis C virus core protein reveals numerous residues essential for production of infectious virus. J Virol. 2007;81:10220-31 pubmed
  4. Jirasko V, Montserret R, Lee J, Gouttenoire J, Moradpour D, Penin F, et al. Structural and functional studies of nonstructural protein 2 of the hepatitis C virus reveal its key role as organizer of virion assembly. PLoS Pathog. 2010;6:e1001233 pubmed publisher
    ..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. ..
  5. Beran R, Pyle A. Hepatitis C viral NS3-4A protease activity is enhanced by the NS3 helicase. J Biol Chem. 2008;283:29929-37 pubmed publisher
    ..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. ..
  6. Milward A, Mankouri J, Harris M. Hepatitis C virus NS5A protein interacts with beta-catenin and stimulates its transcriptional activity in a phosphoinositide-3 kinase-dependent fashion. J Gen Virol. 2010;91:373-81 pubmed publisher
    ..This may contribute to the association between chronic HCV infection and the development of HCC. ..
  7. Han Q, Xu C, Wu C, Zhu W, Yang R, Chen X. Compensatory mutations in NS3 and NS5A proteins enhance the virus production capability of hepatitis C reporter virus. Virus Res. 2009;145:63-73 pubmed publisher
    ..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. ..
  8. Brohm C, Steinmann E, Friesland M, Lorenz I, Patel A, Penin F, et al. Characterization of determinants important for hepatitis C virus p7 function in morphogenesis by using trans-complementation. J Virol. 2009;83:11682-93 pubmed publisher
    ..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. ..
  9. Binder M, Quinkert D, Bochkarova O, Klein R, Kezmic N, Bartenschlager R, et al. Identification of determinants involved in initiation of hepatitis C virus RNA synthesis by using intergenotypic replicase chimeras. J Virol. 2007;81:5270-83 pubmed
  10. Tellinghuisen T, Foss K, Treadaway J, Rice C. Identification of residues required for RNA replication in domains II and III of the hepatitis C virus NS5A protein. J Virol. 2008;82:1073-83 pubmed
    ..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. ..

Detail Information

Publications82

  1. Ma Y, Anantpadma M, Timpe J, Shanmugam S, Singh S, Lemon S, et al. Hepatitis C virus NS2 protein serves as a scaffold for virus assembly by interacting with both structural and nonstructural proteins. J Virol. 2011;85:86-97 pubmed publisher
    ..p7 may play an accessory role by regulating NS2 membrane topology, which is important for NS2-mediated protein interactions and therefore NS2 function. ..
  2. Keck Z, Xia J, Cai Z, Li T, Owsianka A, Patel A, et al. Immunogenic and functional organization of hepatitis C virus (HCV) glycoprotein E2 on infectious HCV virions. J Virol. 2007;81:1043-7 pubmed
    ..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. ..
  3. Murray C, Jones C, Tassello J, Rice C. Alanine scanning of the hepatitis C virus core protein reveals numerous residues essential for production of infectious virus. J Virol. 2007;81:10220-31 pubmed
  4. Jirasko V, Montserret R, Lee J, Gouttenoire J, Moradpour D, Penin F, et al. Structural and functional studies of nonstructural protein 2 of the hepatitis C virus reveal its key role as organizer of virion assembly. PLoS Pathog. 2010;6:e1001233 pubmed publisher
    ..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. ..
  5. Beran R, Pyle A. Hepatitis C viral NS3-4A protease activity is enhanced by the NS3 helicase. J Biol Chem. 2008;283:29929-37 pubmed publisher
    ..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. ..
  6. Milward A, Mankouri J, Harris M. Hepatitis C virus NS5A protein interacts with beta-catenin and stimulates its transcriptional activity in a phosphoinositide-3 kinase-dependent fashion. J Gen Virol. 2010;91:373-81 pubmed publisher
    ..This may contribute to the association between chronic HCV infection and the development of HCC. ..
  7. Han Q, Xu C, Wu C, Zhu W, Yang R, Chen X. Compensatory mutations in NS3 and NS5A proteins enhance the virus production capability of hepatitis C reporter virus. Virus Res. 2009;145:63-73 pubmed publisher
    ..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. ..
  8. Brohm C, Steinmann E, Friesland M, Lorenz I, Patel A, Penin F, et al. Characterization of determinants important for hepatitis C virus p7 function in morphogenesis by using trans-complementation. J Virol. 2009;83:11682-93 pubmed publisher
    ..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. ..
  9. Binder M, Quinkert D, Bochkarova O, Klein R, Kezmic N, Bartenschlager R, et al. Identification of determinants involved in initiation of hepatitis C virus RNA synthesis by using intergenotypic replicase chimeras. J Virol. 2007;81:5270-83 pubmed
  10. Tellinghuisen T, Foss K, Treadaway J, Rice C. Identification of residues required for RNA replication in domains II and III of the hepatitis C virus NS5A protein. J Virol. 2008;82:1073-83 pubmed
    ..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. ..
  11. Olenina L, Kuzmina T, Sobolev B, Kuraeva T, Kolesanova E, Archakov A. Identification of glycosaminoglycan-binding sites within hepatitis C virus envelope glycoprotein E2*. J Viral Hepat. 2005;12:584-93 pubmed
    ..Our data supported the specific association between HCV envelope protein E2 and cell surface glycosaminoglycans. We hypothesize that identified regions from E2 can contribute to HCV binding to cell surface glycosaminoglycans. ..
  12. Phan T, Kohlway A, Dimberu P, Pyle A, Lindenbach B. The acidic domain of hepatitis C virus NS4A contributes to RNA replication and virus particle assembly. J Virol. 2011;85:1193-204 pubmed publisher
    ..Taken together, our data reveal interactions between NS4A and NS4B that control genome replication and between NS3 and NS4A that control virus assembly. ..
  13. Yi M, Ma Y, Yates J, Lemon S. Trans-complementation of an NS2 defect in a late step in hepatitis C virus (HCV) particle assembly and maturation. PLoS Pathog. 2009;5:e1000403 pubmed publisher
    ..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. ..
  14. Helle F, Vieyres G, Elkrief L, Popescu C, Wychowski C, Descamps V, et al. Role of N-linked glycans in the functions of hepatitis C virus envelope proteins incorporated into infectious virions. J Virol. 2010;84:11905-15 pubmed publisher
    ..Furthermore, these carbohydrates form a "glycan shield" at the surface of the virion, which contributes to the evasion of HCV from the humoral immune response. ..
  15. Okamoto T, Nishimura Y, Ichimura T, Suzuki K, Miyamura T, Suzuki T, et al. Hepatitis C virus RNA replication is regulated by FKBP8 and Hsp90. EMBO J. 2006;25:5015-25 pubmed
    ..These results suggest that the complex consisting of NS5A, FKBP8, and Hsp90 plays an important role in HCV RNA replication. ..
  16. Lavillette D, Pécheur E, Donot P, Fresquet J, Molle J, Corbau R, et al. 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. J Virol. 2007;81:8752-65 pubmed
  17. Clarke D, Griffin S, Beales L, Gelais C, Burgess S, Harris M, et al. Evidence for the formation of a heptameric ion channel complex by the hepatitis C virus p7 protein in vitro. J Biol Chem. 2006;281:37057-68 pubmed
    ..These data validate this system as a means of generating high resolution structural information on the p7 ion channel complex. ..
  18. Ariumi Y, Kuroki M, Maki M, Ikeda M, Dansako H, Wakita T, et al. The ESCRT system is required for hepatitis C virus production. PLoS ONE. 2011;6:e14517 pubmed publisher
    ..These results suggest that the ESCRT system is required for infectious HCV production. ..
  19. Horner S, Park H, Gale M. Control of innate immune signaling and membrane targeting by the Hepatitis C virus NS3/4A protease are governed by the NS3 helix ?0. J Virol. 2012;86:3112-20 pubmed publisher
    ..Therefore, the hydrophobic amphipathic helix ?(0) of NS3 is required for NS3/4A control of RIG-I signaling and HCV replication by directing the membrane targeting of both viral and cellular substrates. ..
  20. Keck Z, Li S, Xia J, von Hahn T, Balfe P, McKeating J, et al. Mutations in hepatitis C virus E2 located outside the CD81 binding sites lead to escape from broadly neutralizing antibodies but compromise virus infectivity. J Virol. 2009;83:6149-60 pubmed publisher
    ..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. Eyre N, Fiches G, Aloia A, Helbig K, McCartney E, McErlean C, et al. Dynamic imaging of the hepatitis C virus NS5A protein during a productive infection. J Virol. 2014;88:3636-52 pubmed publisher
    ..These studies reveal new details as to the traffic, composition and biogenesis of NS5A foci and the nature of their association with putative sites of virus assembly. ..
  22. Choi S, Hwang S. Modulation of the transforming growth factor-beta signal transduction pathway by hepatitis C virus nonstructural 5A protein. J Biol Chem. 2006;281:7468-78 pubmed
    ..These results indicate that HCV NS5A modulates TGF-beta signaling through interaction with TbetaR-I and that NS5A may be an important risk factor in HCV-associated liver pathogenesis. ..
  23. Tsai Y, Kuang W, Lu T, Kao J, Lai M, Liu C, et al. The non-structural 5A protein of hepatitis C virus exhibits genotypic differences in interferon antagonism. J Hepatol. 2008;49:899-907 pubmed publisher
    ..The V3 and the C-terminus regions are responsible for the differential anti-IFN effects. This phenomenon may partly explain the genotype-linked differences in the response of HCV to IFN treatment. ..
  24. Pérez Berná A, Veiga A, Castanho M, Villalain J. Hepatitis C virus core protein binding to lipid membranes: the role of domains 1 and 2. J Viral Hepat. 2008;15:346-56 pubmed publisher
    ..Furthermore, these membranotropic regions could be envisaged as new possible targets, as inhibition of its interaction with the membrane could potentially lead to new vaccine strategies...
  25. Zhou Y, Müh U, Hanzelka B, Bartels D, Wei Y, Rao B, et al. Phenotypic and structural analyses of hepatitis C virus NS3 protease Arg155 variants: sensitivity to telaprevir (VX-950) and interferon alpha. J Biol Chem. 2007;282:22619-28 pubmed
    ..Finally, these variant replicons were shown to have reduced replication capacity compared with the wild-type HCV replicon in cells. ..
  26. Cook G, Opella S. Secondary structure, dynamics, and architecture of the p7 membrane protein from hepatitis C virus by NMR spectroscopy. Biochim Biophys Acta. 2011;1808:1448-53 pubmed publisher
    ..A solid-state NMR two-dimensional separated local field spectrum of p7 aligned in phospholipid bilayers provided the tilt angles of two of these segments. A preliminary structural model of p7 derived from these NMR data is presented...
  27. Suzuki R, Moriishi K, Fukuda K, Shirakura M, Ishii K, Shoji I, et al. 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. J Virol. 2009;83:2389-92 pubmed publisher
    ..Our results suggest that turnover of this multifunctional viral protein can be tightly controlled via dual ubiquitin-dependent and -independent proteasomal pathways. ..
  28. Khan A, Whidby J, Miller M, Scarborough H, Zatorski A, Cygan A, et al. Structure of the core ectodomain of the hepatitis C virus envelope glycoprotein 2. Nature. 2014;509:381-4 pubmed publisher
    ..Thus, the IgG-like fold is the only feature that E2 shares with class II membrane fusion proteins. These results provide unprecedented insights into HCV entry and will assist in developing an HCV vaccine and new inhibitors. ..
  29. Rothwangl K, Manicassamy B, Uprichard S, Rong L. 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. Virol J. 2008;5:46 pubmed publisher
    ..This region is highly conserved across genotypes, underlining its importance in mediating viral entry. ..
  30. Boulant S, Montserret R, Hope R, Ratinier M, Targett Adams P, Lavergne J, et al. Structural determinants that target the hepatitis C virus core protein to lipid droplets. J Biol Chem. 2006;281:22236-47 pubmed
    ..They also serve as a unique model for elucidating the specificity of protein-lipid interactions between two membrane-bound organelles. ..
  31. Kang S, Won S, Lee G, Lim Y, Hwang S. Modulation of interferon signaling by hepatitis C virus non-structural 5A protein: implication of genotypic difference in interferon treatment. FEBS Lett. 2010;584:4069-76 pubmed publisher
    ..These data imply that some other host factor may be involved in genotypic differences of IFN antagonism in HCV patients. ..
  32. Gouttenoire J, Montserret R, Kennel A, Penin F, Moradpour D. An amphipathic alpha-helix at the C terminus of hepatitis C virus nonstructural protein 4B mediates membrane association. J Virol. 2009;83:11378-84 pubmed publisher
    ..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. ..
  33. Hughes M, Gretton S, Shelton H, Brown D, McCormick C, Angus A, et al. A conserved proline between domains II and III of hepatitis C virus NS5A influences both RNA replication and virus assembly. J Virol. 2009;83:10788-96 pubmed publisher
    ..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. ..
  34. Ferrari E, He Z, Palermo R, Huang H. Hepatitis C virus NS5B polymerase exhibits distinct nucleotide requirements for initiation and elongation. J Biol Chem. 2008;283:33893-901 pubmed publisher
    ..Thus, distinct nucleotide requirements exist for initiation and elongation steps catalyzed by the HCV NS5B polymerase. ..
  35. Blight K. Charged residues in hepatitis C virus NS4B are critical for multiple NS4B functions in RNA replication. J Virol. 2011;85:8158-71 pubmed publisher
    ..Taken together, these findings highlight the importance of charged residues for multiple NS4B functions in HCV RNA replication, including the formation of a functional replication complex. ..
  36. Ross Thriepland D, Amako Y, Harris M. The C terminus of NS5A domain II is a key determinant of hepatitis C virus genome replication, but is not required for virion assembly and release. J Gen Virol. 2013;94:1009-18 pubmed publisher
    ..Comparison of our data with a previously published analysis of the same region in genotype 1b revealed some important differences between the two genotypes of HCV...
  37. Hanoulle X, Verdegem D, Badillo A, Wieruszeski J, Penin F, Lippens G. Domain 3 of non-structural protein 5A from hepatitis C virus is natively unfolded. Biochem Biophys Res Commun. 2009;381:634-8 pubmed publisher
    ..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. ..
  38. Jackel Cram C, Babiuk L, Liu Q. Up-regulation of fatty acid synthase promoter by hepatitis C virus core protein: genotype-3a core has a stronger effect than genotype-1b core. J Hepatol. 2007;46:999-1008 pubmed
    ..The stronger effect of HCV-3a core protein on FAS activation in comparison to HCV-1b core could contribute to the higher prevalence and severity of steatosis in HCV-3a infections. ..
  39. Albecka A, Montserret R, Krey T, Tarr A, Diesis E, Ball J, et al. Identification of new functional regions in hepatitis C virus envelope glycoprotein E2. J Virol. 2011;85:1777-92 pubmed publisher
    ..In conclusion, our study highlights new functional and structural regions in HCV envelope glycoprotein E2. ..
  40. Grove J, Nielsen S, Zhong J, Bassendine M, Drummer H, Balfe P, et al. Identification of a residue in hepatitis C virus E2 glycoprotein that determines scavenger receptor BI and CD81 receptor dependency and sensitivity to neutralizing antibodies. J Virol. 2008;82:12020-9 pubmed publisher
    ..Our data suggest that a balanced interplay between HCV particles, lipoprotein components, and viral receptors allows the evasion of host immune responses. ..
  41. Li H, Huang C, Ai L, Chuang C, Chen S. Mutagenesis of the fusion peptide-like domain of hepatitis C virus E1 glycoprotein: involvement in cell fusion and virus entry. J Biomed Sci. 2009;16:89 pubmed publisher
    ..Our results indicate that specific residues, but not the structure, of this fusion peptide-like domain are required for mediating cell fusion and viral entry. ..
  42. Berger K, Kelly S, Jordan T, Tartell M, Randall G. Hepatitis C virus stimulates the phosphatidylinositol 4-kinase III alpha-dependent phosphatidylinositol 4-phosphate production that is essential for its replication. J Virol. 2011;85:8870-83 pubmed publisher
    ..5 cells and from dually transfected 293T cells. In sum, these results suggest that HCV NS5A modulation of PI4KA-dependent PI4P production influences replication complex formation. ..
  43. Angus A, Dalrymple D, Boulant S, McGivern D, Clayton R, Scott M, et al. Requirement of cellular DDX3 for hepatitis C virus replication is unrelated to its interaction with the viral core protein. J Gen Virol. 2010;91:122-32 pubmed publisher
    ..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. ..
  44. Ross Thriepland D, Harris M. Insights into the complexity and functionality of hepatitis C virus NS5A phosphorylation. J Virol. 2014;88:1421-32 pubmed publisher
    ..We propose that this regulation could drive a conformational switch between the dimeric structures of NS5A and could also explain the different functions of the protein in the virus life cycle. ..
  45. Krey T, D Alayer J, Kikuti C, Saulnier A, Damier Piolle L, Petitpas I, et al. The disulfide bonds in glycoprotein E2 of hepatitis C virus reveal the tertiary organization of the molecule. PLoS Pathog. 2010;6:e1000762 pubmed publisher
  46. Ai L, Lee Y, Chen S. Characterization of hepatitis C virus core protein multimerization and membrane envelopment: revelation of a cascade of core-membrane interactions. J Virol. 2009;83:9923-39 pubmed publisher
    ..The results provide mechanistic insights into the sequential and coordinated processes during the association of the HCV core protein with membranes in the early phase of virus maturation and morphogenesis. ..
  47. Pérez Berná A, Bernabeu A, Moreno M, Guillen J, Villalain J. The pre-transmembrane region of the HCV E1 envelope glycoprotein: interaction with model membranes. Biochim Biophys Acta. 2008;1778:2069-80 pubmed publisher
    ..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. ..
  48. Ding S, Kohlway A, Pyle A. Unmasking the active helicase conformation of nonstructural protein 3 from hepatitis C virus. J Virol. 2011;85:4343-53 pubmed publisher
    ..Our findings indicate that an open, extended conformation of NS3 is required for helicase activity and represents the biologically relevant conformation of the protein during viral replication. ..
  49. Sharma K, Didier P, Darlix J, de Rocquigny H, Bensikaddour H, Lavergne J, et al. Kinetic analysis of the nucleic acid chaperone activity of the hepatitis C virus core protein. Nucleic Acids Res. 2010;38:3632-42 pubmed publisher
    ..The three peptides operate similarly, confirming that the core chaperone properties are mostly supported by its basic clusters. ..
  50. Russell R, Kawaguchi K, Meunier J, Takikawa S, Faulk K, Bukh J, et al. Mutational analysis of the hepatitis C virus E1 glycoprotein in retroviral pseudoparticles and cell-culture-derived H77/JFH1 chimeric infectious virus particles. J Viral Hepat. 2009;16:621-32 pubmed publisher
    ..This comprehensive mutational analysis of the putative HCV fusion peptide provides insight into the role of E1 in its interaction with E2 and in HCV entry. ..
  51. Harris C, Herker E, Farese R, Ott M. Hepatitis C virus core protein decreases lipid droplet turnover: a mechanism for core-induced steatosis. J Biol Chem. 2011;286:42615-25 pubmed publisher
    ..Our results support a bipartite model in which core first requires DGAT1 to gain access to LDs, and then LD-localized core interferes with triglyceride turnover, thus stabilizing lipid droplets and leading to steatosis. ..
  52. Welbourn S, Pause A. The hepatitis C virus NS2/3 protease. Curr Issues Mol Biol. 2007;9:63-9 pubmed
    ..However, several recent studies are beginning to clarify possible roles of the cleaved NS2 protein in modulation of host cell gene expression and apoptosis. ..
  53. Backes P, Quinkert D, Reiss S, Binder M, Zayas M, Rescher U, et al. Role of annexin A2 in the production of infectious hepatitis C virus particles. J Virol. 2010;84:5775-89 pubmed publisher
    ..These data identify ANXA2 as a novel host factor contributing, with NS5A, to the formation of infectious HCV particles. ..
  54. Rajagopal V, Gurjar M, Levin M, Patel S. The protease domain increases the translocation stepping efficiency of the hepatitis C virus NS3-4A helicase. J Biol Chem. 2010;285:17821-32 pubmed publisher
    ..These effects of the protease domain on the helicase can be explained by an improved allosteric cross-talk between the ATP- and nucleic acid-binding sites achieved by the overall stabilization of the helicase domain structure. ..
  55. Foster T, Belyaeva T, Stonehouse N, Pearson A, Harris M. All three domains of the hepatitis C virus nonstructural NS5A protein contribute to RNA binding. J Virol. 2010;84:9267-77 pubmed publisher
    ..The preference of NS5A, in contrast to NS5B, for the polypyrimidine tract highlights an aspect of 3' UTR RNA recognition by NS5A which may play a role in the control or enhancement of HCV genome replication. ..
  56. Nevo Yassaf I, Yaffe Y, Asher M, Ravid O, Eizenberg S, Henis Y, et al. Role for TBC1D20 and Rab1 in hepatitis C virus replication via interaction with lipid droplet-bound nonstructural protein 5A. J Virol. 2012;86:6491-502 pubmed publisher
    ..Our results demonstrate the significance of the localization of NS5A to LDs and support a model whereby its interaction with TBC1D20 and Rab1 affects lipid droplet metabolism to promote the viral life cycle. ..
  57. Tao W, Xu C, Ding Q, Li R, Xiang Y, Chung J, et al. A single point mutation in E2 enhances hepatitis C virus infectivity and alters lipoprotein association of viral particles. Virology. 2009;395:67-76 pubmed publisher
    ..Our results provided more insights into understanding the roles of lipoprotein associations in HCV life cycle. ..
  58. Kiiver K, Merits A, Ustav M, Zusinaite E. Complex formation between hepatitis C virus NS2 and NS3 proteins. Virus Res. 2006;117:264-72 pubmed
    ..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. ..
  59. Jhaveri R, McHutchison J, Patel K, Qiang G, Diehl A. Specific polymorphisms in hepatitis C virus genotype 3 core protein associated with intracellular lipid accumulation. J Infect Dis. 2008;197:283-91 pubmed publisher
    ..03). We have identified polymorphisms in HCV core protein genotype 3 that produce increased intracellular lipid levels and thus may play a significant role in lipid metabolism or trafficking, contributing to steatosis. ..
  60. Schregel V, Jacobi S, Penin F, Tautz N. Hepatitis C virus NS2 is a protease stimulated by cofactor domains in NS3. Proc Natl Acad Sci U S A. 2009;106:5342-7 pubmed publisher
    ..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. ..
  61. Dhillon S, Witteveldt J, Gatherer D, Owsianka A, Zeisel M, Zahid M, et al. Mutations within a conserved region of the hepatitis C virus E2 glycoprotein that influence virus-receptor interactions and sensitivity to neutralizing antibodies. J Virol. 2010;84:5494-507 pubmed publisher
    ..The properties of all of these viruses in terms of receptor reactivity and neutralization by human antibodies were similar to JFH1(N415D), highlighting the importance of the E2 412-423 region in virus entry. ..
  62. Su W, Chao T, Huang Y, Weng S, Jeng K, Lai M. Rab5 and class III phosphoinositide 3-kinase Vps34 are involved in hepatitis C virus NS4B-induced autophagy. J Virol. 2011;85:10561-71 pubmed publisher
    ..Taken together, these results not only reveal a novel role of NS4B in autophagy but also offer a clue to the mechanism of HCV-induced autophagy. ..
  63. Mousseau G, Kota S, Takahashi V, Frick D, Strosberg A. Dimerization-driven interaction of hepatitis C virus core protein with NS3 helicase. J Gen Virol. 2011;92:101-11 pubmed publisher
  64. Chen W, Zhang Z, Chen J, Zhang J, Zhang J, Wu Y, et al. HCV core protein interacts with Dicer to antagonize RNA silencing. Virus Res. 2008;133:250-8 pubmed publisher
    ..This anti-Dicer ability of core protein may contribute to the persistent viral infection and pathogenesis of HCV. ..
  65. Thompson A, Zou A, Yan J, Duggal R, Hao W, Molina D, et al. Biochemical characterization of recombinant hepatitis C virus nonstructural protein 4B: evidence for ATP/GTP hydrolysis and adenylate kinase activity. Biochemistry. 2009;48:906-16 pubmed publisher
    ..Mutation of amino acids in the Walker A and B motifs of NS4B resulted in decreased affinity for both GTPgammaS and ATPgammaS as well as decreased ATP hydrolysis and AK activity. ..
  66. Kong L, Giang E, Nieusma T, Kadam R, Cogburn K, Hua Y, et al. Hepatitis C virus E2 envelope glycoprotein core structure. Science. 2013;342:1090-4 pubmed publisher
    ..The x-ray and electron microscopy E2 structures differ markedly from predictions of an extended, three-domain, class II fusion protein fold and therefore provide valuable information for HCV drug and vaccine design. ..
  67. Targett Adams P, Hope G, Boulant S, McLauchlan J. Maturation of hepatitis C virus core protein by signal peptide peptidase is required for virus production. J Biol Chem. 2008;283:16850-9 pubmed publisher
    ..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. ..
  68. Sandrin V, Boulanger P, Penin F, Granier C, Cosset F, Bartosch B. Assembly of functional hepatitis C virus glycoproteins on infectious pseudoparticles occurs intracellularly and requires concomitant incorporation of E1 and E2 glycoproteins. J Gen Virol. 2005;86:3189-99 pubmed
    ..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. ..
  69. Georgopoulou U, Tsitoura P, Kalamvoki M, Mavromara P. The protein phosphatase 2A represents a novel cellular target for hepatitis C virus NS5A protein. Biochimie. 2006;88:651-62 pubmed
    ..We propose that HCV NS5A represents a viral PP2A regulatory protein. This is a novel function for the NS5A protein which may have a key role in the ability of the virus to deregulate cell growth and survival. ..
  70. Owsianka A, Timms J, Tarr A, Brown R, Hickling T, Szwejk A, et al. Identification of conserved residues in the E2 envelope glycoprotein of the hepatitis C virus that are critical for CD81 binding. J Virol. 2006;80:8695-704 pubmed
    ..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. ..
  71. Stapleford K, Lindenbach B. Hepatitis C virus NS2 coordinates virus particle assembly through physical interactions with the E1-E2 glycoprotein and NS3-NS4A enzyme complexes. J Virol. 2011;85:1706-17 pubmed publisher
    ..These studies demonstrate that NS2 plays a central organizing role in HCV particle assembly by bringing together viral structural and nonstructural proteins. ..
  72. Falkowska E, Kajumo F, Garcia E, Reinus J, Dragic T. Hepatitis C virus envelope glycoprotein E2 glycans modulate entry, CD81 binding, and neutralization. J Virol. 2007;81:8072-9 pubmed
    ..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. ..
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    ..These data reveal a previously unsuspected role for the NS3 helicase in early virion morphogenesis and provide a new perspective on HCV assembly. ..
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    ..These results provide the first atomic resolution structure of an essential membrane-associated determinant of HCV NS4B. ..
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    ..Finally, we showed that down-regulation of CKI-alpha attenuates HCV RNA replication. ..
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    ..Our data suggest that E1 is unlikely to function in an analogous manner to other class II fusion glycoproteins. ..
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    ..These data reveal a complex network of interactions involving NS2 and other viral structural and nonstructural proteins during virus assembly. ..
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    ..We propose that the E6AP-mediated ubiquitin-proteasome pathway may affect the production of HCV particles through controlling the amounts of viral nucleocapsid protein. ..
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    ..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. ..