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Semin Liver Dis 2010; 30(4): 333-347
DOI: 10.1055/s-0030-1267535
© Thieme Medical PublishersDOI: 10.1055/s-0030-1267535
New Insights into Structure and Replication of the Hepatitis C Virus and Clinical Implications
Weitere Informationen
Publikationsverlauf
Publikationsdatum:
19. Oktober 2010 (online)
ABSTRACT
With the advent of efficient systems to propagate the hepatitis C virus (HCV) in cultured cells important new discoveries have been made. For instance, several molecules required for HCV infection of hepatocytes have been identified and first insights into the entry pathway have been gained. Ribonucleic acid (RNA) replication and virion assembly were found to be tightly linked to lipid metabolism and numerous host factors contributing to viral replication have been identified. Some of them such as cyclophilin A or microRNA-122 are attractive targets for antiviral therapy as are the viral serine-type protease residing in nonstructural protein 3 (NS3) and the NS5B RNA-dependent RNA polymerase. More recently, the viral phosphoprotein NS5A emerged as an additional and very promising target for selective therapy. These results illustrate the great progress that has been made in the HCV field and how this knowledge can be used to devise innovative strategies to counteract this pathogen.
KEYWORDS
STAT-C - NS3 protease - NS5A protein - NS5B RNA-dependent RNA polymerase - miR-122 - cyclophilin A
REFERENCES
- 1 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(4902) 359-362
- 2 Kuo G, Choo Q L, Alter H J et al.. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science. 1989; 244(4902) 362-364
- 3 Shepard C W, Finelli L, Alter M J. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis. 2005; 5(9) 558-567
- 4 Seeff L B. Natural history of chronic hepatitis C. Hepatology. 2002; 36(5, Suppl 1) S35-S46
- 5 Wiese M, Berr F, Lafrenz M, Porst H, Oesen U. Low frequency of cirrhosis in a hepatitis C (genotype 1b) single-source outbreak in Germany: a 20-year multicenter study. Hepatology. 2000; 32(1) 91-96
- 6 Hoofnagle J H. Course and outcome of hepatitis C. Hepatology. 2002; 36(5, Suppl 1) S21-S29
- 7 Poynard T, Yuen M F, Ratziu V, Lai C L. Viral hepatitis C. Lancet. 2003; 362(9401) 2095-2100
- 8 Gerlach J T, Diepolder H M, Zachoval R et al.. Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. Gastroenterology. 2003; 125(1) 80-88
- 9 Micallef J M, Kaldor J M, Dore G J. Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies. J Viral Hepat. 2006; 13(1) 34-41
- 10 Alter M J. Epidemiology of hepatitis C. Eur J Gastroenterol Hepatol. 1996; 8(4) 319-323
- 11 Alter M J. Epidemiology of hepatitis C virus infection. World J Gastroenterol. 2007; 13(17) 2436-2441
- 12 Ge D, Fellay J, Thompson A J et al.. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009; 461(7262) 399-401
- 13 Tanaka Y, Nishida N, Sugiyama M et al.. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009; 41(10) 1105-1109
- 14 Suppiah V, Moldovan M, Ahlenstiel G et al.. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet. 2009; 41(10) 1100-1104
- 15 François C, Castelain S, Duverlie G, Capron D, Nguyen-Khac E. Optimizing the treatment of chronic viral hepatitis C. Expert Rev Gastroenterol Hepatol. 2009; 3(6) 607-613
- 16 Feld J J, Hoofnagle J H. Mechanism of action of interferon and ribavirin in treatment of hepatitis C. Nature. 2005; 436(7053) 967-972
- 17 Williams R. Global challenges in liver disease. Hepatology. 2006; 44(3) 521-526
- 18 Pham T N, King D, Macparland S A et al.. Hepatitis C virus replicates in the same immune cell subsets in chronic hepatitis C and occult infection. Gastroenterology. 2008; 134(3) 812-822
- 19 Bukh J. A critical role for the chimpanzee model in the study of hepatitis C. Hepatology. 2004; 39(6) 1469-1475
- 20 Lanford R E, Bigger C, Bassett S, Klimpel G. The chimpanzee model of hepatitis C virus infections. ILAR J. 2001; 42(2) 117-126
- 21 Lindenbach B D, Meuleman P, Ploss A et al.. Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. Proc Natl Acad Sci U S A. 2006; 103(10) 3805-3809
- 22 Bissig K D, Wieland S F, Tran P et al.. Human liver chimeric mice provide a model for hepatitis B and C virus infection and treatment. J Clin Invest. 2010; 120(3) 924-930
- 23 Meuleman P, Libbrecht L, De Vos R et al.. Morphological and biochemical characterization of a human liver in a uPA-SCID mouse chimera. Hepatology. 2005; 41(4) 847-856
- 24 Mercer D F, Schiller D E, Elliott J F et al.. Hepatitis C virus replication in mice with chimeric human livers. Nat Med. 2001; 7(8) 927-933
- 25 Kuiken C, Simmonds P. Nomenclature and numbering of the hepatitis C virus. Methods Mol Biol. 2009; 510 33-53
- 26 Dazert E, Neumann-Haefelin C, Bressanelli S et al.. Loss of viral fitness and cross-recognition by CD8 + T cells limit HCV escape from a protective HLA-B27-restricted human immune response. J Clin Invest. 2009; 119(2) 376-386
- 27 Kieffer T L, Kwong A D, Picchio G R. Viral resistance to specifically targeted antiviral therapies for hepatitis C (STAT-Cs). J Antimicrob Chemother. 2010; 65(2) 202-212
- 28 Bartenschlager R, Frese M, Pietschmann T. Novel insights into hepatitis C virus replication and persistence. Adv Virus Res. 2004; 63 71-180
- 29 Lukavsky P J. Structure and function of HCV IRES domains. Virus Res. 2009; 139(2) 166-171
- 30 Friebe P, Lohmann V, Krieger N, Bartenschlager R. Sequences in the 5′ nontranslated region of hepatitis C virus required for RNA replication. J Virol. 2001; 75(24) 12047-12057
- 31 Jopling C L, Yi M, Lancaster A M, Lemon S M, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science. 2005; 309(5740) 1577-1581
- 32 Henke J I, Goergen D, Zheng J et al.. microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J. 2008; 27(24) 3300-3310
- 33 Jangra R K, Yi M, Lemon S M. Regulation of hepatitis C virus translation and infectious virus production by the microRNA miR-122. J Virol. 2010; 84(13) 6615-6625
- 34 Jopling C L, Schütz S, Sarnow P. Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell Host Microbe. 2008; 4(1) 77-85
- 35 Lanford R E, Hildebrandt-Eriksen E S, Petri A et al.. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science. 2010; 327(5962) 198-201
- 36 Yanagi M, St Claire M, Emerson S U, Purcell R H, Bukh J. In vivo analysis of the 3′ untranslated region of the hepatitis C virus after in vitro mutagenesis of an infectious cDNA clone. Proc Natl Acad Sci U S A. 1999; 96(5) 2291-2295
- 37 Friebe P, Bartenschlager R. Genetic analysis of sequences in the 3′ nontranslated region of hepatitis C virus that are important for RNA replication. J Virol. 2002; 76(11) 5326-5338
- 38 Kolykhalov A A, Feinstone S M, Rice C M. Identification of a highly conserved sequence element at the 3′ terminus of hepatitis C virus genome RNA. J Virol. 1996; 70(6) 3363-3371
- 39 Tanaka T, Kato N, Cho M J, Sugiyama K, Shimotohno K. Structure of the 3′ terminus of the hepatitis C virus genome. J Virol. 1996; 70(5) 3307-3312
- 40 Song Y, Friebe P, Tzima E, Jünemann C, Bartenschlager R, Niepmann M. The hepatitis C virus RNA 3′-untranslated region strongly enhances translation directed by the internal ribosome entry site. J Virol. 2006; 80(23) 11579-11588
- 41 You S, Stump D D, Branch A D, Rice C M. A cis-acting replication element in the sequence encoding the NS5B RNA-dependent RNA polymerase is required for hepatitis C virus RNA replication. J Virol. 2004; 78(3) 1352-1366
- 42 Friebe P, Boudet J, Simorre J P, Bartenschlager R. Kissing-loop interaction in the 3′ end of the hepatitis C virus genome essential for RNA replication. J Virol. 2005; 79(1) 380-392
- 43 Diviney S, Tuplin A, Struthers M et al.. A hepatitis C virus cis-acting replication element forms a long-range RNA-RNA interaction with upstream RNA sequences in NS5B. J Virol. 2008; 82(18) 9008-9022
- 44 Moradpour D, Penin F, Rice C M. Replication of hepatitis C virus. Nat Rev Microbiol. 2007; 5(6) 453-463
- 45 Hijikata M, Kato N, Ootsuyama Y, Nakagawa M, Shimotohno K. Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro processing analysis. Proc Natl Acad Sci U S A. 1991; 88(13) 5547-5551
- 46 McLauchlan J, Lemberg M K, Hope G, Martoglio B. Intramembrane proteolysis promotes trafficking of hepatitis C virus core protein to lipid droplets. EMBO J. 2002; 21(15) 3980-3988
- 47 Miyanari Y, Atsuzawa K, Usuda N et al.. The lipid droplet is an important organelle for hepatitis C virus production. Nat Cell Biol. 2007; 9(9) 1089-1097
- 48 Boulant S, Montserret R, Hope R G et al.. Structural determinants that target the hepatitis C virus core protein to lipid droplets. J Biol Chem. 2006; 281(31) 22236-22247
- 49 Eng F J, Walewski J L, Klepper A L et al.. Internal initiation stimulates production of p8 minicore, a member of a newly discovered family of hepatitis C virus core protein isoforms. J Virol. 2009; 83(7) 3104-3114
- 50 Branch A D, Stump D D, Gutierrez J A, Eng F, Walewski J L. The hepatitis C virus alternate reading frame (ARF) and its family of novel products: the alternate reading frame protein/F-protein, the double-frameshift protein, and others. Semin Liver Dis. 2005; 25(1) 105-117
- 51 Vassilaki N, Mavromara P. The HCV ARFP/F/core + 1 protein: production and functional analysis of an unconventional viral product. IUBMB Life. 2009; 61(7) 739-752
- 52 Ratinier M, Boulant S, Crussard S, McLauchlan J, Lavergne J P. Subcellular localizations of the hepatitis C virus alternate reading frame proteins. Virus Res. 2009; 139(1) 106-110
- 53 Dubuisson J. Folding, assembly and subcellular localization of hepatitis C virus glycoproteins. Curr Top Microbiol Immunol. 2000; 242 135-148
- 54 Dubuisson J, Rice C M. Hepatitis C virus glycoprotein folding: disulfide bond formation and association with calnexin. J Virol. 1996; 70(2) 778-786
- 55 Choukhi A, Ung S, Wychowski C, Dubuisson J. Involvement of endoplasmic reticulum chaperones in the folding of hepatitis C virus glycoproteins. J Virol. 1998; 72(5) 3851-3858
- 56 Merola M, Brazzoli M, Cocchiarella F et al.. Folding of hepatitis C virus E1 glycoprotein in a cell-free system. J Virol. 2001; 75(22) 11205-11217
- 57 Michalak J P, Wychowski C, Choukhi A et al.. Characterization of truncated forms of hepatitis C virus glycoproteins. J Gen Virol. 1997; 78(Pt 9) 2299-2306
- 58 Dubuisson J, Hsu H H, Cheung R C, Greenberg H B, Russell D G, Rice C M. Formation and intracellular localization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia and Sindbis viruses. J Virol. 1994; 68(10) 6147-6160
- 59 Ralston R, Thudium K, Berger K et al.. Characterization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia viruses. J Virol. 1993; 67(11) 6753-6761
- 60 Deleersnyder V, Pillez A, Wychowski C et al.. Formation of native hepatitis C virus glycoprotein complexes. J Virol. 1997; 71(1) 697-704
- 61 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(8) 3720-3730
- 62 Luik P, Chew C, Aittoniemi J et al.. The 3-dimensional structure of a hepatitis C virus p7 ion channel by electron microscopy. Proc Natl Acad Sci U S A. 2009; 106(31) 12712-12716
- 63 Steinmann E, Penin F, Kallis S, Patel A H, Bartenschlager R, Pietschmann T. Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions. PLoS Pathog. 2007; 3(7) e103
- 64 Hijikata M, Mizushima H, Akagi T et al.. Two distinct proteinase activities required for the processing of a putative nonstructural precursor protein of hepatitis C virus. J Virol. 1993; 67(8) 4665-4675
- 65 Lorenz I C, Marcotrigiano J, Dentzer T G, Rice C M. Structure of the catalytic domain of the hepatitis C virus NS2-3 protease. Nature. 2006; 442(7104) 831-835
- 66 Lohmann V, Körner F, Koch J O, Herian U, Theilmann L, Bartenschlager R. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science. 1999; 285(5424) 110-113
- 67 Jones C T, Murray C L, Eastman D K, Tassello J, Rice C M. Hepatitis C virus p7 and NS2 proteins are essential for production of infectious virus. J Virol. 2007; 81(16) 8374-8383
- 68 Jirasko V, Montserret R, Appel N et al.. Structural and functional characterization of nonstructural protein 2 for its role in hepatitis C virus assembly. J Biol Chem. 2008; 283(42) 28546-28562
- 69 Bartenschlager R, Ahlborn-Laake L, Mous J, Jacobsen H. Nonstructural protein 3 of the hepatitis C virus encodes a serine-type proteinase required for cleavage at the NS3/4 and NS4/5 junctions. J Virol. 1993; 67(7) 3835-3844
- 70 Grakoui A, McCourt D W, Wychowski C, Feinstone S M, Rice C M. A second hepatitis C virus-encoded proteinase. Proc Natl Acad Sci U S A. 1993; 90(22) 10583-10587
- 71 Kolykhalov A A, Mihalik K, Feinstone S M, Rice C M. Hepatitis C virus-encoded enzymatic activities and conserved RNA elements in the 3′ nontranslated region are essential for virus replication in vivo. J Virol. 2000; 74(4) 2046-2051
- 72 Ma Y, Yates J, Liang Y, Lemon S M, Yi M. NS3 helicase domains involved in infectious intracellular hepatitis C virus particle assembly. J Virol. 2008; 82(15) 7624-7639
- 73 Phan T, Beran R K, Peters C, Lorenz I C, Lindenbach B D. 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(17) 8379-8395
- 74 Failla C, Tomei L, De Francesco R. Both NS3 and NS4A are required for proteolytic processing of hepatitis C virus nonstructural proteins. J Virol. 1994; 68(6) 3753-3760
- 75 Bartenschlager R, Ahlborn-Laake L, Mous J, Jacobsen H. Kinetic and structural analyses of hepatitis C virus polyprotein processing. J Virol. 1994; 68(8) 5045-5055
- 76 Wölk B, Sansonno D, Kräusslich H G et al.. Subcellular localization, stability, and trans-cleavage competence of the hepatitis C virus NS3-NS4A complex expressed in tetracycline-regulated cell lines. J Virol. 2000; 74(5) 2293-2304
- 77 Li K, Foy E, Ferreon J C et al.. Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci U S A. 2005; 102(8) 2992-2997
- 78 Meylan E, Curran J, Hofmann K et al.. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature. 2005; 437(7062) 1167-1172
- 79 Lamarre D, Anderson P C, Bailey M et al.. An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus. Nature. 2003; 426(6963) 186-189
- 80 Lundin M, Monné M, Widell A, Von Heijne G, Persson M A. Topology of the membrane-associated hepatitis C virus protein NS4B. J Virol. 2003; 77(9) 5428-5438
- 81 Gouttenoire J, Penin F, Moradpour D. Hepatitis C virus nonstructural protein 4B: a journey into unexplored territory. Rev Med Virol. 2010; 20(2) 117-129
- 82 Egger D, Wölk B, Gosert R et al.. Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex. J Virol. 2002; 76(12) 5974-5984
- 83 Einav S, Gerber D, Bryson P D et al.. Discovery of a hepatitis C target and its pharmacological inhibitors by microfluidic affinity analysis. Nat Biotechnol. 2008; 26(9) 1019-1027
- 84 Einav S, Elazar M, Danieli T, Glenn J S. A nucleotide binding motif in hepatitis C virus (HCV) NS4B mediates HCV RNA replication. J Virol. 2004; 78(20) 11288-11295
- 85 Lohmann V, Hoffmann S, Herian U, Penin F, Bartenschlager R. Viral and cellular determinants of hepatitis C virus RNA replication in cell culture. J Virol. 2003; 77(5) 3007-3019
- 86 Kaneko T, Tanji Y, Satoh S et al.. Production of two phosphoproteins from the NS5A region of the hepatitis C viral genome. Biochem Biophys Res Commun. 1994; 205(1) 320-326
- 87 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(22) 11305-11312
- 88 Tellinghuisen T L, Foss K L, Treadaway J. Regulation of hepatitis C virion production via phosphorylation of the NS5A protein. PLoS Pathog. 2008; 4(3) e1000032
- 89 Appel N, Pietschmann T, Bartenschlager R. Mutational analysis of hepatitis C virus nonstructural protein 5A: potential role of differential phosphorylation in RNA replication and identification of a genetically flexible domain. J Virol. 2005; 79(5) 3187-3194
- 90 Evans M J, Rice C M, Goff S P. Phosphorylation of hepatitis C virus nonstructural protein 5A modulates its protein interactions and viral RNA replication. Proc Natl Acad Sci U S A. 2004; 101(35) 13038-13043
- 91 Neddermann P, Quintavalle M, Di Pietro C et al.. Reduction of hepatitis C virus NS5A hyperphosphorylation by selective inhibition of cellular kinases activates viral RNA replication in cell culture. J Virol. 2004; 78(23) 13306-13314
- 92 Gao L, Aizaki H, He J W, Lai M 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(7) 3480-3488
- 93 Tellinghuisen T L, Marcotrigiano J, Rice C M. Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase. Nature. 2005; 435(7040) 374-379
- 94 Love R A, Brodsky O, Hickey M J, Wells P A, Cronin C N. Crystal structure of a novel dimeric form of NS5A domain I protein from hepatitis C virus. J Virol. 2009; 83(9) 4395-4403
- 95 Tellinghuisen T L, Marcotrigiano J, Gorbalenya A E, Rice C M. The NS5A protein of hepatitis C virus is a zinc metalloprotein. J Biol Chem. 2004; 279(47) 48576-48587
- 96 Brass V, Bieck E, Montserret R et al.. An amino-terminal amphipathic alpha-helix mediates membrane association of the hepatitis C virus nonstructural protein 5A. J Biol Chem. 2002; 277(10) 8130-8139
- 97 Penin F, Brass V, Appel N et al.. Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A. J Biol Chem. 2004; 279(39) 40835-40843
- 98 Hinson E R, Cresswell P. The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic alpha-helix. Proc Natl Acad Sci U S A. 2009; 106(48) 20452-20457
- 99 Tellinghuisen T L, Marcotrigiano J, Rice C M. Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase. Nature. 2005; 435(7040) 374-379
- 100 Tellinghuisen T L, Foss K L, Treadaway J C, Rice C M. Identification of residues required for RNA replication in domains II and III of the hepatitis C virus NS5A protein. J Virol. 2008; 82(3) 1073-1083
- 101 Appel N, Zayas M, Miller S et al.. Essential role of domain III of nonstructural protein 5A for hepatitis C virus infectious particle assembly. PLoS Pathog. 2008; 4(3) e1000035
- 102 Behrens S E, Tomei L, De Francesco R. Identification and properties of the RNA-dependent RNA polymerase of hepatitis C virus. EMBO J. 1996; 15(1) 12-22
- 103 Lohmann V, Körner F, Herian U, Bartenschlager R. Biochemical properties of hepatitis C virus NS5B RNA-dependent RNA polymerase and identification of amino acid sequence motifs essential for enzymatic activity. J Virol. 1997; 71(11) 8416-8428
- 104 Zhong W, Uss A S, Ferrari E, Lau J Y, Hong Z. De novo initiation of RNA synthesis by hepatitis C virus nonstructural protein 5B polymerase. J Virol. 2000; 74(4) 2017-2022
- 105 Lesburg C A, Cable M B, Ferrari E, Hong Z, Mannarino A F, Weber P C. Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site. Nat Struct Biol. 1999; 6(10) 937-943
- 106 Lohmann V, Overton H, Bartenschlager R. Selective stimulation of hepatitis C virus and pestivirus NS5B RNA polymerase activity by GTP. J Biol Chem. 1999; 274(16) 10807-10815
- 107 Bressanelli S, Tomei L, Rey F A, De Francesco R. Structural analysis of the hepatitis C virus RNA polymerase in complex with ribonucleotides. J Virol. 2002; 76(7) 3482-3492
- 108 André P, Komurian-Pradel F, Deforges S et al.. Characterization of low- and very-low-density hepatitis C virus RNA-containing particles. J Virol. 2002; 76(14) 6919-6928
- 109 André P, Perlemuter G, Budkowska A, Bréchot C, Lotteau V. Hepatitis C virus particles and lipoprotein metabolism. Semin Liver Dis. 2005; 25(1) 93-104
- 110 Chang 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(24) 13783-13793
- 111 Meunier 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(19) 9647-9656
- 112 Parent R, Qu X, Petit M A, Beretta L. The heat shock cognate protein 70 is associated with hepatitis C virus particles and modulates virus infectivity. Hepatology. 2009; 49(6) 1798-1809
- 113 Koutsoudakis G, Kaul A, Steinmann E et al.. Characterization of the early steps of hepatitis C virus infection by using luciferase reporter viruses. J Virol. 2006; 80(11) 5308-5320
- 114 Barth H, Schafer C, Adah M I et al.. Cellular binding of hepatitis C virus envelope glycoprotein E2 requires cell surface heparan sulfate. J Biol Chem. 2003; 278(42) 41003-41012
- 115 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(22) 12766-12771
- 116 Molina S, Castet V, Fournier-Wirth C et al.. The low-density lipoprotein receptor plays a role in the infection of primary human hepatocytes by hepatitis C virus. J Hepatol. 2007; 46(3) 411-419
- 117 Wünschmann S, Medh J D, Klinzmann D, Schmidt W N, Stapleton J T. Characterization of hepatitis C virus (HCV) and HCV E2 interactions with CD81 and the low-density lipoprotein receptor. J Virol. 2000; 74(21) 10055-10062
- 118 Coyne C B, Bergelson J M. Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions. Cell. 2006; 124(1) 119-131
- 119 Scarselli E, Ansuini H, Cerino R et al.. The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J. 2002; 21(19) 5017-5025
- 120 Pileri P, Uematsu Y, Campagnoli S et al.. Binding of hepatitis C virus to CD81. Science. 1998; 282(5390) 938-941
- 121 Evans M J, von Hahn T, Tscherne D M et al.. Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature. 2007; 446(7137) 801-805
- 122 Liu S, Yang W, Shen L, Turner J R, Coyne C B, Wang T. Tight junction proteins claudin-1 and occludin control hepatitis C virus entry and are downregulated during infection to prevent superinfection. J Virol. 2009; 83(4) 2011-2014
- 123 Blanchard E, Belouzard S, Goueslain L et al.. Hepatitis C virus entry depends on clathrin-mediated endocytosis. J Virol. 2006; 80(14) 6964-6972
- 124 Tscherne D M, Jones C T, Evans M J, Lindenbach B D, McKeating J A, Rice C M. Time- and temperature-dependent activation of hepatitis C virus for low-pH-triggered entry. J Virol. 2006; 80(4) 1734-1741
- 125 Modis Y, Ogata S, Clements D, Harrison S C. Structure of the dengue virus envelope protein after membrane fusion. Nature. 2004; 427(6972) 313-319
- 126 Singh I, Helenius A. Role of ribosomes in Semliki Forest virus nucleocapsid uncoating. J Virol. 1992; 66(12) 7049-7058
- 127 Wengler G, Wengler G. Identification of a transfer of viral core protein to cellular ribosomes during the early stages of alphavirus infection. Virology. 1984; 134(2) 435-442
- 128 Gosert R, Egger D, Lohmann V et al.. Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons. J Virol. 2003; 77(9) 5487-5492
- 129 Mackenzie J. Wrapping things up about virus RNA replication. Traffic. 2005; 6(11) 967-977
- 130 Welsch S, Miller S, Romero-Brey I et al.. Composition and three-dimensional architecture of the dengue virus replication and assembly sites. Cell Host Microbe. 2009; 5(4) 365-375
- 131 Quinkert D, Bartenschlager R, Lohmann V. Quantitative analysis of the hepatitis C virus replication complex. J Virol. 2005; 79(21) 13594-13605
- 132 Schlegel A, Giddings Jr T H, Ladinsky M S, Kirkegaard K. Cellular origin and ultrastructure of membranes induced during poliovirus infection. J Virol. 1996; 70(10) 6576-6588
- 133 Taylor M P, Kirkegaard K. Potential subversion of autophagosomal pathway by picornaviruses. Autophagy. 2008; 4(3) 286-289
- 134 Tai A W, Benita Y, Peng L F et al.. A functional genomic screen identifies cellular cofactors of hepatitis C virus replication. Cell Host Microbe. 2009; 5(3) 298-307
- 135 Berger K L, Cooper J D, Heaton N S et al.. Roles for endocytic trafficking and phosphatidylinositol 4-kinase III alpha in hepatitis C virus replication. Proc Natl Acad Sci U S A. 2009; 106(18) 7577-7582
- 136 Li Q, Brass A L, Ng A et al.. A genome-wide genetic screen for host factors required for hepatitis C virus propagation. Proc Natl Acad Sci U S A. 2009; 106(38) 16410-16415
- 137 Trotard M, Lepère-Douard C, Régeard M et al.. Kinases required in hepatitis C virus entry and replication highlighted by small interference RNA screening. FASEB J. 2009; 23(11) 3780-3789
- 138 Borawski J, Troke P, Puyang X et al.. Class III phosphatidylinositol 4-kinase alpha and beta are novel host factor regulators of hepatitis C virus replication. J Virol. 2009; 83(19) 10058-10074
- 139 Vaillancourt F H, Pilote L, Cartier M et al.. Identification of a lipid kinase as a host factor involved in hepatitis C virus RNA replication. Virology. 2009; 387(1) 5-10
- 140 Hsu N Y, Ilnytska O, Belov G et al.. Viral reorganization of the secretory pathway generates distinct organelles for RNA replication. Cell. 2010; 141(5) 799-811
- 141 Wang C, Gale Jr M, Keller B C et al.. Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. Mol Cell. 2005; 18(4) 425-434
- 142 Ye J, Wang C, Sumpter Jr R, Brown M S, Goldstein J L, Gale Jr M. Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Natl Acad Sci U S A. 2003; 100(26) 15865-15870
- 143 Kapadia S B, Chisari F V. Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proc Natl Acad Sci U S A. 2005; 102(7) 2561-2566
- 144 Yang W, Hood B L, Chadwick S L et al.. Fatty acid synthase is up-regulated during hepatitis C virus infection and regulates hepatitis C virus entry and production. Hepatology. 2008; 48(5) 1396-1403
- 145 Sakamoto H, Okamoto K, Aoki M et al.. Host sphingolipid biosynthesis as a target for hepatitis C virus therapy. Nat Chem Biol. 2005; 1(6) 333-337
- 146 Gastaminza P, Cheng G, Wieland S, Zhong J, Liao W, Chisari F V. Cellular determinants of hepatitis C virus assembly, maturation, degradation, and secretion. J Virol. 2008; 82(5) 2120-2129
- 147 Huang H, Sun F, Owen D M et al.. Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins. Proc Natl Acad Sci U S A. 2007; 104(14) 5848-5853
- 148 Jiang J, Luo G. Apolipoprotein E but not B is required for the formation of infectious hepatitis C virus particles. J Virol. 2009; 83(24) 12680-12691
- 149 Benga W J, Krieger S E, Dimitrova M et al.. Apolipoprotein E interacts with hepatitis C virus nonstructural protein 5A and determines assembly of infectious particles. Hepatology. 2010; 51(1) 43-53
- 150 Aizaki H, Morikawa K, Fukasawa M et al.. Critical role of virion-associated cholesterol and sphingolipid in hepatitis C virus infection. J Virol. 2008; 82(12) 5715-5724
- 151 Thomas D L, Thio C L, Martin M P et al.. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature. 2009; 461(7265) 798-801
- 152 International HapMap Consortium . A haplotype map of the human genome. Nature. 2005; 437(7063) 1299-1320
- 153 Marcello T, Grakoui A, Barba-Spaeth G et al.. Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Gastroenterology. 2006; 131(6) 1887-1898
- 154 Sarasin-Filipowicz M, Oakeley E J, Duong F H et al.. Interferon signaling and treatment outcome in chronic hepatitis C. Proc Natl Acad Sci U S A. 2008; 105(19) 7034-7039
- 155 Sarasin-Filipowicz M, Krol J, Markiewicz I, Heim M H, Filipowicz W. Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy. Nat Med. 2009; 15(1) 31-33
- 156 Vanwolleghem T, Bukh J, Meuleman P et al.. Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human liver-chimeric mice from infection with a homologous hepatitis C virus strain. Hepatology. 2008; 47(6) 1846-1855
- 157 Eren R, Landstein D, Terkieltaub D et al.. Preclinical evaluation of two neutralizing human monoclonal antibodies against hepatitis C virus (HCV): a potential treatment to prevent HCV reinfection in liver transplant patients. J Virol. 2006; 80(6) 2654-2664
- 158 Meuleman P, Hesselgesser J, Paulson M et al.. Anti-CD81 antibodies can prevent a hepatitis C virus infection in vivo. Hepatology. 2008; 48(6) 1761-1768
- 159 Grakoui A, Wychowski C, Lin C, Feinstone S M, Rice C M. Expression and identification of hepatitis C virus polyprotein cleavage products. J Virol. 1993; 67(3) 1385-1395
- 160 Love R A, Parge H E, Wickersham J A et al.. The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site. Cell. 1996; 87(2) 331-342
- 161 Kim J L, Morgenstern K A, Lin C et al.. Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. Cell. 1996; 87(2) 343-355
- 162 Landro J A, Raybuck S A, Luong Y P et al.. Mechanistic role of an NS4A peptide cofactor with the truncated NS3 protease of hepatitis C virus: elucidation of the NS4A stimulatory effect via kinetic analysis and inhibitor mapping. Biochemistry. 1997; 36(31) 9340-9348
- 163 Steinkühler C, Biasiol G, Brunetti M et al.. Product inhibition of the hepatitis C virus NS3 protease. Biochemistry. 1998; 37(25) 8899-8905
- 164 Sarrazin C, Zeuzem S. Resistance to direct antiviral agents in patients with hepatitis C virus infection. Gastroenterology. 2010; 138(2) 447-462
- 165 Walker M P, Hong Z. HCV RNA-dependent RNA polymerase as a target for antiviral development. Curr Opin Pharmacol. 2002; 2(5) 534-540
- 166 De Francesco R, Tomei L, Altamura S, Summa V, Migliaccio G. Approaching a new era for hepatitis C virus therapy: inhibitors of the NS3-4A serine protease and the NS5B RNA-dependent RNA polymerase. Antiviral Res. 2003; 58(1) 1-16
- 167 De Francesco R, Rice C M. New therapies on the horizon for hepatitis C: are we close?. Clin Liver Dis. 2003; 7(1) 211-242, xi xi
- 168 Tomei L, Altamura S, Bartholomew L et al.. Mechanism of action and antiviral activity of benzimidazole-based allosteric inhibitors of the hepatitis C virus RNA-dependent RNA polymerase. J Virol. 2003; 77(24) 13225-13231
- 169 Gu B, Johnston V K, Gutshall L L et al.. Arresting initiation of hepatitis C virus RNA synthesis using heterocyclic derivatives. J Biol Chem. 2003; 278(19) 16602-16607
- 170 Dhanak D, Duffy K J, Johnston V K et al.. Identification and biological characterization of heterocyclic inhibitors of the hepatitis C virus RNA-dependent RNA polymerase. J Biol Chem. 2002; 277(41) 38322-38327
- 171 Chen C M, He Y, Lu L et al.. Activity of a potent hepatitis C virus polymerase inhibitor in the chimpanzee model. Antimicrob Agents Chemother. 2007; 51(12) 4290-4296
- 172 Brown N A. Progress towards improving antiviral therapy for hepatitis C with hepatitis C virus polymerase inhibitors. Part I: Nucleoside analogues. Expert Opin Investig Drugs. 2009; 18(6) 709-725
- 173 Gao M, Nettles R E, Belema M et al.. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature. 2010; 465(7294) 96-100
- 174 Lemm J A, O'Boyle II D, Liu M et al.. Identification of hepatitis C virus NS5A inhibitors. J Virol. 2010; 84(1) 482-491
- 175 Tomei L, Altamura S, Bartholomew L et al.. Characterization of the inhibition of hepatitis C virus RNA replication by nonnucleosides. J Virol. 2004; 78(2) 938-946
- 176 Mo H, Lu L, Pilot-Matias T et al.. Mutations conferring resistance to a hepatitis C virus (HCV) RNA-dependent RNA polymerase inhibitor alone or in combination with an HCV serine protease inhibitor in vitro. Antimicrob Agents Chemother. 2005; 49(10) 4305-4314
- 177 Koev G, Dekhtyar T, Han L et al.. Antiviral interactions of an HCV polymerase inhibitor with an HCV protease inhibitor or interferon in vitro. Antiviral Res. 2007; 73(1) 78-83
- 178 Gane E J, Roberts S K, Stedman C et al.. First-in-man demonstration of potent antiviral activity with a nucleoside polymerase
(R7128) and protease (R7227/ITMN-191) inhibitor combination in HCV: safety, pharmacokinetics,
and virologic results from INFORM-1. Abstract 1046 presented at the European Association for the Study of the Liver April 22–26, 2009 Copenhagen, Denmark;
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- 179 Kaul A, Stauffer S, Berger C et al.. Essential role of cyclophilin A for hepatitis C virus replication and virus production and possible link to polyprotein cleavage kinetics. PLoS Pathog. 2009; 5(8) e1000546
- 180 Yang F, Robotham J M, Nelson H B, Irsigler A, Kenworthy R, Tang H. Cyclophilin A is an essential cofactor for hepatitis C virus infection and the principal mediator of cyclosporine resistance in vitro. J Virol. 2008; 82(11) 5269-5278
- 181 Chatterji U, Bobardt M, Selvarajah S et al.. The isomerase active site of cyclophilin A is critical for hepatitis C virus replication. J Biol Chem. 2009; 284(25) 16998-17005
- 182 Ciesek S, Steinmann E, Wedemeyer H et al.. Cyclosporine A inhibits hepatitis C virus nonstructural protein 2 through cyclophilin A. Hepatology. 2009; 50(5) 1638-1645
- 183 Hanoulle X, Badillo A, Wieruszeski J M et al.. Hepatitis C virus NS5A protein is a substrate for the peptidyl-prolyl cis/trans isomerase activity of cyclophilins A and B. J Biol Chem. 2009; 284(20) 13589-13601
- 184 Ma S, Boerner J E, TiongYip C et al.. NIM811, a cyclophilin inhibitor, exhibits potent in vitro activity against hepatitis C virus alone or in combination with alpha interferon. Antimicrob Agents Chemother. 2006; 50(9) 2976-2982
- 185 Paeshuyse J, Kaul A, De Clercq E et al.. The non-immunosuppressive cyclosporin DEBIO-025 is a potent inhibitor of hepatitis C virus replication in vitro. Hepatology. 2006; 43(4) 761-770
- 186 Flisiak R, Horban A, Gallay P et al.. The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus. Hepatology. 2008; 47(3) 817-826
- 187 del Real G, Jiménez-Baranda S, Mira E et al.. Statins inhibit HIV-1 infection by down-regulating Rho activity. J Exp Med. 2004; 200(4) 541-547
- 188 Giguère J F, Tremblay M J. Statin compounds reduce human immunodeficiency virus type 1 replication by preventing the interaction between virion-associated host intercellular adhesion molecule 1 and its natural cell surface ligand LFA-1. J Virol. 2004; 78(21) 12062-12065
- 189 Liu S, Rodriguez A V, Tosteson M T. Role of simvastatin and methyl-beta-cyclodextrin [corrected] on inhibition of poliovirus infection. Biochem Biophys Res Commun. 2006; 347(1) 51-59
- 190 Ikeda M, Abe K, Yamada M, Dansako H, Naka K, Kato N. Different anti-HCV profiles of statins and their potential for combination therapy with interferon. Hepatology. 2006; 44(1) 117-125
- 191 Amemiya F, Maekawa S, Itakura Y et al.. Targeting lipid metabolism in the treatment of hepatitis C virus infection. J Infect Dis. 2008; 197(3) 361-370
- 192 Delang L, Paeshuyse J, Vliegen I et al.. Statins potentiate the in vitro anti-hepatitis C virus activity of selective hepatitis C virus inhibitors and delay or prevent resistance development. Hepatology. 2009; 50(1) 6-16
- 193 Ambros V. The functions of animal microRNAs. Nature. 2004; 431(7006) 350-355
- 194 Bartel D P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2) 281-297
- 195 Grimson A, Farh K K, Johnston W K, Garrett-Engele P, Lim L P, Bartel D P. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell. 2007; 27(1) 91-105
- 196 Kloosterman W P, Plasterk R H. The diverse functions of microRNAs in animal development and disease. Dev Cell. 2006; 11(4) 441-450
- 197 Randall G, Panis M, Cooper J D et al.. Cellular cofactors affecting hepatitis C virus infection and replication. Proc Natl Acad Sci U S A. 2007; 104(31) 12884-12889
- 198 Niepmann M. Activation of hepatitis C virus translation by a liver-specific microRNA. Cell Cycle. 2009; 8(10) 1473-1477
- 199 Elmén J, Lindow M, Schütz S et al.. LNA-mediated microRNA silencing in non-human primates. Nature. 2008; 452(7189) 896-899
- 200 Wakita T, Pietschmann T, Kato T et al.. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med. 2005; 11(7) 791-796
- 201 Lindenbach B D, Evans M J, Syder A J et al.. Complete replication of hepatitis C virus in cell culture. Science. 2005; 309(5734) 623-626
- 202 Zhong J, Gastaminza P, Cheng G et al.. Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci U S A. 2005; 102(26) 9294-9299
- 203 Masaki T, Suzuki R, Murakami K et al.. Interaction of hepatitis C virus nonstructural protein 5A with core protein is critical for the production of infectious virus particles. J Virol. 2008; 82(16) 7964-7976
Ralf BartenschlagerPh.D.
Department of Infectious Diseases, Molecular Virology
Heidelberg University, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany
eMail: Ralf_Bartenschlager@med.uni-heidelberg.de