Hepatitis C virus genotype 1

Summary

Alias: Hepatitis C virus type 1, Hepatitis C virus 1, hepatitis C virus 1 HCV 1

Top Publications

  1. Ferreon J, Ferreon A, Li K, Lemon S. Molecular determinants of TRIF proteolysis mediated by the hepatitis C virus NS3/4A protease. J Biol Chem. 2005;280:20483-92 pubmed
    ..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. ..
  2. Goh P, Tan Y, Lim S, Lim S, Tan Y, Hong W. The hepatitis C virus core protein interacts with NS5A and activates its caspase-mediated proteolytic cleavage. Virology. 2001;290:224-36 pubmed
    ..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. ..
  3. Breiman A, Grandvaux N, Lin R, Ottone C, Akira S, Yoneyama M, et al. Inhibition of RIG-I-dependent signaling to the interferon pathway during hepatitis C virus expression and restoration of signaling by IKKepsilon. J Virol. 2005;79:3969-78 pubmed
    ..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. ..
  4. Cheng P, Chang M, Chao C, Lee Y. Hepatitis C viral proteins interact with Smad3 and differentially regulate TGF-beta/Smad3-mediated transcriptional activation. Oncogene. 2004;23:7821-38 pubmed
    ..This functional counteraction of TGF-beta responses provides insights into possible mechanisms, whereby the HCV oncogenic proteins antagonize the host defenses during hepatocarcinogenesis. ..
  5. 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. ..
  6. 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. ..
  7. 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. ..
  8. 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. ..
  9. 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. ..

More Information

Publications128 found, 100 shown here

  1. 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. ..
  2. 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. ..
  3. Yamasaki L, Arcuri H, Jardim A, Bittar C, de Carvalho Mello I, Rahal P. New insights regarding HCV-NS5A structure/function and indication of genotypic differences. Virol J. 2012;9:14 pubmed publisher
    ..Therefore, it emphasizes the importance of using bioinformatics tools in viral studies. Data acquired herein will aid in clarifying the structure/function of this protein and in the development of antiviral agents. ..
  4. Fan Z, Yang Q, Twu J, Sherker A. Specific in vitro association between the hepatitis C viral genome and core protein. J Med Virol. 1999;59:131-4 pubmed
    ..This interaction may be important for the specific encapsidation of the viral genome during HCV replication. ..
  5. 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. ..
  6. 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. ..
  7. 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. ..
  8. 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. ..
  9. Shi S, Polyak S, Tu H, Taylor D, Gretch D, Lai M. Hepatitis C virus NS5A colocalizes with the core protein on lipid droplets and interacts with apolipoproteins. Virology. 2002;292:198-210 pubmed
  10. 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. ..
  11. 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. ..
  12. Wolf M, Dimitrova M, Baumert T, Schuster C. The major form of hepatitis C virus alternate reading frame protein is suppressed by core protein expression. Nucleic Acids Res. 2008;36:3054-64 pubmed publisher
    ..These findings define key mechanisms regulating ARFP expression and set the stage for further studies addressing the function of ARFP within the viral life cycle. ..
  13. Tan S, Nakao H, He Y, Vijaysri S, Neddermann P, Jacobs B, et al. 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. Proc Natl Acad Sci U S A. 1999;96:5533-8 pubmed
    ..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. ..
  14. 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
  15. Zech B, Kurtenbach A, Krieger N, Strand D, Blencke S, Morbitzer M, et al. Identification and characterization of amphiphysin II as a novel cellular interaction partner of the hepatitis C virus NS5A protein. J Gen Virol. 2003;84:555-60 pubmed
  16. Beran R, Serebrov V, Pyle A. The serine protease domain of hepatitis C viral NS3 activates RNA helicase activity by promoting the binding of RNA substrate. J Biol Chem. 2007;282:34913-20 pubmed
  17. Myong S, Bruno M, Pyle A, Ha T. Spring-loaded mechanism of DNA unwinding by hepatitis C virus NS3 helicase. Science. 2007;317:513-6 pubmed
    ..Such repetitive unwinding behavior over a short stretch of duplex may help to keep secondary structures resolved during viral genome replication. ..
  18. 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
  19. 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
  20. 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. ..
  21. Ghosh A, Majumder M, Steele R, Yaciuk P, Chrivia J, Ray R, et al. Hepatitis C virus NS5A protein modulates transcription through a novel cellular transcription factor SRCAP. J Biol Chem. 2000;275:7184-8 pubmed
    ..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. ..
  22. Carrère Kremer S, Montpellier Pala C, Cocquerel L, Wychowski C, Penin F, Dubuisson J. Subcellular localization and topology of the p7 polypeptide of hepatitis C virus. J Virol. 2002;76:3720-30 pubmed
    ..Altogether, these data indicate that p7 is a polytopic membrane protein that could have a functional role in several compartments of the secretory pathway. ..
  23. Watashi K, Ishii N, Hijikata M, Inoue D, Murata T, Miyanari Y, et al. Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. Mol Cell. 2005;19:111-22 pubmed
    ..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. ..
  24. McCaffrey K, Boo I, Poumbourios P, Drummer H. Expression and characterization of a minimal hepatitis C virus glycoprotein E2 core domain that retains CD81 binding. J Virol. 2007;81:9584-90 pubmed
    ..Our data provide insights into the E2 structure by suggesting that the three variable regions reside outside a conserved E2 core. ..
  25. StGelais C, Foster T, Verow M, Atkins E, Fishwick C, Rowlands D, et al. Determinants of hepatitis C virus p7 ion channel function and drug sensitivity identified in vitro. J Virol. 2009;83:7970-81 pubmed publisher
    ..Lastly, we identify a region at the p7 carboxy terminus which may act as a specific sensitivity determinant for the drug amantadine. ..
  26. 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. ..
  27. 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. ..
  28. Owsianka A, Patel A. Hepatitis C virus core protein interacts with a human DEAD box protein DDX3. Virology. 1999;257:330-40 pubmed
    ..Their role in RNA metabolism or gene expression is unknown. The significance of core-helicase interaction in HCV replication and pathogenesis is discussed. ..
  29. Meola A, Sbardellati A, Bruni Ercole B, Cerretani M, Pezzanera M, Ceccacci A, et al. Binding of hepatitis C virus E2 glycoprotein to CD81 does not correlate with species permissiveness to infection. J Virol. 2000;74:5933-8 pubmed
    ..These results indicate that the binding of E2 to CD81 is not predictive of an infection-producing interaction between HCV and host cells. ..
  30. Pohlmann S, Zhang J, Baribaud F, Chen Z, Leslie G, Lin G, et al. Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR. J Virol. 2003;77:4070-80 pubmed
    ..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. ..
  31. Gao L, Aizaki H, He J, Lai M. Interactions between viral nonstructural proteins and host protein hVAP-33 mediate the formation of hepatitis C virus RNA replication complex on lipid raft. J Virol. 2004;78:3480-8 pubmed
    ..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. ..
  32. Thoren F, Romero A, Lindh M, Dahlgren C, Hellstrand K. A hepatitis C virus-encoded, nonstructural protein (NS3) triggers dysfunction and apoptosis in lymphocytes: role of NADPH oxidase-derived oxygen radicals. J Leukoc Biol. 2004;76:1180-6 pubmed
  33. 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. ..
  34. 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. ..
  35. 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. ..
  36. Lo S, Selby M, Ou J. Interaction between hepatitis C virus core protein and E1 envelope protein. J Virol. 1996;70:5177-82 pubmed
    ..The implications of these findings on the morphogenesis of the hepatitis C virus virion are discussed. ..
  37. Qadri I, Iwahashi M, Simon F. Hepatitis C virus NS5A protein binds TBP and p53, inhibiting their DNA binding and p53 interactions with TBP and ERCC3. Biochim Biophys Acta. 2002;1592:193-204 pubmed
    ..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. ..
  38. Tellinghuisen T, Marcotrigiano J, Gorbalenya A, Rice C. The NS5A protein of hepatitis C virus is a zinc metalloprotein. J Biol Chem. 2004;279:48576-87 pubmed
    ..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. ..
  39. Wang C, Gale M, Keller B, Huang H, Brown M, Goldstein J, et al. Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. Mol Cell. 2005;18:425-34 pubmed
    ..The current data indicate that geranylgeranylated FBL2 binds to NS5A in a reaction crucial for HCV RNA replication. ..
  40. 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. ..
  41. 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. ..
  42. Helle F, Goffard A, Morel V, Duverlie G, McKeating J, Keck Z, et al. The neutralizing activity of anti-hepatitis C virus antibodies is modulated by specific glycans on the E2 envelope protein. J Virol. 2007;81:8101-11 pubmed
    ..In conclusion, this work indicates that HCV glycans contribute to the evasion of HCV from the humoral immune response. ..
  43. 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. ..
  44. 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. ..
  45. 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. ..
  46. Gallinari P, Paolini C, Brennan D, Nardi C, Steinkuhler C, De Francesco R. Modulation of hepatitis C virus NS3 protease and helicase activities through the interaction with NS4A. Biochemistry. 1999;38:5620-32 pubmed
    ..Therefore, NS4A appears to uncouple the ATPase/ssRNA binding and RNA unwinding activities associated with NS3. ..
  47. Macdonald A, Mazaleyrat S, McCormick C, Street A, Burgoyne N, Jackson R, et al. 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. J Gen Virol. 2005;86:1035-44 pubmed
    ..It is more likely that they play a role in altering the cellular environment to favour viral persistence. ..
  48. 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. ..
  49. Gouttenoire J, Castet V, Montserret R, Arora N, Raussens V, Ruysschaert J, et al. Identification of a novel determinant for membrane association in hepatitis C virus nonstructural protein 4B. J Virol. 2009;83:6257-68 pubmed publisher
    ..These results provide the first atomic resolution structure of an essential membrane-associated determinant of HCV NS4B. ..
  50. Kolykhalov A, Agapov E, Blight K, Mihalik K, Feinstone S, Rice C. Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA. Science. 1997;277:570-4 pubmed
    ..This work defines the structure of a functional HCV genome RNA and proves that HCV alone is sufficient to cause disease. ..
  51. Dimitrova M, Imbert I, Kieny M, Schuster C. Protein-protein interactions between hepatitis C virus nonstructural proteins. J Virol. 2003;77:5401-14 pubmed
    ..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. ..
  52. Macdonald A, Crowder K, Street A, McCormick C, Harris M. The hepatitis C virus NS5A protein binds to members of the Src family of tyrosine kinases and regulates kinase activity. J Gen Virol. 2004;85:721-9 pubmed
    ..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. ..
  53. 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. ..
  54. Drummer H, Boo I, Poumbourios P. Mutagenesis of a conserved fusion peptide-like motif and membrane-proximal heptad-repeat region of hepatitis C virus glycoprotein E1. J Gen Virol. 2007;88:1144-8 pubmed
    ..Our data suggest that E1 is unlikely to function in an analogous manner to other class II fusion glycoproteins. ..
  55. 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. ..
  56. 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. ..
  57. 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. ..
  58. Drummer H, Boo I, Maerz A, Poumbourios P. 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. J Virol. 2006;80:7844-53 pubmed
    ..These findings indicate that the G436WLAGLFY motif of E2 functions in CD81 binding and in pre- or post-CD81-dependent stages of viral entry. ..
  59. 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. ..
  60. 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. ..
  61. 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. ..
  62. 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. ..
  63. 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. ..
  64. Palomares Jerez F, Nemésio H, Villalain J. The membrane spanning domains of protein NS4B from hepatitis C virus. Biochim Biophys Acta. 2012;1818:2958-66 pubmed publisher
  65. Quintavalle M, Sambucini S, Di Pietro C, De Francesco R, Neddermann P. The alpha isoform of protein kinase CKI is responsible for hepatitis C virus NS5A hyperphosphorylation. J Virol. 2006;80:11305-12 pubmed
    ..Finally, we showed that down-regulation of CKI-alpha attenuates HCV RNA replication. ..
  66. 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...
  67. 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. ..
  68. 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. ..
  69. 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. ..
  70. 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...
  71. Lai C, Jeng K, Machida K, Lai M. Association of hepatitis C virus replication complexes with microtubules and actin filaments is dependent on the interaction of NS3 and NS5A. J Virol. 2008;82:8838-48 pubmed publisher
  72. 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. ..
  73. Spaziani A, Alisi A, Sanna D, Balsano C. Role of p38 MAPK and RNA-dependent protein kinase (PKR) in hepatitis C virus core-dependent nuclear delocalization of cyclin B1. J Biol Chem. 2006;281:10983-9 pubmed
    ..Based on our model, we now show, for the first time, that HCV core expression leads to deregulation of the mitotic checkpoint via a p38/PKR-dependent pathway. ..
  74. 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. ..
  75. 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
  76. 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. ..
  77. 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. ..
  78. 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. ..
  79. 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. ..
  80. Yue M, Deng X, Zhai X, Xu K, Kong J, Zhang J, et al. Th1 and Th2 cytokine profiles induced by hepatitis C virus F protein in peripheral blood mononuclear cells from chronic hepatitis C patients. Immunol Lett. 2013;152:89-95 pubmed publisher
    ..These findings suggest that F protein may contribute to the HCV-associated bias in Th1/Th2 responses of chronic hepatitis C patients including the progress of HCC pathogenesis. ..
  81. 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. ..
  82. 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. ..
  83. 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. ..
  84. Gouttenoire J, Penin F, Moradpour D. Hepatitis C virus nonstructural protein 4B: a journey into unexplored territory. Rev Med Virol. 2010;20:117-29 pubmed publisher
  85. 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. ..
  86. 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...
  87. 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. ..
  88. 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. ..
  89. Chinnaswamy S, Yarbrough I, Palaninathan S, Kumar C, Vijayaraghavan V, Demeler B, et al. A locking mechanism regulates RNA synthesis and host protein interaction by the hepatitis C virus polymerase. J Biol Chem. 2008;283:20535-46 pubmed publisher
    ..Different conformations of the HCV RdRp can thus affect RNA synthesis and interaction with cellular proteins. ..
  90. Phan T, Beran R, Peters C, Lorenz I, Lindenbach B. Hepatitis C virus NS2 protein contributes to virus particle assembly via opposing epistatic interactions with the E1-E2 glycoprotein and NS3-NS4A enzyme complexes. J Virol. 2009;83:8379-95 pubmed publisher
    ..These data reveal a complex network of interactions involving NS2 and other viral structural and nonstructural proteins during virus assembly. ..
  91. 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. ..