FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2010317967> ?p ?o ?g. }

• W2010317967 endingPage "S13" @default.
• W2010317967 startingPage "S3" @default.
• W2010317967 abstract "Hepatitis C virus (HCV) is an important human pathogen that causes hepatitis, liver cirrhosis and hepatocellular carcinoma. It imposes a serious problem to public health in the world as the population of chronically infected HCV patients who are at risk of progressive liver disease is projected to increase significantly in the next decades. However, the arrival of new antiviral molecules is progressively changing the landscape of hepatitis C treatment. The search for new anti-HCV therapies has also been a driving force to better understand how HCV interacts with its host, and major progresses have been made on the various steps of the HCV life cycle. Here, we review the most recent advances in the fast growing knowledge on HCV life cycle and interaction with host factors and pathways. Hepatitis C virus (HCV) is an important human pathogen that causes hepatitis, liver cirrhosis and hepatocellular carcinoma. It imposes a serious problem to public health in the world as the population of chronically infected HCV patients who are at risk of progressive liver disease is projected to increase significantly in the next decades. However, the arrival of new antiviral molecules is progressively changing the landscape of hepatitis C treatment. The search for new anti-HCV therapies has also been a driving force to better understand how HCV interacts with its host, and major progresses have been made on the various steps of the HCV life cycle. Here, we review the most recent advances in the fast growing knowledge on HCV life cycle and interaction with host factors and pathways. Hepatitis C virus (HCV) constitutes a significant health burden worldwide. Indeed, this virus has a high propensity for establishing a chronic infection and it is estimated that 130–170 million people suffer from chronic hepatitis C. In the long-term, this can lead to advanced liver fibrosis, cirrhosis and hepatocellular carcinoma. As a consequence, HCV is the most common indication for liver transplantation in developed countries [[1]Thomas D.L. Global control of hepatitis C: where challenge meets opportunity.Nat Med. 2013; 19: 850-858Crossref PubMed Scopus (112) Google Scholar]. For more than two decades, interferon has been the basis for HCV treatment. Responses to treatment were improved in 1998 by the addition of ribavirin and then in 2001–2002 by linking the interferon molecule to polyethylene glycol [2Manns M.P. McHutchison J.G. Gordon S.C. Rustgi V.K. Shiffman M. Reindollar R. et al.Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.Lancet. 2001; 358: 958-965Abstract Full Text Full Text PDF PubMed Scopus (5305) Google Scholar, 3McHutchison J.G. Gordon S.C. Schiff E.R. Shiffman M.L. Lee W.M. Rustgi V.K. et al.Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group.N Engl J Med. 1998; 339: 1485-1492Crossref PubMed Scopus (3075) Google Scholar, 4Fried M.W. Shiffman M.L. Reddy K.R. Smith C. Marinos G. Goncales Jr., F.L. et al.Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.N Engl J Med. 2002; 347: 975-982Crossref PubMed Scopus (5215) Google Scholar]. Recently, there have been major advances in hepatitis C treatments with the licensing of the first direct-acting antivirals (DAAs) and large numbers of ongoing trials with various DAAs showing high potency, favourable tolerability profile, higher barrier to resistance, shortened treatment duration, and all oral regimen [[5]Pawlotsky J.M. New hepatitis C therapies: the toolbox, strategies, and challenges.Gastroenterology. 2014; 146: 1176-1192Abstract Full Text Full Text PDF PubMed Scopus (181) Google Scholar]. However, there is no vaccine yet available. Discovered in 1989 [[6]Choo Q.-L. Kuo G. Weiner A.J. Overby L.R. Bradley D.W. Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome.Science. 1989; 244: 359-362Crossref PubMed Google Scholar], HCV is a positive sense, single-stranded RNA virus of the Flaviviridae family, which also includes many arthropod-borne human pathogens of the Flavivirus genus such as yellow fever virus, West Nile virus and dengue virus. HCV genome organization is presented in Fig. 1. Together with the GBV-B virus and the recently identified non-primate, rodent and bat hepaciviruses, HCV has been grouped in the Hepacivirus genus [7Drexler J.F. Corman V.M. Muller M.A. Lukashev A.N. Gmyl A. Coutard B. et al.Evidence for novel hepaciviruses in rodents.PLoS Pathog. 2013; 9: e1003438Crossref PubMed Scopus (13) Google Scholar, 8Kapoor A. Simmonds P. Gerold G. Qaisar N. Jain K. Henriquez J.A. et al.Characterization of a canine homolog of hepatitis C virus.Proc Natl Acad Sci U S A. 2011; 108: 11608-11613Crossref PubMed Scopus (106) Google Scholar, 9Kapoor A. Simmonds P. Scheel T.K. Hjelle B. Cullen J.M. Burbelo P.D. et al.Identification of rodent homologs of hepatitis C virus and pegiviruses.mBio. 2013; 4 (e00216-13)Crossref PubMed Scopus (22) Google Scholar, 10Quan P.L. Firth C. Conte J.M. Williams S.H. Zambrana-Torrelio C.M. Anthony S.J. et al.Bats are a major natural reservoir for hepaciviruses and pegiviruses.Proc Natl Acad Sci U S A. 2013; 110: 8194-8199Crossref PubMed Scopus (31) Google Scholar]. HCV isolates have been grouped into seven genotypes and a number of subtypes [[11]Simmonds P. The origin of hepatitis C virus.Curr Top Microbiol Immunol. 2013; 369: 1-15Crossref PubMed Google Scholar] with distinct geographic distributions and sensitivity to interferon-based treatment [12Manns M.P. Wedemeyer H. Cornberg M. Treating viral hepatitis C: efficacy, side effects, and complications.Gut. 2006; 55: 1350-1359Crossref PubMed Scopus (381) Google Scholar, 13Zein N.N. Clinical significance of hepatitis C virus genotypes.Clin Microbiol Rev. 2000; 13: 223-235Crossref PubMed Scopus (407) Google Scholar]. The only true HCV animal model is the chimpanzee, which has been crucial in studies of HCV immunity and pathogenesis [[14]Bukh J. Animal models for the study of hepatitis C virus infection and related liver disease.Gastroenterology. 2012; 142: e1273Abstract Full Text Full Text PDF Scopus (56) Google Scholar]. In addition, human-liver chimeric and genetically modified HCV-permissive mouse models have also been developed [[15]Billerbeck E. de Jong Y. Dorner M. de la Fuente C. Ploss A. Animal models for hepatitis C.Curr Top Microbiol Immunol. 2013; 369: 49-86PubMed Google Scholar]. For a long time, the lack of a cell culture system has been a major obstacle to study the HCV life cycle. However, selectable replicon systems [[16]Lohmann V. Korner F. Koch J. Herian U. Theilmann L. Bartenschlager R. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line.Science. 1999; 285: 110-113Crossref PubMed Scopus (2062) Google Scholar] and retrovirus-based pseudotyped particles [[17]Bartosch B. Dubuisson J. Cosset F.L. Infectious hepatitis C pseudo-particles containing functional E1E2 envelope protein complexes.J Exp Med. 2003; 197: 633-642Crossref PubMed Scopus (744) Google Scholar] have been major tools to understand HCV genomic replication and virus entry, respectively. Finally, since 2005, the full viral life cycle can be investigated with the help of complete viral replication systems [18Lindenbach B.D. Evans M.J. Syder A.J. Wolk B. Tellinghuisen T.L. Liu C.C. et al.Complete replication of hepatitis C virus in cell culture.Science. 2005; 309: 623-626Crossref PubMed Scopus (1487) Google Scholar, 19Wakita T. Pietschmann T. Kato T. Date T. Miyamoto M. Zhao Z. et al.Production of infectious hepatitis C virus in tissue culture from a cloned viral genome.Nat Med. 2005; 11: 791-796Crossref PubMed Scopus (1847) Google Scholar, 20Zhong J. Gastaminza P. Cheng G. Kapadia S. Kato T. Burton D.R. et al.Robust hepatitis C virus infection in vitro.Proc Natl Acad Sci U S A. 2005; 102: 9294-9299Crossref PubMed Scopus (1210) Google Scholar]. It should be noted that these cell culture systems usually use HuH-7-derived hepatoma cells. However, this cell line lacks many features of hepatocytes [[21]Meex S.J. Andreo U. Sparks J.D. Fisher E.A. Huh-7 or HepG2 cells: which is the better model for studying human apolipoprotein-B100 assembly and secretion?.J Lipid Res. 2011; 52: 152-158Crossref PubMed Scopus (42) Google Scholar]. Primary human hepatocytes or human liver slices have therefore been developed to validate some experiments in more physiological models [22Lagaye S. Shen H. Saunier B. Nascimbeni M. Gaston J. Bourdoncle P. et al.Efficient replication of primary or culture hepatitis C virus isolates in human liver slices: a relevant ex vivo model of liver infection.Hepatology. 2012; 56: 861-872Crossref PubMed Scopus (13) Google Scholar, 23Ploss A. Khetani S.R. Jones C.T. Syder A.J. Trehan K. Gaysinskaya V.A. et al.Persistent hepatitis C virus infection in microscale primary human hepatocyte cultures.Proc Natl Acad Sci U S A. 2010; 107: 3141-3145Crossref PubMed Scopus (109) Google Scholar, 24Podevin P. Carpentier A. Pene V. Aoudjehane L. Carriere M. Zaidi S. et al.Production of infectious hepatitis C virus in primary cultures of human adult hepatocytes.Gastroenterology. 2010; 139: 1355-1364Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar]. In this review, we will discuss recent advances in the virology and cell biology of the HCV life cycle.Fig. 1HCV genome and proteins. HCV genome contains a single open reading frame flanked by 5′ and 3′ non-translated regions (NTRs). The 5′ NTR contains an internal ribosome entry site (IRES). After its synthesis, HCV polyprotein is cleaved by viral and host encoded proteases. Cleavage in the N-terminal part of the polyprotein is mediated by cellular signal peptidases as indicated by individual vertical arrows. An additional cleavage removing the carboxy-terminal region of the core protein is mediated by cellular signal peptide peptidase, as indicated by an open arrow. The linked arrows indicate the cleavages by the viral proteases NS2 and NS3/4A. The functions of the individual proteins are indicated at the bottom of the figure.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Despite substantial progress in producing viral particles in cell culture and several biochemical and morphological studies, the structure of the HCV virion remains poorly characterized. This contrasts with the well-characterized flavivirus viral particles. A striking and unique feature of HCV biology is its association with lipoproteins, which exhibit an unusually low buoyant density [25Andre P. Komurian-Pradel F. Deforges S. Perret M. Berland J.L. Sodoyer M. et al.Characterization of low- and very-low-density hepatitis C virus RNA-containing particles.J Virol. 2002; 76: 6919-6928Crossref PubMed Scopus (412) Google Scholar, 26Thomssen R. Bonk S. Propfe C. Heermann K.H. Kochel H.G. Uy A. Association of hepatitis C virus in human sera with beta-lipoprotein.Med Microbiol Immunol. 1992; 181: 293-300Crossref PubMed Scopus (276) Google Scholar, 27Thomssen R. Bonk S. Thiele A. Density heterogeneities of hepatitis C virus in human sera due to the binding of beta-lipoproteins and immunoglobulins.Med Microbiol Immunol. 1993; 182: 329-334Crossref PubMed Scopus (190) Google Scholar]. HCV particles are 50–80 nm in diameter [[28]Catanese M.T. Uryu K. Kopp M. Edwards T.J. Andrus L. Rice W.J. et al.Ultrastructural analysis of hepatitis C virus particles.Proc Natl Acad Sci U S A. 2013; 110: 9505-9510Crossref PubMed Scopus (66) Google Scholar] and contain the single-stranded RNA genome, core and the envelope glycoproteins, E1 and E2 [[29]Vieyres G. Dubuisson J. Pietschmann T. Incorporation of hepatitis C virus e1 and e2 glycoproteins: the keystones on a peculiar virion.Viruses. 2014; 6: 1149-1187Crossref PubMed Scopus (1) Google Scholar]. The HCV genome interacts with the core protein to form the nucleocapsid that is surrounded by a lipid membrane, called the viral envelope, in which the envelope glycoproteins are anchored. Importantly, due to virion association with lipoproteins, apolipoproteins such as apoE, apoB, apoA1, apoC1, apoC2, and apoC3 can also be found in association with HCV particles [25Andre P. Komurian-Pradel F. Deforges S. Perret M. Berland J.L. Sodoyer M. et al.Characterization of low- and very-low-density hepatitis C virus RNA-containing particles.J Virol. 2002; 76: 6919-6928Crossref PubMed Scopus (412) Google Scholar, 28Catanese M.T. Uryu K. Kopp M. Edwards T.J. Andrus L. Rice W.J. et al.Ultrastructural analysis of hepatitis C virus particles.Proc Natl Acad Sci U S A. 2013; 110: 9505-9510Crossref PubMed Scopus (66) Google Scholar, 30Chang K.S. Jiang J. Cai Z. Luo G. Human apolipoprotein E is required for infectivity and production of hepatitis C virus in cell culture.J Virol. 2007; 81: 13783-13793Crossref PubMed Scopus (246) Google Scholar, 31Meunier J.C. Russell R.S. Engle R.E. Faulk K.N. Purcell R.H. Emerson S.U. Apolipoprotein c1 association with hepatitis C virus.J Virol. 2008; 82: 9647-9656Crossref PubMed Scopus (71) Google Scholar, 32Nielsen S.U. Bassendine M.F. Burt A.D. Martin C. Pumeechockchai W. Toms G.L. Association between hepatitis C virus and very-low-density lipoprotein (VLDL)/LDL analyzed in iodixanol density gradients.J Virol. 2006; 80: 2418-2428Crossref PubMed Scopus (219) Google Scholar]. Furthermore, a characterization of cell culture-produced particles indicates that their lipid composition resembles very-low density lipoproteins (VLDL) and low-density lipoproteins (LDL) with cholesteryl esters accounting for almost half of the total HCV lipids [[33]Merz A. Long G. Hiet M.S. Bruegger B. Chlanda P. Andre P. et al.Biochemical and morphological properties of hepatitis C virus particles and determination of their lipidome.J Biol Chem. 2011; 286: 3018-3032Crossref PubMed Scopus (155) Google Scholar]. Electron microscopy analyses of purified infectious virions confirm the pleomorphic nature of HCV particles and show virions with a rather smooth and even surface [[28]Catanese M.T. Uryu K. Kopp M. Edwards T.J. Andrus L. Rice W.J. et al.Ultrastructural analysis of hepatitis C virus particles.Proc Natl Acad Sci U S A. 2013; 110: 9505-9510Crossref PubMed Scopus (66) Google Scholar]. The exact nature of the interactions involved between HCV virion components and the lipoproteins remains undetermined. It has been suggested that the HCV virion could be a hybrid particle composed of a virion moiety and a lipoprotein moiety [[34]Bartenschlager R. Penin F. Lohmann V. Andre P. Assembly of infectious hepatitis C virus particles.Trends Microbiol. 2011; 19: 95-103Abstract Full Text Full Text PDF PubMed Scopus (203) Google Scholar]. However, alternative models have also been suggested, with lipoproteins peripherally associated with canonical viral particles via interaction between apolipoproteins and HCV envelope lipids or proteins [[35]Lindenbach B.D. Virion assembly and release.Curr Top Microbiol Immunol. 2013; 369: 199-218PubMed Google Scholar]. In both particle types, the interaction with lipoproteins could contribute to the shielding of HCV glycoproteins from the host immune response and explain the poor detection or availability of HCV glycoproteins at the virion surface [28Catanese M.T. Uryu K. Kopp M. Edwards T.J. Andrus L. Rice W.J. et al.Ultrastructural analysis of hepatitis C virus particles.Proc Natl Acad Sci U S A. 2013; 110: 9505-9510Crossref PubMed Scopus (66) Google Scholar, 33Merz A. Long G. Hiet M.S. Bruegger B. Chlanda P. Andre P. et al.Biochemical and morphological properties of hepatitis C virus particles and determination of their lipidome.J Biol Chem. 2011; 286: 3018-3032Crossref PubMed Scopus (155) Google Scholar, 36Dao Thi V.L. Granier C. Zeisel M.B. Guerin M. Mancip J. Granio O. et al.Characterization of hepatitis C virus particle sub-populations reveals multiple usage of the scavenger receptor BI for entry steps.J Biol Chem. 2012; 287: 31242-31257Crossref PubMed Scopus (40) Google Scholar]. Importantly, apolipoprotein(s) associated with HCV virion play a role in HCV entry (see below). HCV envelope glycoproteins are the major viral determinants of HCV entry. They indeed play a role in receptor binding and mediate the fusion process between the viral envelope and an endosomal host cell membrane. HCV glycoproteins E1 and E2 are type I transmembrane proteins, which form a non-covalent heterodimer within infected cells, whereas they assemble as large covalent complexes stabilized by disulfide bonds on the viral particle [[37]Vieyres G. Thomas X. Descamps V. Duverlie G. Patel A.H. Dubuisson J. Characterization of the envelope glycoproteins associated with infectious hepatitis C virus.J Virol. 2010; 84: 10159-10168Crossref PubMed Scopus (105) Google Scholar]. Within the E1E2 heterodimer, the E2 glycoprotein has been shown to interact with receptors or co-receptors on target cells [38Pileri P. Uematsu Y. Campagnoli S. Galli G. Falugi F. Petracca R. et al.Binding of hepatitis C virus to CD81.Science. 1998; 282: 938-941Crossref PubMed Scopus (1474) Google Scholar, 39Scarselli E. Ansuini H. Cerino R. Roccasecca R.M. Acali S. Filocamo G. et al.The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus.EMBO J. 2002; 21: 5017-5025Crossref PubMed Scopus (727) Google Scholar]. Based on the hypothesis that the structure of the fusion protein should be conserved within the Flaviviridae family, E2 had also initially been proposed to be the fusion protein responsible for the fusion between HCV envelope and a host-cell membrane [[40]Krey T. d’Alayer J. Kikuti C.M. 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: e1000762Crossref PubMed Scopus (140) Google Scholar]. However, recently published crystal structures of the E2 glycoprotein core domain do not confirm this hypothesis [41Kong L. Giang E. Nieusma T. Kadam R.U. Cogburn K.E. Hua Y. et al.Hepatitis C virus E2 envelope glycoprotein core structure.Science. 2013; 342: 1090-1094Crossref PubMed Scopus (96) Google Scholar, 42Khan A.G. Whidby J. Miller M.T. Scarborough H. Zatorski A.V. Cygan A. et al.Structure of the core ectodomain of the hepatitis C virus envelope glycoprotein 2.Nature. 2014; 509: 381-384Crossref PubMed Scopus (70) Google Scholar]. Furthermore, instead of forming an elongated shape, composed of three domains as previously predicted [[40]Krey T. d’Alayer J. Kikuti C.M. 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: e1000762Crossref PubMed Scopus (140) Google Scholar], E2 forms a compact globular structure distinct from any known viral fusion protein. Interestingly, the masking of neutralizing epitopes by glycans and the definition of the CD81 binding site in this new structure confirms previous experimental results [43Helle F. Vieyres G. Elkrief L. Popescu C.I. Wychowski C. Descamps V. et al.Role of N-linked glycans in the functions of HCV envelope proteins incorporated into infectious virions.J Virol. 2010; 84: 11905-11915Crossref PubMed Scopus (65) Google Scholar, 44Owsianka A.M. Timms J.M. Tarr A.W. Brown R.J. Hickling T.P. 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: 8695-8704Crossref PubMed Scopus (144) Google Scholar]. Furthermore, these new data strongly suggest that E1 should be the fusion protein or, at least, a fusion partner of an E1E2 fusion complex formed upon conformational rearrangements [45Douam F. Dao Thi V.L. Maurin G. Fresquet J. Mompelat D. Zeisel M.B. et al.Critical interaction between E1 and E2 glycoproteins determines binding and fusion properties of hepatitis C virus during cell entry.Hepatology. 2014; 59: 776-788Crossref PubMed Scopus (26) Google Scholar, 46Lavillette D. Pecheur E.I. 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: 8752-8765Crossref PubMed Scopus (115) Google Scholar]. Viral entry plays an important role for hepatocyte tropism of HCV. During a primary infection, HCV particles are transported by the blood stream and come into contact with hepatocytes after crossing the fenestrated endothelium of the liver sinusoids. In the space of Disse, virions have direct contact with the basolateral surface of hepatocytes. This allows them to interact with attachment factors and receptors on the surface of these cells. Initial attachment of HCV particles onto hepatocytes is mediated by the heparan sulfate proteoglycan syndecan-1 or syndecan-4 [47Lefevre M. Felmlee D.J. Parnot M. Baumert T.F. Schuster C. Syndecan 4 is involved in mediating HCV entry through interaction with lipoviral particle-associated apolipoprotein E.PLoS One. 2014; 9: e95550Crossref PubMed Google Scholar, 48Shi Q. Jiang J. Luo G. Syndecan-1 serves as the major receptor for attachment of hepatitis C virus to the surfaces of hepatocytes.J Virol. 2013; 87: 6866-6875Crossref PubMed Scopus (29) Google Scholar] or by the scavenger receptor B1 (SRB1) [[36]Dao Thi V.L. Granier C. Zeisel M.B. Guerin M. Mancip J. Granio O. et al.Characterization of hepatitis C virus particle sub-populations reveals multiple usage of the scavenger receptor BI for entry steps.J Biol Chem. 2012; 287: 31242-31257Crossref PubMed Scopus (40) Google Scholar], which depends on virion density. It was initially thought that HCV glycoproteins are responsible for virion binding to heparan sulfate proteoglycans [[49]Barth H. Schafer C. Adah M.I. Zhang F. Linhardt R.J. Toyoda H. et al.Cellular binding of hepatitis C virus envelope glycoprotein E2 requires cell surface heparan sulfate.J Biol Chem. 2003; 278: 41003-41012Crossref PubMed Scopus (300) Google Scholar] or SRB1 [[39]Scarselli E. Ansuini H. Cerino R. Roccasecca R.M. Acali S. Filocamo G. et al.The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus.EMBO J. 2002; 21: 5017-5025Crossref PubMed Scopus (727) Google Scholar]. However, more recent data suggest that ApoE, rather than HCV glycoproteins themselves, could be involved in this initial contact [36Dao Thi V.L. Granier C. Zeisel M.B. Guerin M. Mancip J. Granio O. et al.Characterization of hepatitis C virus particle sub-populations reveals multiple usage of the scavenger receptor BI for entry steps.J Biol Chem. 2012; 287: 31242-31257Crossref PubMed Scopus (40) Google Scholar, 50Jiang J. Wu X. Tang H. Luo G. Apolipoprotein E mediates attachment of clinical hepatitis C virus to hepatocytes by binding to cell surface heparan sulfate proteoglycan receptors.PLoS One. 2013; 8: e67982Crossref PubMed Scopus (19) Google Scholar]. Due to HCV particle interaction with lipoproteins, the LDL receptor (LDLR) has also been proposed to play a role in the early phase of HCV entry [[51]Agnello V. Abel G. Elfahal M. Knight G.B. Zhang Q.-X. Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor.Proc Natl Acad Sci U S A. 1999; 96: 12766-12771Crossref PubMed Scopus (675) Google Scholar]. However, HCV-LDLR interaction seems to involve a non-productive entry pathway that can potentially lead to viral particle degradation [[52]Albecka A. Belouzard S. de Beeck A.O. Descamps V. Goueslain L. Bertrand-Michel J. et al.Role of low-density lipoprotein receptor in the hepatitis C virus life cycle.Hepatology. 2012; 55: 998-1007Crossref PubMed Scopus (69) Google Scholar]. After the initial attachment to the cell surface, the following steps of HCV entry are only partially understood and they involve a series of specific cellular entry factors (Fig. 2). It emerges that the coordinated action of at least four major cellular factors is essential for HCV entry. They include SRB1 [[39]Scarselli E. Ansuini H. Cerino R. Roccasecca R.M. Acali S. Filocamo G. et al.The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus.EMBO J. 2002; 21: 5017-5025Crossref PubMed Scopus (727) Google Scholar], tetraspanin CD81 [[38]Pileri P. Uematsu Y. Campagnoli S. Galli G. Falugi F. Petracca R. et al.Binding of hepatitis C virus to CD81.Science. 1998; 282: 938-941Crossref PubMed Scopus (1474) Google Scholar] and tight-junction proteins claudin-1 (CLDN1) [[53]Evans M.J. von Hahn T. Tscherne D.M. Syder A.J. Panis M. Wolk B. et al.Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry.Nature. 2007; 446: 801-805Crossref PubMed Scopus (725) Google Scholar], and occludin (OCLN) [[54]Ploss A. Evans M.J. Gaysinskaya V.A. Panis M. You H. de Jong Y.P. et al.Human occludin is a hepatitis C virus entry factor required for infection of mouse cells.Nature. 2009; 457: 882-886Crossref PubMed Scopus (518) Google Scholar]. Due to its dual interaction with HCV glycoprotein E2 and lipoproteins, SRB1 could be a first entry factor, interacting with the virion after initial cell attachment. The role of SRB1 in HCV entry was first suggested by its ability to mediate E2 binding and the hypervariable region 1 (HVR1) of E2 is essential for this interaction [[39]Scarselli E. Ansuini H. Cerino R. Roccasecca R.M. Acali S. Filocamo G. et al.The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus.EMBO J. 2002; 21: 5017-5025Crossref PubMed Scopus (727) Google Scholar]. However, as above discussed, SRB1 also seems to contribute to virus attachment through interaction with virus-associated lipoproteins [36Dao Thi V.L. Granier C. Zeisel M.B. Guerin M. Mancip J. Granio O. et al.Characterization of hepatitis C virus particle sub-populations reveals multiple usage of the scavenger receptor BI for entry steps.J Biol Chem. 2012; 287: 31242-31257Crossref PubMed Scopus (40) Google Scholar, 55Maillard P. Huby T. Andreo U. Moreau M. Chapman J. Budkowska A. The interaction of natural hepatitis C virus with human scavenger receptor SR-BI/Cla1 is mediated by ApoB-containing lipoproteins.FASEB J. 2006; 20: 735-737Crossref PubMed Scopus (0) Google Scholar] and HCV mutants, harbouring HVR1 deletion or mutation that prevent E2 binding to SRB1, remain dependent on SRB1 for entry into cells [[36]Dao Thi V.L. Granier C. Zeisel M.B. Guerin M. Mancip J. Granio O. et al.Characterization of hepatitis C virus particle sub-populations reveals multiple usage of the scavenger receptor BI for entry steps.J Biol Chem. 2012; 287: 31242-31257Crossref PubMed Scopus (40) Google Scholar]. One elegant hypothesis is that SRB1, through its lipid transfer activity, could modify the lipid composition of the lipoprotein moiety of the virion, which would lead to a better exposure of the CD81 binding site on E2 glycoprotein, as suggested by the observation that SRB1 mediates a post-binding event important for productive viral entry [36Dao Thi V.L. Granier C. Zeisel M.B. Guerin M. Mancip J. Granio O. et al.Characterization of hepatitis C virus particle sub-populations reveals multiple usage of the scavenger receptor BI for entry steps.J Biol Chem. 2012; 287: 31242-31257Crossref PubMed Scopus (40) Google Scholar, 56Zahid M.N. Turek M. Xiao F. Thi V.L. Guerin M. Fofana I. et al.The postbinding activity of scavenger receptor class B type I mediates initiation of hepatitis C virus infection and viral dissemination.Hepatology. 2013; 57: 492-504Crossref PubMed Scopus (20) Google Scholar]. Alternatively, SRB1 interaction with HVR1 could also unmask the CD81 binding site of E2, as suggested by the reduced dependency on SRB1 of HVR1-deleted mutant viruses [57Bankwitz D. Steinmann E. Bitzegeio J. Ciesek S. Friesland M. Herrmann E. et al.Hepatitis C virus hypervariable region 1 modulates receptor interactions, conceals the CD81 binding site, and protects conserved neutralizing epitopes.J Virol. 2010; 84: 5751-5763Crossref PubMed Scopus (96) Google Scholar, 58Dreux M. Dao Thi V.L. Fresquet J. Guerin M. Julia Z. Verney G. et al.Receptor complementation and mutagenesis reveal SR-BI as an essential HCV entry factor and functionally imply its intra- and extra-cellular domains.PLoS Pathog. 2009; 5: e1000310Crossref PubMed Scopus (70) Google Scholar, 59Prentoe J. Jensen T.B. Meuleman P. Serre S.B. Scheel T.K. Leroux-Roels G. et al.Hypervariable region 1 differentially impacts viability of hepatitis C virus strains of genotypes 1 to 6 and impairs virus neutralization.J Virol. 2011; 85: 2224-2234Crossref PubMed Scopus (67) Google Scholar]. Whatever the mechanism involved, HCV virion seems to be primed to interact with CD81 after SRB1 binding. Among HCV entry factors, the tetraspanin CD81 is undoubtedly a key player in the HCV lifecycle [[60]Feneant L. Levy S. Cocquerel L. CD81 and hepatitis C virus (HCV) infection.Viruses. 2014; 6: 535-572Crossref PubMed Google Scholar]. Amino acid residues involved in CD81 binding are located at the surface of the core of E2 protein [[41]Kong L. Giang E. Nieusma T. Kadam R.U. Cogburn K.E. Hua Y. et al.Hepatitis C virus E2 envelope glycoprotein core structure.Science. 2013; 342: 1090-1094Crossref PubMed Scopus (96) Google Scholar]. This interaction seems to prime HCV envelope proteins for low pH-dependent fusion [[61]Sharma N.R. Mateu G. Dreux M. Grakoui A. Cosset F.L. Melikyan G.B. Hepatitis C virus is primed by CD81 protein for low pH-dependent fusion.J Biol Chem. 2011; 286: 30361-30376Crossref PubMed Scopus (40) Google Scholar]. CD81 is" @default.
• W2010317967 created "2016-06-24" @default.
• W2010317967 creator A5006682801 @default.
• W2010317967 creator A5087727909 @default.
• W2010317967 date "2014-11-01" @default.
• W2010317967 modified "2023-10-17" @default.
• W2010317967 title "Virology and cell biology of the hepatitis C virus life cycle – An update" @default.
• W2010317967 cites W1530729111 @default.
• W2010317967 cites W1582903724 @default.
• W2010317967 cites W1586053156 @default.
• W2010317967 cites W1635062911 @default.
• W2010317967 cites W1966021812 @default.
• W2010317967 cites W1967946955 @default.
• W2010317967 cites W1967977640 @default.
• W2010317967 cites W1968376947 @default.
• W2010317967 cites W1969720994 @default.
• W2010317967 cites W1970602702 @default.
• W2010317967 cites W1970828145 @default.
• W2010317967 cites W1971435934 @default.
• W2010317967 cites W1972359004 @default.
• W2010317967 cites W1977036616 @default.
• W2010317967 cites W1978016645 @default.
• W2010317967 cites W1980467489 @default.
• W2010317967 cites W1982315879 @default.
• W2010317967 cites W1983251711 @default.
• W2010317967 cites W1984595411 @default.
• W2010317967 cites W1984646698 @default.
• W2010317967 cites W1986505810 @default.
• W2010317967 cites W1986551392 @default.
• W2010317967 cites W1987199366 @default.
• W2010317967 cites W1987689660 @default.
• W2010317967 cites W1988708890 @default.
• W2010317967 cites W1989242471 @default.
• W2010317967 cites W1992601225 @default.
• W2010317967 cites W1993170858 @default.
• W2010317967 cites W1993809579 @default.
• W2010317967 cites W1997385930 @default.
• W2010317967 cites W1998256358 @default.
• W2010317967 cites W1998502206 @default.
• W2010317967 cites W1998833977 @default.
• W2010317967 cites W2000927719 @default.
• W2010317967 cites W2001558817 @default.
• W2010317967 cites W2002145540 @default.
• W2010317967 cites W2003579943 @default.
• W2010317967 cites W2006309458 @default.
• W2010317967 cites W2007013372 @default.
• W2010317967 cites W2009429471 @default.
• W2010317967 cites W2014060674 @default.
• W2010317967 cites W2015489330 @default.
• W2010317967 cites W2018419706 @default.
• W2010317967 cites W2019804310 @default.
• W2010317967 cites W2022557944 @default.
• W2010317967 cites W2022741181 @default.
• W2010317967 cites W2022869504 @default.
• W2010317967 cites W2025491143 @default.
• W2010317967 cites W2026051181 @default.
• W2010317967 cites W2027545702 @default.
• W2010317967 cites W2031602764 @default.
• W2010317967 cites W2033110360 @default.
• W2010317967 cites W2035669429 @default.
• W2010317967 cites W2036306822 @default.
• W2010317967 cites W2036761416 @default.
• W2010317967 cites W2037798847 @default.
• W2010317967 cites W2037999529 @default.
• W2010317967 cites W2040154453 @default.
• W2010317967 cites W2041059625 @default.
• W2010317967 cites W2043080047 @default.
• W2010317967 cites W2044193462 @default.
• W2010317967 cites W2044279872 @default.
• W2010317967 cites W2045065319 @default.
• W2010317967 cites W2046984465 @default.
• W2010317967 cites W2048974214 @default.
• W2010317967 cites W2048989237 @default.
• W2010317967 cites W2049016083 @default.
• W2010317967 cites W2050028384 @default.
• W2010317967 cites W2051481258 @default.
• W2010317967 cites W2053406561 @default.
• W2010317967 cites W2054862747 @default.
• W2010317967 cites W2055090323 @default.
• W2010317967 cites W2057822166 @default.
• W2010317967 cites W2057842103 @default.
• W2010317967 cites W2057967679 @default.
• W2010317967 cites W2059670505 @default.
• W2010317967 cites W2061343285 @default.
• W2010317967 cites W2061517295 @default.
• W2010317967 cites W2062370188 @default.
• W2010317967 cites W2064396919 @default.
• W2010317967 cites W2064526034 @default.
• W2010317967 cites W2064778609 @default.
• W2010317967 cites W2067891918 @default.
• W2010317967 cites W2067933199 @default.
• W2010317967 cites W2068411103 @default.
• W2010317967 cites W2069463866 @default.
• W2010317967 cites W2069597046 @default.
• W2010317967 cites W2072109464 @default.
• W2010317967 cites W2075147482 @default.
• W2010317967 cites W2075557556 @default.
• W2010317967 cites W2076941967 @default.

• next