Replication of hepatitis C virus

Exciting progress has recently been made in understanding the replication of hepatitis C virus, a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. The development of complete cell-culture systems should now enable the systematic dissection of the entire viral lifecycle, providing insights into the hitherto difficult-to-study early and late steps. These efforts have already translated into the identification of novel antiviral targets and the development of new therapeutic strategies, some of which are currently undergoing clinical evaluation.

[1]  F. Penin,et al.  Interaction of hepatitis C virus proteins with host cell membranes and lipids. , 2002, Trends in cell biology.

[2]  D. Harats,et al.  The low-density lipoprotein receptor plays a role in the infection of primary human hepatocytes by hepatitis C virus. , 2007, Journal of hepatology.

[3]  Stanley M Lemon,et al.  Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[4]  B. Becker,et al.  Non-structural protein 3 of hepatitis C virus inhibits phosphorylation mediated by cAMP-dependent protein kinase. , 1996, European journal of biochemistry.

[5]  H. Parge,et al.  The Crystal Structure of Hepatitis C Virus NS3 Proteinase Reveals a Trypsin-like Fold and a Structural Zinc Binding Site , 1996, Cell.

[6]  R. De Francesco,et al.  The Hepatitis C Virus NS3 Proteinase: Structure and Function of a Zinc-Containing Serine Proteinase , 1998, Antiviral therapy.

[7]  Darius Moradpour,et al.  Structural biology of hepatitis C virus , 2004, Hepatology.

[8]  J. Bukh A critical role for the chimpanzee model in the study of hepatitis C , 2004, Hepatology.

[9]  R. Hamatake,et al.  De Novo Initiation of RNA Synthesis by the RNA-Dependent RNA Polymerase (NS5B) of Hepatitis C Virus , 2000, Journal of Virology.

[10]  Charles M. Rice,et al.  Flaviviridae :T he Viruses and Their Replication , 2007 .

[11]  M. Yanagi,et al.  In vivo analysis of the 3' untranslated region of the hepatitis C virus after in vitro mutagenesis of an infectious cDNA clone. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Christopher T. Jones,et al.  Hepatitis C Virus p7 and NS2 Proteins Are Essential for Production of Infectious Virus , 2007, Journal of Virology.

[13]  R. De Francesco,et al.  The α Isoform of Protein Kinase CKI Is Responsible for Hepatitis C Virus NS5A Hyperphosphorylation , 2006, Journal of Virology.

[14]  M. Yanagi,et al.  Toward a surrogate model for hepatitis C virus: An infectious molecular clone of the GB virus-B hepatitis agent. , 1999, Virology.

[15]  C. Rice,et al.  Hepatitis C Virus-Encoded Enzymatic Activities and Conserved RNA Elements in the 3′ Nontranslated Region Are Essential for Virus Replication In Vivo , 2000, Journal of Virology.

[16]  T. Tsuji,et al.  Genetic organization and diversity of the 3' noncoding region of the hepatitis C virus genome. , 1996, Virology.

[17]  Ralf Bartenschlager,et al.  Viral and Cellular Determinants of Hepatitis C Virus RNA Replication in Cell Culture , 2003, Journal of Virology.

[18]  C. Rogler,et al.  Liver repopulation with xenogenic hepatocytes in B and T cell-deficient mice leads to chronic hepadnavirus infection and clonal growth of hepatocellular carcinoma. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Mackenzie Wrapping Things up about Virus RNA Replication , 2005, Traffic.

[20]  J. Rakela,et al.  Hepatitis C virus negative strand RNA is not detected in peripheral blood mononuclear cells and viral sequences are identical to those in serum: a case against extrahepatic replication. , 1997, The Journal of general virology.

[21]  Ralf Bartenschlager,et al.  Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus , 2005, Nature.

[22]  R. Francesco,et al.  Challenges and successes in developing new therapies for hepatitis C , 2005, Nature.

[23]  J. Tratschin,et al.  Nucleotide sequence of classical swine fever virus strain Alfort/187 and transcription of infectious RNA from stably cloned full-length cDNA , 1996, Journal of virology.

[24]  Charles M. Rice,et al.  Unravelling hepatitis C virus replication from genome to function , 2005, Nature.

[25]  I. Tinoco,et al.  RNA translocation and unwinding mechanism of HCV NS3 helicase and its coordination by ATP , 2006, Nature.

[26]  L. Theilmann,et al.  Peripheral blood leukocytes serve as a possible extrahepatic site for hepatitis C virus replication. , 1993, The Journal of general virology.

[27]  C. Rice,et al.  Formation of native hepatitis C virus glycoprotein complexes , 1997, Journal of virology.

[28]  G. Migliaccio,et al.  Biosynthesis and biochemical properties of the hepatitis C virus core protein , 1994, Journal of virology.

[29]  C. Rice,et al.  Phosphorylation of hepatitis C virus nonstructural protein 5A modulates its protein interactions and viral RNA replication. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[30]  C. Rice,et al.  Subcellular Localization, Stability, andtrans-Cleavage Competence of the Hepatitis C Virus NS3-NS4A Complex Expressed in Tetracycline-Regulated Cell Lines , 2000, Journal of Virology.

[31]  R. Bartenschlager,et al.  The NS3/4A proteinase of the hepatitis C virus: unravelling structure and function of an unusual enzyme and a prime target for antiviral therapy , 1999, Journal of viral hepatitis.

[32]  C. Hagedorn,et al.  Expression of recombinant hepatitis C virus non-structural protein 5B in Escherichia coli. , 1998, Virus research.

[33]  E. Wimmer,et al.  Poliovirus/Hepatitis C Virus (Internal Ribosomal Entry Site-Core) Chimeric Viruses: Improved Growth Properties through Modification of a Proteolytic Cleavage Site and Requirement for Core RNA Sequences but Not for Core-Related Polypeptides , 1999, Journal of Virology.

[34]  P. C. Haasnoot,et al.  The influence of AUG codons in the hepatitis C virus 5' nontranslated region on translation and mapping of the translation initiation window. , 1996, Virology.

[35]  M. Lai,et al.  Hepatitis C virus core protein interacts with the cytoplasmic tail of lymphotoxin-beta receptor , 1997, Journal of virology.

[36]  C. Rice,et al.  A central region in the hepatitis C virus NS4A protein allows formation of an active NS3-NS4A serine proteinase complex in vivo and in vitro , 1995, Journal of virology.

[37]  Charles M. Rice,et al.  Architects of assembly: roles of Flaviviridae non-structural proteins in virion morphogenesis , 2008, Nature Reviews Microbiology.

[38]  J. G. Patton,et al.  Direct evidence that polypyrimidine tract binding protein (PTB) is essential for internal initiation of translation of encephalomyocarditis virus RNA. , 1995, RNA.

[39]  E. De Clercq,et al.  The non‐immunosuppressive cyclosporin DEBIO‐025 is a potent inhibitor of hepatitis C virus replication in vitro , 2006, Hepatology.

[40]  K. Shimotohno,et al.  Hepatitis C virus-encoded nonstructural protein NS4A has versatile functions in viral protein processing , 1995, Journal of virology.

[41]  F. Penin,et al.  Membrane Association of the RNA-Dependent RNA Polymerase Is Essential for Hepatitis C Virus RNA Replication , 2004, Journal of Virology.

[42]  J. Dubuisson,et al.  Hepatitis C Virus Glycoprotein Complex Localization in the Endoplasmic Reticulum Involves a Determinant for Retention and Not Retrieval* , 1998, The Journal of Biological Chemistry.

[43]  E. Holmes,et al.  Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. , 1993, The Journal of general virology.

[44]  M. Gale,et al.  Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins , 2007, Proceedings of the National Academy of Sciences.

[45]  G. Alexander,et al.  Human hepatic glyceraldehyde-3-phosphate dehydrogenase binds to the poly(U) tract of the 3' non-coding region of hepatitis C virus genomic RNA. , 1999, The Journal of general virology.

[46]  Ralf Bartenschlager,et al.  Quantitative Analysis of the Hepatitis C Virus Replication Complex , 2005, Journal of Virology.

[47]  S. Evans,et al.  The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine , 2003, FEBS letters.

[48]  Joseph D Puglisi,et al.  Structure of HCV IRES domain II determined by NMR , 2003, Nature Structural Biology.

[49]  F. Chisari,et al.  Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[50]  Zhijian J. Chen,et al.  Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-κB and IRF3 , 2005, Cell.

[51]  R. Jackson,et al.  Unique features of internal initiation of hepatitis C virus RNA translation. , 1995, The EMBO journal.

[52]  R. Francesco,et al.  Identification and properties of the RNA‐dependent RNA polymerase of hepatitis C virus. , 1996, The EMBO journal.

[53]  R. Bartenschlager,et al.  In vitro studies on the activation of the hepatitis C virus NS3 proteinase by the NS4A cofactor. , 1996, Virology.

[54]  Y. Matsuura,et al.  Hepatitis C virus RNA replication is regulated by FKBP8 and Hsp90 , 2006, The EMBO journal.

[55]  J. Silver,et al.  Replication of Subgenomic Hepatitis C Virus Rnas in a Hepatoma Cell Line , 1999 .

[56]  R. Jackson,et al.  Internal initiation of translation of hepatitis C virus RNA: the ribosome entry site is at the authentic initiation codon. , 1996, RNA.

[57]  B. Bartosch,et al.  Cell entry of hepatitis C virus. , 2006, Virology.

[58]  Wei Zhang,et al.  Structure of Dengue Virus Implications for Flavivirus Organization, Maturation, and Fusion , 2002, Cell.

[59]  J. Bukh,et al.  Development and characterization of hepatitis C virus genotype 1‐7 cell culture systems: Role of CD81 and scavenger receptor class B type I and effect of antiviral drugs , 2009, Hepatology.

[60]  R. De Francesco,et al.  In Vitro Activity of Hepatitis C Virus Protease NS3 Purified from Recombinant Baculovirus-infected Sf9 Cells (*) , 1996, The Journal of Biological Chemistry.

[61]  M. Houghton,et al.  Binding of hepatitis C virus to CD81. , 1998, Science.

[62]  J. Choe,et al.  Characterization of RNA binding activity and RNA helicase activity of the hepatitis C virus NS3 protein. , 1996, Biochemical and biophysical research communications.

[63]  T. Roskams,et al.  Morphological and biochemical characterization of a human liver in a uPA‐SCID mouse chimera , 2005, Hepatology.

[64]  C. Rice,et al.  Identification of a highly conserved sequence element at the 3' terminus of hepatitis C virus genome RNA , 1996, Journal of virology.

[65]  Se-Hwan Yang,et al.  Hepatitis C Virus Core from Two Different Genotypes Has an Oncogenic Potential but Is Not Sufficient for Transforming Primary Rat Embryo Fibroblasts in Cooperation with the H-ras Oncogene , 1998, Journal of Virology.

[66]  F. Penin,et al.  Subcellular Localization and Topology of the p7 Polypeptide of Hepatitis C Virus , 2002, Journal of Virology.

[67]  M. Houghton,et al.  5' end-dependent translation initiation of hepatitis C viral RNA and the presence of putative positive and negative translational control elements within the 5' untranslated region. , 1992, Virology.

[68]  B. Bartosch,et al.  Infectious Hepatitis C Virus Pseudo-particles Containing Functional E1–E2 Envelope Protein Complexes , 2003, The Journal of experimental medicine.

[69]  G. Deléage,et al.  Conservation of the Conformation and Positive Charges of Hepatitis C Virus E2 Envelope Glycoprotein Hypervariable Region 1 Points to a Role in Cell Attachment , 2001, Journal of Virology.

[70]  A. Kwong,et al.  Viral and cellular RNA helicases as antiviral targets , 2005, Nature Reviews Drug Discovery.

[71]  Ralf Bartenschlager,et al.  Kissing-Loop Interaction in the 3′ End of the Hepatitis C Virus Genome Essential for RNA Replication , 2005, Journal of Virology.

[72]  H. Parge,et al.  The conformation of hepatitis C virus NS3 proteinase with and without NS4A: a structural basis for the activation of the enzyme by its cofactor. , 1998, Clinical and diagnostic virology.

[73]  C. Bréchot,et al.  Infection of peripheral mononuclear blood cells by hepatitis C virus. , 1992, Journal of hepatology.

[74]  K. Meyer,et al.  Functional Role of Hepatitis C Virus Chimeric Glycoproteins in the Infectivity of Pseudotyped Virus , 1998, Journal of Virology.

[75]  S. Iacovacci,et al.  Detection of a 5' UTR variation in the HCV genome after a long-term in vitro infection. , 1995, Research in virology.

[76]  F. Chisari,et al.  Lack of detection of negative-strand hepatitis C virus RNA in peripheral blood mononuclear cells and other extrahepatic tissues by the highly strand-specific rTth reverse transcriptase PCR , 1995, Journal of virology.

[77]  M. Vidal,et al.  Hepatitis C virus infection protein network , 2008, Molecular systems biology.

[78]  C. Rice,et al.  Insertion of Green Fluorescent Protein into Nonstructural Protein 5A Allows Direct Visualization of Functional Hepatitis C Virus Replication Complexes , 2004, Journal of Virology.

[79]  C. Rice,et al.  Characterization of the hepatitis C virus-encoded serine proteinase: determination of proteinase-dependent polyprotein cleavage sites , 1993, Journal of virology.

[80]  M. Stempniak,et al.  The NS3 proteinase domain of hepatitis C virus is a zinc-containing enzyme , 1997, Journal of virology.

[81]  C. Sureau,et al.  In vitro infection of adult normal human hepatocytes in primary culture by hepatitis C virus. , 1998, The Journal of general virology.

[82]  M. St. Claire,et al.  Mutations that permit efficient replication of hepatitis C virus RNA in Huh-7 cells prevent productive replication in chimpanzees , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[83]  Ying Li,et al.  Complex of NS3 protease and NS4A peptide of BK strain hepatitis C virus: A 2.2 Å resolution structure in a hexagonal crystal form , 1998, Protein science : a publication of the Protein Society.

[84]  J. Dubuisson,et al.  The Transmembrane Domain of Hepatitis C Virus Glycoprotein E1 Is a Signal for Static Retention in the Endoplasmic Reticulum , 1999, Journal of Virology.

[85]  R. Bartenschlager,et al.  Production of infectious hepatitis C virus in tissue culture from a cloned viral genome , 2005, Nature Medicine.

[86]  P. Weber,et al.  Molecular views of viral polyprotein processing revealed by the crystal structure of the hepatitis C virus bifunctional protease-helicase. , 1999, Structure.

[87]  C. Rice,et al.  Formation and intracellular localization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia and Sindbis viruses , 1994, Journal of virology.

[88]  F. Penin,et al.  Function follows form: the structure of the N-terminal domain of HCV NS5A. , 2005, Hepatology.

[89]  M. Shapiro,et al.  Infection of a chimpanzee with hepatitis C virus grown in cell culture. , 1998, The Journal of general virology.

[90]  K. Shimotohno,et al.  Hepatitis C virus polyprotein processing: kinetics and mutagenic analysis of serine proteinase-dependent cleavage , 1994, Journal of virology.

[91]  A. Shavinskaya,et al.  The Lipid Droplet Binding Domain of Hepatitis C Virus Core Protein Is a Major Determinant for Efficient Virus Assembly* , 2007, Journal of Biological Chemistry.

[92]  R. Bartenschlager,et al.  Genetic Analysis of Sequences in the 3′ Nontranslated Region of Hepatitis C Virus That Are Important for RNA Replication , 2002, Journal of Virology.

[93]  Shin C. Chang,et al.  Specific Interaction between the Hepatitis C Virus NS5B RNA Polymerase and the 3′ End of the Viral RNA , 1999, Journal of Virology.

[94]  F. Penin,et al.  The hepatitis C virus Core protein is a potent nucleic acid chaperone that directs dimerization of the viral (+) strand RNA in vitro. , 2004, Nucleic acids research.

[95]  H. Langen,et al.  Hepatitis C virus core protein: carboxy-terminal boundaries of two processed species suggest cleavage by a signal peptide peptidase. , 1996, Virology.

[96]  R. Purcell,et al.  Hepatitis C virus: Detection of intracellular virus particles by electron microscop , 1996 .

[97]  A. Kirn,et al.  In vitro infection of peripheral blood mononuclear cells by hepatitis C virus. , 1995, The Journal of general virology.

[98]  N Enomoto,et al.  Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. , 1996, The New England journal of medicine.

[99]  J. Mukaigawa,et al.  Cultivation of hepatitis C virus in primary hepatocyte culture from patients with chronic hepatitis C results in release of high titre infectious virus. , 1996, The Journal of general virology.

[100]  S. You,et al.  A cis-Acting Replication Element in the Sequence Encoding the NS5B RNA-Dependent RNA Polymerase Is Required for Hepatitis C Virus RNA Replication , 2004, Journal of Virology.

[101]  A. Kwong,et al.  Structure of the hepatitis C virus RNA helicase domain , 1997, Nature Structural Biology.

[102]  P. André,et al.  Hepatitis C virus particles and lipoprotein metabolism. , 2005, Seminars in liver disease.

[103]  S. Quake,et al.  Discovery of a hepatitis C target and its pharmacological inhibitors by microfluidic affinity analysis , 2008, Nature Biotechnology.

[104]  J. Jiricny,et al.  RNA-dependent RNA polymerase of hepatitis C virus. , 1996, Methods in enzymology.

[105]  A. Weiner,et al.  Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution , 1992, Journal of virology.

[106]  K. Zhou,et al.  Crystal structure of an RNA tertiary domain essential to HCV IRES-mediated translation initiation , 2002, Nature Structural Biology.

[107]  S. Dash,et al.  Transfection of HepG2 cells with infectious hepatitis C virus genome. , 1997, The American journal of pathology.

[108]  C. Rice,et al.  Molecular characterization of hepatitis C virus. , 1998, Current studies in hematology and blood transfusion.

[109]  Y. Masuho,et al.  Identification of the sequence on NS4A required for enhanced cleavage of the NS5A/5B site by hepatitis C virus NS3 protease , 1996, Journal of virology.

[110]  C. Rice,et al.  Infectious Bovine Viral Diarrhea Virus (Strain NADL) RNA from Stable cDNA Clones: a Cellular Insert Determines NS3 Production and Viral Cytopathogenicity , 1998, Journal of Virology.

[111]  S. Lemon,et al.  Almost the entire 5′ non‐translated region of hepatitis C virus is required for cap‐independent translation , 1995, FEBS letters.

[112]  R. Bartenschlager,et al.  Identification of the Hepatitis C Virus RNA Replication Complex in Huh-7 Cells Harboring Subgenomic Replicons , 2003, Journal of Virology.

[113]  K. Shimotohno,et al.  The N-terminal region of hepatitis C virus-encoded NS5A is important for NS4A-dependent phosphorylation , 1997, Journal of virology.

[114]  C. Cameron,et al.  NS3 Helicase from the Hepatitis C Virus Can Function as a Monomer or Oligomer Depending on Enzyme and Substrate Concentrations* , 2009, Journal of Biological Chemistry.

[115]  R. Francesco,et al.  Both NS3 and NS4A are required for proteolytic processing of hepatitis C virus nonstructural proteins , 1994, Journal of virology.

[116]  Ralf Bartenschlager,et al.  Modulation of Hepatitis C Virus NS5A Hyperphosphorylation by Nonstructural Proteins NS3, NS4A, and NS4B , 1999, Journal of Virology.

[117]  Claus W. Grassmann,et al.  Characterization of an Autonomous Subgenomic Pestivirus RNA Replicon , 1998, Journal of Virology.

[118]  Daniel Crisan,et al.  euHCVdb: the European hepatitis C virus database , 2006, Nucleic Acids Res..

[119]  C. Rice,et al.  Efficient initiation of HCV RNA replication in cell culture. , 2000, Science.

[120]  P. Weber,et al.  Mechanism of autoproteolysis at the NS2-NS3 junction of the hepatitis C virus polyprotein. , 1998, Trends in biochemical sciences.

[121]  N. Kato,et al.  Long-term human T-cell culture system supporting hepatitis C virus replication. , 1996, Biochemical and biophysical research communications.

[122]  F. Rey,et al.  Virus membrane-fusion proteins: more than one way to make a hairpin , 2006, Nature Reviews Microbiology.

[123]  W. Chi,et al.  The helicase activity associated with hepatitis C virus nonstructural protein 3 (NS3) , 1996, Journal of virology.

[124]  J. Doudna,et al.  Structural and mechanistic insights into hepatitis C viral translation initiation , 2007, Nature Reviews Microbiology.

[125]  R. Bartenschlager,et al.  Mutational Analysis of Hepatitis C Virus Nonstructural Protein 5A: Potential Role of Differential Phosphorylation in RNA Replication and Identification of a Genetically Flexible Domain , 2005, Journal of Virology.

[126]  R. Bartenschlager,et al.  Biochemical properties of hepatitis C virus NS5B RNA-dependent RNA polymerase and identification of amino acid sequence motifs essential for enzymatic activity , 1997, Journal of virology.

[127]  H. Hotta,et al.  Complex formation of NS5B with NS3 and NS4A proteins of hepatitis C virus. , 1998, Biochemical and biophysical research communications.

[128]  H. Yoshikura,et al.  Multicycle infection of hepatitis C virus in cell culture and inhibition by alpha and beta interferons , 1994, Journal of virology.

[129]  D. Stump,et al.  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. , 2005, Seminars in liver disease.

[130]  F. Penin,et al.  Structural Determinants That Target the Hepatitis C Virus Core Protein to Lipid Droplets* , 2006, Journal of Biological Chemistry.

[131]  N. Kato,et al.  Genetic analysis of the hepatitis C virus (HCV) genome from HCV-infected human T cells. , 1997, The Journal of general virology.

[132]  J. O'grady Hepatology: A Textbook of Liver Disease , 1997 .

[133]  N. Kato,et al.  Human hepatocyte clonal cell lines that support persistent replication of hepatitis C virus. , 1998, Virus research.

[134]  S. Lemon,et al.  Production of infectious genotype 1a hepatitis C virus (Hutchinson strain) in cultured human hepatoma cells , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[135]  J. Holland,et al.  RNA virus populations as quasispecies. , 1992, Current topics in microbiology and immunology.

[136]  A. Siddiqui,et al.  Interaction of polypyrimidine tract-binding protein with the 5' noncoding region of the hepatitis C virus RNA genome and its functional requirement in internal initiation of translation , 1995, Journal of virology.

[137]  M. Shapiro,et al.  Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[138]  R. Bartenschlager,et al.  Sequences in the 5′ Nontranslated Region of Hepatitis C Virus Required for RNA Replication , 2001, Journal of Virology.

[139]  N. Kato,et al.  Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro processing analysis. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[140]  R. Bartenschlager,et al.  Complex formation between the NS3 serine-type proteinase of the hepatitis C virus and NS4A and its importance for polyprotein maturation , 1995, Journal of virology.

[141]  E. G. Westaway,et al.  Subgenomic replicons of the flavivirus Kunjin: construction and applications , 1997, Journal of virology.

[142]  Hong Luo,et al.  Oligomeric Interaction of Hepatitis C Virus NS5B Is Critical for Catalytic Activity of RNA-dependent RNA Polymerase* , 2002, The Journal of Biological Chemistry.

[143]  L. Pacini,et al.  The NS2 protein of hepatitis C virus is a transmembrane polypeptide , 1995, Journal of virology.

[144]  R. De Francesco,et al.  Multiple Enzymatic Activities Associated with Recombinant NS3 Protein of Hepatitis C Virus , 1998, Journal of Virology.

[145]  Christophe Combet,et al.  Hepatitis C databases, principles and utility to researchers , 2006, Hepatology.

[146]  R. Cortese,et al.  The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus , 2002, The EMBO journal.

[147]  F. Penin,et al.  Topological changes in the transmembrane domains of hepatitis C virus envelope glycoproteins , 2002, The EMBO journal.

[148]  S. Barik,et al.  Sequential phosphorylation of the phosphoprotein of vesicular stomatitis virus by cellular and viral protein kinases is essential for transcription activation , 1992, Journal of virology.

[149]  H. Thomas,et al.  Expression, purification, and partial characterization of HCV RNA polymerase. , 1997, Biochemical and biophysical research communications.

[150]  K. Shimotohno,et al.  Virion-like structures in HeLa G cells transfected with the full-length sequence of the hepatitis C virus genome , 1995 .

[151]  Z. Zhai,et al.  VISA Is an Adapter Protein Required for Virus-Triggered IFN-β Signaling , 2005 .

[152]  Alan S. Perelson,et al.  Hepatitis C Viral Dynamics in Vivo and the Antiviral Efficacy of Interferon-α Therapy , 1998 .

[153]  J. McKeating,et al.  Hepatitis C virus cell‐cell transmission in hepatoma cells in the presence of neutralizing antibodies , 2007, Hepatology.

[154]  Michael G. Katze,et al.  Control of PKR Protein Kinase by Hepatitis C Virus Nonstructural 5A Protein: Molecular Mechanisms of Kinase Regulation , 1998, Molecular and Cellular Biology.

[155]  Guann-Yi Yu,et al.  Palmitoylation and Polymerization of Hepatitis C Virus NS4B Protein , 2006, Journal of Virology.

[156]  P. Mui,et al.  Enhancement of hepatitis C virus NS3 proteinase activity by association with NS4A-specific synthetic peptides: identification of sequence and critical residues of NS4A for the cofactor activity. , 1996, Virology.

[157]  Volker Brass,et al.  Structural determinants for membrane association and dynamic organization of the hepatitis C virus NS3-4A complex , 2008, Proceedings of the National Academy of Sciences.

[158]  P. Liljeström,et al.  A New Generation of Animal Cell Expression Vectors Based on the Semliki Forest Virus Replicon , 1991, Bio/Technology.

[159]  R. Thomssen,et al.  Low density lipoprotein receptor as a candidate receptor for hepatitis C virus , 1999, Journal of medical virology.

[160]  C. Rice,et al.  CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells , 2009, The Journal of general virology.

[161]  E. V. Makeyev,et al.  A mechanism for initiating RNA-dependent RNA polymerization , 2001, Nature.

[162]  R. Bartenschlager,et al.  Role of the Hepatitis C Virus Core+1 Open Reading Frame and Core cis-Acting RNA Elements in Viral RNA Translation and Replication , 2008, Journal of Virology.

[163]  C. Nardella,et al.  Characterization of the Hepatitis C Virus NS2/3 Processing Reaction by Using a Purified Precursor Protein , 2001, Journal of Virology.

[164]  M. Houghton,et al.  The hepatitis C virus encodes a serine protease involved in processing of the putative nonstructural proteins from the viral polyprotein precursor. , 1993, Biochemical and biophysical research communications.

[165]  M. Lai,et al.  Determination of the secondary structure of and cellular protein binding to the 3'-untranslated region of the hepatitis C virus RNA genome , 1997, Journal of virology.

[166]  K. Shimotohno,et al.  Hepatitis C Virus Non-structural Proteins in the Probable Membranous Compartment Function in Viral Genome Replication* , 2003, Journal of Biological Chemistry.

[167]  S. Iacovacci,et al.  The human bone-marrow-derived B-cell line CE, susceptible to hepatitis C virus infection. , 1993, Research in virology.

[168]  Y. Matsuura,et al.  Interaction of Hepatitis C Virus Core Protein with Viral Sense RNA and Suppression of Its Translation , 1999, Journal of Virology.

[169]  K. Kirkegaard,et al.  Oligomerization and Cooperative RNA Synthesis Activity of Hepatitis C Virus RNA-Dependent RNA Polymerase , 2002, Journal of Virology.

[170]  S. Polyak,et al.  Unique Features of Hepatitis C Virus Capsid Formation Revealed by De Novo Cell-Free Assembly , 2004, Journal of Virology.

[171]  K. Kirkegaard,et al.  Coupling between genome translation and replication in an RNA virus. , 1994, Genes & development.

[172]  Yan-Hwa Wu Lee,et al.  Direct interaction of hepatitis C virus core protein with the cellular lymphotoxin-beta receptor modulates the signal pathway of the lymphotoxin-beta receptor , 1997, Journal of virology.

[173]  M. Ramachandra,et al.  Association between NS3 and NS5 Proteins of Dengue Virus Type 2 in the Putative RNA Replicase Is Linked to Differential Phosphorylation of NS5 (*) , 1995, The Journal of Biological Chemistry.

[174]  C. Rice,et al.  The C Terminus of Hepatitis C Virus NS4A Encodes an Electrostatic Switch That Regulates NS5A Hyperphosphorylation and Viral Replication , 2007, Journal of Virology.

[175]  John McLauchlan,et al.  The Hepatitis C Virus NS4B Protein Can trans-Complement Viral RNA Replication and Modulates Production of Infectious Virus , 2008, Journal of Virology.

[176]  A. Osterhaus,et al.  Identification of a Naturally Occurring Recombinant Genotype 2/6 Hepatitis C Virus , 2006, Journal of Virology.

[177]  G. Seelig,et al.  Enzymatic characterization of hepatitis C virus NS3/4A complexes expressed in mammalian cells by using the herpes simplex virus amplicon system , 1996, Journal of virology.

[178]  R. Yan,et al.  Human hepatitis B virus and hepatocellular carcinoma I. Experimental infection of tree shrews with hepatitis B virus , 2005, Journal of Cancer Research and Clinical Oncology.

[179]  Toshiaki Maruyama,et al.  Complete Replication of Hepatitis C Virus in Cell Culture , 2005, Science.

[180]  R. Cortese,et al.  The solution structure of the N-terminal proteinase domain of the hepatitis C virus (HCV) NS3 protein provides new insights into its activation and catalytic mechanism. , 1999, Journal of molecular biology.

[181]  P. Bouffard,et al.  Hepatitis C virus is detected in a monocyte/macrophage subpopulation of peripheral blood mononuclear cells of infected patients. , 1992, The Journal of infectious diseases.

[182]  F. Penin,et al.  From Structure to Function: New Insights into Hepatitis C Virus RNA Replication* , 2006, Journal of Biological Chemistry.

[183]  M. Katze,et al.  Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein. , 1997, Virology.

[184]  J Frank,et al.  Hepatitis C Virus IRES RNA-Induced Changes in the Conformation of the 40S Ribosomal Subunit , 2001, Science.

[185]  M. Makuuchi,et al.  Enhancement of hepatitis C virus replication by Epstein–Barr virus‐encoded nuclear antigen 1 , 1999, The EMBO journal.

[186]  Joseph D. Puglisi,et al.  The Pathway of HCV IRES-Mediated Translation Initiation , 2004, Cell.

[187]  R. Jackson,et al.  A prokaryotic-like mode of cytoplasmic eukaryotic ribosome binding to the initiation codon during internal translation initiation of hepatitis C and classical swine fever virus RNAs. , 1998, Genes & development.

[188]  C. Rice,et al.  3′ RNA Elements in Hepatitis C Virus Replication: Kissing Partners and Long Poly(U) , 2007, Journal of Virology.

[189]  Colin W Shepard,et al.  Global epidemiology of hepatitis C virus infection. , 2005, The Lancet. Infectious diseases.

[190]  R. Bartenschlager,et al.  Kinetic and structural analyses of hepatitis C virus polyprotein processing , 1994, Journal of virology.

[191]  S. Fukushi,et al.  The sequence element of the internal ribosome entry site and a 25-kilodalton cellular protein contribute to efficient internal initiation of translation of hepatitis C virus RNA , 1997, Journal of virology.

[192]  Volker Brass,et al.  Structure and Function of the Membrane Anchor Domain of Hepatitis C Virus Nonstructural Protein 5A* , 2004, Journal of Biological Chemistry.

[193]  R. Bartenschlager,et al.  Characterization of the Early Steps of Hepatitis C Virus Infection by Using Luciferase Reporter Viruses , 2006, Journal of Virology.

[194]  Steven R. LaPlante,et al.  An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus , 2003, Nature.

[195]  N. Kato,et al.  A novel sequence found at the 3' terminus of hepatitis C virus genome. , 1995, Biochemical and biophysical research communications.

[196]  K. Shimotohno,et al.  Production of two phosphoproteins from the NS5A region of the hepatitis C viral genome. , 1994, Biochemical and biophysical research communications.

[197]  Smita S. Patel,et al.  A Brownian motor mechanism of translocation and strand separation by hepatitis C virus helicase , 2005, Nature Structural &Molecular Biology.

[198]  C. Trépo,et al.  Specific detection of hepatitis C virus minus strand RNA in hematopoietic cells. , 1996, The Journal of clinical investigation.

[199]  R. Purcell,et al.  Nucleotide sequence and mutation rate of the H strain of hepatitis C virus. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[200]  Baohua Gu,et al.  The Nonstructural Protein 3 Protease/Helicase Requires an Intact Protease Domain to Unwind Duplex RNA Efficiently* , 2004, Journal of Biological Chemistry.

[201]  E. Schreier,et al.  Antibodies in human sera specific to hypervariable region 1 of hepatitis C virus can block viral attachment. , 1995, Virology.

[202]  F. Chisari,et al.  Cellular Determinants of Hepatitis C Virus Assembly, Maturation, Degradation, and Secretion , 2007, Journal of Virology.

[203]  S. Kaneko,et al.  RNA-dependent RNA Polymerase Activity of the Soluble Recombinant Hepatitis C Virus NS5B Protein Truncated at the C-terminal Region* , 1998, The Journal of Biological Chemistry.

[204]  A. Howe,et al.  A novel recombinant single‐chain hepatitis C virus ns3‐ns4a protein with improved helicase activity , 1999, Protein science : a publication of the Protein Society.

[205]  Mark Harris,et al.  Hepatitis C virus NS5A: tales of a promiscuous protein. , 2004, The Journal of general virology.

[206]  R. Francesco,et al.  An amino-terminal domain of the hepatitis C virus NS3 protease is essential for interaction with NS4A , 1995, Journal of virology.

[207]  J. Boyer,et al.  Infectious transcripts and cDNA clones of RNA viruses. , 1994, Virology.

[208]  J P Griffith,et al.  Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding. , 1998, Structure.

[209]  M. Gale,et al.  Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. , 2005, Molecular cell.

[210]  Y. Sasaguri,et al.  Hepatitis C virus NS5A protein is phosphorylated in vitro by a stably bound protein kinase from HeLa cells and by cAMP-dependent protein kinase A-α catalytic subunit , 1997 .

[211]  Y. Modis,et al.  Structure of the dengue virus envelope protein after membrane fusion , 2004, Nature.

[212]  M. Houghton,et al.  A quantitative test to estimate neutralizing antibodies to the hepatitis C virus: cytofluorimetric assessment of envelope glycoprotein 2 binding to target cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[213]  N. Nakajima,et al.  Characterization of long-term cultures of hepatitis C virus , 1996, Journal of virology.

[214]  H. Kräusslich,et al.  Analysis of hepatitis C virus core protein interaction domains. , 1997, The Journal of general virology.

[215]  M. Yanagi,et al.  Transcripts of a chimeric cDNA clone of hepatitis C virus genotype 1b are infectious in vivo. , 1998, Virology.

[216]  J. Wands,et al.  Tightly regulated expression of the entire hepatitis C virus structural region in continuous human cell lines. , 1998, Biochemical and biophysical research communications.

[217]  Olga Kalinina,et al.  A Natural Intergenotypic Recombinant of Hepatitis C Virus Identified in St. Petersburg , 2002, Journal of Virology.

[218]  A. Carroll,et al.  Development of a GB Virus B Marmoset Model and Its Validation with a Novel Series of Hepatitis C Virus NS3 Protease Inhibitors , 2004, Journal of Virology.

[219]  Yoon Ki Kim,et al.  Heterogeneous Nuclear Ribonucleoprotein L Interacts with the 3′ Border of the Internal Ribosomal Entry Site of Hepatitis C Virus , 1998, Journal of Virology.

[220]  R. Bartenschlager,et al.  The lipid droplet is an important organelle for hepatitis C virus production , 2007, Nature Cell Biology.

[221]  N. Kato,et al.  Susceptibility of human T-lymphotropic virus type I infected cell line MT-2 to hepatitis C virus infection. , 1995, Biochemical and biophysical research communications.

[222]  P. Sarnow,et al.  Modulation of Hepatitis C Virus RNA Abundance by a Liver-Specific MicroRNA , 2005, Science.

[223]  F. Iber,et al.  Hepatology: A Textbook of Liver Disease , 1983 .

[224]  L. Pacini,et al.  In Vitro Selection and Characterization of Hepatitis C Virus Serine Protease Variants Resistant to an Active-Site Peptide Inhibitor , 2003, Journal of Virology.

[225]  C. Rice,et al.  Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase , 2005, Nature.

[226]  D. Tyrrell,et al.  Hepatitis C virus replication in mice with chimeric human livers , 2001, Nature Medicine.

[227]  S. Sauleda,et al.  The clinical picture of acute and chronic hepatitis C. , 1994, Current studies in hematology and blood transfusion.

[228]  C. Rice,et al.  Hepatitis C virus NS3 serine proteinase: trans-cleavage requirements and processing kinetics , 1994, Journal of virology.

[229]  V. Agnello,et al.  Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[230]  J. Maniloff,et al.  Virus taxonomy : eighth report of the International Committee on Taxonomy of Viruses , 2005 .

[231]  M. Gale,et al.  CARD games between virus and host get a new player. , 2006, Trends in immunology.

[232]  Yoshiharu Matsuura,et al.  The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice , 1998, Nature Medicine.

[233]  J. Mackenzie,et al.  Ultrastructure of Kunjin virus-infected cells: colocalization of NS1 and NS3 with double-stranded RNA, and of NS2B with NS3, in virus-induced membrane structures , 1997, Journal of virology.

[234]  J. Choe,et al.  C-terminal domain of the hepatitis C virus NS3 protein contains an RNA helicase activity. , 1995, Biochemical and biophysical research communications.

[235]  D. Lamarre,et al.  In Vitro Characterization of a Purified NS2/3 Protease Variant of Hepatitis C Virus* , 2001, The Journal of Biological Chemistry.

[236]  R. Bartenschlager,et al.  Mutations in Hepatitis C Virus RNAs Conferring Cell Culture Adaptation , 2001, Journal of Virology.

[237]  Y. Ito,et al.  Genetic drift of hepatitis C virus during an 8.2-year infection in a chimpanzee: variability and stability. , 1992, Virology.

[238]  F. Penin,et al.  The nonstructural 5A protein of hepatitis C virus genotype 1b does not contain an interferon sensitivity-determining region. , 2007, The Journal of infectious diseases.

[239]  R. De Francesco,et al.  Reduction of Hepatitis C Virus NS5A Hyperphosphorylation by Selective Inhibition of Cellular Kinases Activates Viral RNA Replication in Cell Culture , 2004, Journal of Virology.

[240]  M. Gale,et al.  Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[241]  Christophe Combet,et al.  Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes , 2005, Hepatology.

[242]  Ralf Bartenschlager,et al.  Essential Role of Domain III of Nonstructural Protein 5A for Hepatitis C Virus Infectious Particle Assembly , 2008, PLoS pathogens.

[243]  C. Peschle,et al.  Replication and multiplication of hepatitis C virus genome in human foetal liver cells. , 1993, Research in virology.

[244]  A. Gorbalenya,et al.  Viral cysteine proteinases , 1996, Perspectives in drug discovery and design : PD3.

[245]  T. Takegami,et al.  Hepatitis C virus nonstructural protein NS3 transforms NIH 3T3 cells , 1995, Journal of virology.

[246]  H. Yoon,et al.  Domain 2 of nonstructural protein 5A (NS5A) of hepatitis C virus is natively unfolded. , 2007, Biochemistry.

[247]  J. Bergelson,et al.  Virus-Induced Abl and Fyn Kinase Signals Permit Coxsackievirus Entry through Epithelial Tight Junctions , 2006, Cell.

[248]  C. Rice,et al.  Structure of the catalytic domain of the hepatitis C virus NS2-3 protease , 2006, Nature.

[249]  S. Burgess,et al.  Evidence for the Formation of a Heptameric Ion Channel Complex by the Hepatitis C Virus P7 Protein in Vitro* , 2006, Journal of Biological Chemistry.

[250]  R. Bartenschlager,et al.  Nonstructural protein 3 of the hepatitis C virus encodes a serine-type proteinase required for cleavage at the NS3/4 and NS4/5 junctions , 1993, Journal of virology.

[251]  C. Rice,et al.  Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA. , 1997, Science.

[252]  R. Chung,et al.  Heterogeneous nuclear ribonucleoprotein I (hnRNP-I/PTB) selectively binds the conserved 3' terminus of hepatitis C viral RNA. , 1999, Biochemical and biophysical research communications.

[253]  A. Salonen,et al.  Viral RNA Replication in Association with Cellular Membranes , 2005, Current topics in microbiology and immunology.

[254]  M. Aoki,et al.  Host sphingolipid biosynthesis as a target for hepatitis C virus therapy , 2005, Nature chemical biology.

[255]  T. Asselah,et al.  STEATOSIS IN CHRONIC HEPATITIS C: WHY DOES IT REALLY MATTER? , 2005, Gut.

[256]  Charles M. Rice,et al.  The NS5A Protein of Hepatitis C Virus Is a Zinc Metalloprotein* , 2004, Journal of Biological Chemistry.

[257]  K. Shimotohno,et al.  Phosphorylation of hepatitis C virus-encoded nonstructural protein NS5A , 1995, Journal of virology.

[258]  Z. Hong,et al.  De Novo Initiation of RNA Synthesis by Hepatitis C Virus Nonstructural Protein 5B Polymerase , 2000, Journal of Virology.

[259]  E. Blanchard,et al.  Hepatitis C Virus Entry Depends on Clathrin-Mediated Endocytosis , 2006, Journal of Virology.

[260]  Paul Ahlquist,et al.  Host Factors in Positive-Strand RNA Virus Genome Replication , 2003, Journal of Virology.

[261]  W. Stremmel,et al.  Establishment of persistent hepatitis C virus infection and replication in vitro. , 1997, The Journal of general virology.

[262]  S. Levy,et al.  Functional Analysis of Cell Surface-Expressed Hepatitis C Virus E2 Glycoprotein , 1999, Journal of Virology.

[263]  T. Tellinghuisen,et al.  Regulation of Hepatitis C Virion Production via Phosphorylation of the NS5A Protein , 2008, PLoS pathogens.

[264]  L. Bianchi,et al.  Expression of Hepatitis C Virus Proteins Induces Distinct Membrane Alterations Including a Candidate Viral Replication Complex , 2002, Journal of Virology.

[265]  C. Guguen-Guillouzo,et al.  Dynamic analysis of hepatitis C virus replication and quasispecies selection in long-term cultures of adult human hepatocytes infected in vitro. , 1999, The Journal of general virology.

[266]  D. Moradpour,et al.  Hepatitis C virus comes full circle: Production of recombinant infectious virus in tissue culture , 2005, Hepatology.

[267]  A. Tramontano,et al.  A zinc binding site in viral serine proteinases. , 1996, Biochemistry.

[268]  C. Cheng‐Mayer,et al.  Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[269]  T. Fuerst,et al.  Demonstration of in vitro infection of chimpanzee hepatocytes with hepatitis C virus using strand-specific RT/PCR. , 1994, Virology.

[270]  F. Penin,et al.  Structural and Functional Characterization of Nonstructural Protein 2 for Its Role in Hepatitis C Virus Assembly* , 2008, Journal of Biological Chemistry.

[271]  M. Lai,et al.  Homotypic interaction and multimerization of hepatitis C virus core protein. , 1996, Virology.

[272]  J. Arnold,et al.  Hepatitis C Virus Nonstructural Protein 5A (NS5A) Is an RNA-binding Protein* , 2005, Journal of Biological Chemistry.

[273]  A. Shavinskaya,et al.  Construction and characterization of infectious intragenotypic and intergenotypic hepatitis C virus chimeras. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[274]  P. V. van Rijn,et al.  Infectious RNA transcribed from an engineered full-length cDNA template of the genome of a pestivirus , 1996, Journal of virology.

[275]  S. Hirohashi,et al.  Replication of Hepatitis C Virus in Cultured Non‐neoplastic Human Hepatocytes , 1996, Japanese journal of cancer research : Gann.

[276]  B. Kümmerer,et al.  Recovery of cytopathogenic and noncytopathogenic bovine viral diarrhea viruses from cDNA constructs , 1996, Journal of virology.

[277]  R. De Francesco,et al.  Hyperphosphorylation of the Hepatitis C Virus NS5A Protein Requires an Active NS3 Protease, NS4A, NS4B, and NS5A Encoded on the Same Polyprotein , 1999, Journal of Virology.

[278]  Darius Moradpour,et al.  A Dynamic View of Hepatitis C Virus Replication Complexes , 2008, Journal of Virology.

[279]  N. Kato,et al.  Proteolytic processing and membrane association of putative nonstructural proteins of hepatitis C virus. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[280]  Christopher T. Jones,et al.  University of Birmingham Time-and Temperature-Dependent Activation of Hepatitis C Virus for Low-pH-Triggered Entry , 2006 .

[281]  C. Rice,et al.  A second hepatitis C virus-encoded proteinase. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[282]  S. Chu,et al.  Cellular proteins specifically bind to the 5'-noncoding region of hepatitis C virus RNA. , 1995, Virology.

[283]  R. De Francesco,et al.  Hepatitis C Virus NS5A Is a Direct Substrate of Casein Kinase I-α, a Cellular Kinase Identified by Inhibitor Affinity Chromatography Using Specific NS5A Hyperphosphorylation Inhibitors* , 2007, Journal of Biological Chemistry.

[284]  S. Kuge,et al.  Specific interaction of polypyrimidine tract-binding protein with the extreme 3'-terminal structure of the hepatitis C virus genome, the 3'X , 1997, Journal of virology.

[285]  K. Shimotohno,et al.  Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. , 2005, Molecular cell.

[286]  J. Lepault,et al.  Conformational change and protein–protein interactions of the fusion protein of Semliki Forest virus , 2004, Nature.

[287]  W. Zhong,et al.  De NovoInitiation of RNA Synthesis by a Recombinant Flaviridae RNA-dependent RNA Polymerase , 1999 .

[288]  M. Lai,et al.  The 3′-Untranslated Region of Hepatitis C Virus RNA Enhances Translation from an Internal Ribosomal Entry Site , 1998, Journal of Virology.

[289]  Charles A. Lesburg,et al.  Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site , 1999, Nature Structural Biology.

[290]  H. T. Head,et al.  Global surveillance and control of hepatitis C , 1999 .

[291]  N. Kato,et al.  Characterization of hepatitis C virus replication in cloned cells obtained from a human T-cell leukemia virus type 1-infected cell line, MT-2 , 1996, Journal of virology.

[292]  M. Lai,et al.  Interactions between Viral Nonstructural Proteins and Host Protein hVAP-33 Mediate the Formation of Hepatitis C Virus RNA Replication Complex on Lipid Raft , 2004, Journal of Virology.

[293]  Charles M. Rice,et al.  Highly Permissive Cell Lines for Subgenomic and Genomic Hepatitis C Virus RNA Replication , 2002, Journal of Virology.

[294]  C. Rice,et al.  Hepatitis C virus NS3 protein polynucleotide-stimulated nucleoside triphosphatase and comparison with the related pestivirus and flavivirus enzymes , 1993, Journal of virology.

[295]  T. Tsuji,et al.  Ubiquitous presence of cellular proteins that specifically bind to the 3' terminal region of hepatitis C virus. , 1998, Biochemical and biophysical research communications.

[296]  K. Bienz,et al.  Intracellular Localization of Poliovirus Plus- and Minus-Strand RNA Visualized by Strand-Specific Fluorescent In Situ Hybridization , 1998, Journal of Virology.

[297]  R. Purcell,et al.  Evidence for in vitro replication of hepatitis C virus genome in a human T-cell line. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[298]  Osamu Takeuchi,et al.  IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction , 2005, Nature Immunology.

[299]  N. Kato,et al.  Two distinct proteinase activities required for the processing of a putative nonstructural precursor protein of hepatitis C virus , 1993, Journal of virology.

[300]  Jianbo Chen,et al.  A positive-strand RNA virus replication complex parallels form and function of retrovirus capsids. , 2002, Molecular cell.

[301]  M. Su,et al.  The hepatitis C virus NS4A protein: interactions with the NS4B and NS5A proteins , 1997, Journal of virology.

[302]  S. Aihara,et al.  Demonstration of sugar moiety on the surface of hepatitis C virions recovered from the circulation of infected humans. , 1993, Virology.

[303]  M. Honda,et al.  Structural requirements for initiation of translation by internal ribosome entry within genome-length hepatitis C virus RNA. , 1996, Virology.

[304]  E. Nogales,et al.  Structural Roles for Human Translation Factor eIF3 in Initiation of Protein Synthesis , 2005, Science.

[305]  D. Wong,et al.  Hepatitis C Virus Structural Proteins Assemble into Viruslike Particles in Insect Cells , 1998, Journal of Virology.

[306]  J. McLauchlan,et al.  Intramembrane proteolysis promotes trafficking of hepatitis C virus core protein to lipid droplets , 2002, The EMBO journal.

[307]  Chris Sander,et al.  Cellular cofactors affecting hepatitis C virus infection and replication , 2007, Proceedings of the National Academy of Sciences.

[308]  M. Honda,et al.  An infectious molecular clone of a Japanese genotype 1b hepatitis C virus , 1999, Hepatology.

[309]  C. Rice,et al.  Characterization of truncated forms of hepatitis C virus glycoproteins. , 1997, The Journal of general virology.

[310]  M. Mizokami,et al.  Efficient replication of the genotype 2a hepatitis C virus subgenomic replicon. , 2003, Gastroenterology.

[311]  F. Penin,et al.  Hepatitis C Virus Core Protein Is a Dimeric Alpha-Helical Protein Exhibiting Membrane Protein Features , 2005, Journal of Virology.

[312]  S. Boulant,et al.  Disrupting the association of hepatitis C virus core protein with lipid droplets correlates with a loss in production of infectious virus. , 2007, The Journal of general virology.

[313]  R. Purcell,et al.  Correlation between the infectivity of hepatitis C virus in vivo and its infectivity in vitro. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[314]  A. Branch,et al.  Evidence for a functional RNA element in the hepatitis C virus core gene , 2007, Proceedings of the National Academy of Sciences.

[315]  R. Bartenschlager,et al.  Characterization of Cell Lines Carrying Self-Replicating Hepatitis C Virus RNAs , 2001, Journal of Virology.

[316]  C. Rice,et al.  Processing in the hepatitis C virus E2-NS2 region: identification of p7 and two distinct E2-specific products with different C termini , 1994, Journal of virology.

[317]  J. Krijnse-Locker,et al.  Modification of intracellular membrane structures for virus replication , 2008, Nature Reviews Microbiology.

[318]  Sebastian Bonhoeffer,et al.  Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis , 1999, The Lancet.

[319]  M. Yanagi,et al.  Transcripts from a single full-length cDNA clone of hepatitis C virus are infectious when directly transfected into the liver of a chimpanzee. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[320]  N. Kato,et al.  Specific detection of positive and negative stranded hepatitis C viral RNA using chemical RNA modification , 2005, Archives of Virology.

[321]  M. Houghton,et al.  Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. , 1989, Science.

[322]  R. Dwek,et al.  The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[323]  F. Rey,et al.  Structural Analysis of the Hepatitis C Virus RNA Polymerase in Complex with Ribonucleotides , 2002, Journal of Virology.

[324]  A. Nomoto,et al.  Internal ribosome entry site within hepatitis C virus RNA , 1992, Journal of virology.

[325]  V. Serebrov,et al.  Periodic cycles of RNA unwinding and pausing by hepatitis C virus NS3 helicase , 2004, Nature.

[326]  M. Murcko,et al.  Crystal Structure of the Hepatitis C Virus NS3 Protease Domain Complexed with a Synthetic NS4A Cofactor Peptide , 1996, Cell.

[327]  R. Bartenschlager,et al.  Selective Stimulation of Hepatitis C Virus and Pestivirus NS5B RNA Polymerase Activity by GTP* , 1999, The Journal of Biological Chemistry.

[328]  N. Kato,et al.  Two proteinase activities in HCV polypeptide expressed in insect cells using baculovirus vector , 2005, Archives of Virology.

[329]  H. Blum,et al.  Hepatitis B virus infection of tupaia hepatocytes in vitro and in vivo , 1996, Hepatology.

[330]  J. Dubuisson,et al.  Early steps of the hepatitis C virus life cycle , 2008, Cellular microbiology.

[331]  C. Rice,et al.  Identification of the Major Phosphorylation Site of the Hepatitis C Virus H Strain NS5A Protein as Serine 2321* , 1999, The Journal of Biological Chemistry.

[332]  A. Siddiqui,et al.  Translation of human hepatitis C virus RNA in cultured cells is mediated by an internal ribosome-binding mechanism , 1993, Journal of virology.

[333]  E. Galun,et al.  The hepatitis B virus–trimera mouse: A model for human HBV infection and evaluation of anti‐HBV therapeutic agents , 1999, Hepatology.

[334]  S. Emerson,et al.  The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[335]  K. Ishii,et al.  Interaction of Hepatitis C Virus Nonstructural Protein 5A with Core Protein Is Critical for the Production of Infectious Virus Particles , 2008, Journal of Virology.

[336]  C. Rice,et al.  The NS5A/NS5 Proteins of Viruses from Three Genera of the Family Flaviviridae Are Phosphorylated by Associated Serine/Threonine Kinases , 1998, Journal of Virology.

[337]  S. Lemon,et al.  3′ Nontranslated RNA Signals Required for Replication of Hepatitis C Virus RNA , 2003, Journal of Virology.

[338]  D. R. Taylor,et al.  Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. , 1999, Science.

[339]  R. De Francesco,et al.  NS3 is a serine protease required for processing of hepatitis C virus polyprotein , 1993, Journal of virology.

[340]  J. Pawlotsky,et al.  Alpha Interferon Inhibits Hepatitis C Virus Replication in Primary Human Hepatocytes Infected In Vitro , 2002, Journal of Virology.

[341]  N. Kato,et al.  Structure of the 3' terminus of the hepatitis C virus genome , 1996, Journal of virology.

[342]  A. Maerz,et al.  Cell surface expression of functional hepatitis C virus E1 and E2 glycoproteins , 2003, FEBS letters.

[343]  Charles M. Rice,et al.  Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry , 2007, Nature.

[344]  A. Siddiqui,et al.  The La antigen binds 5' noncoding region of the hepatitis C virus RNA in the context of the initiator AUG codon and stimulates internal ribosome entry site-mediated translation. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[345]  M. Ghany,et al.  Diagnosis, management, and treatment of hepatitis C: An update , 2009, Hepatology.

[346]  R. Bartenschlager,et al.  Cell Culture Adaptation of Hepatitis C Virus and In Vivo Viability of an Adapted Variant , 2007, Journal of Virology.

[347]  Roger Williams Global challenges in liver disease , 2006, Hepatology.

[348]  K. Shimotohno,et al.  The N-terminal region of hepatitis C virus nonstructural protein 3 (NS3) is essential for stable complex formation with NS4A , 1995, Journal of virology.

[349]  M. Ichikawa,et al.  The Native Form and Maturation Process of Hepatitis C Virus Core Protein , 1998, Journal of Virology.

[350]  C. Rice,et al.  Phosphorylation of the hepatitis C virus NS5A protein in vitro and in vivo: properties of the NS5A-associated kinase , 1997, Journal of virology.

[351]  S. Lemon,et al.  Mutations Conferring Resistance to SCH6, a Novel Hepatitis C Virus NS3/4A Protease Inhibitor , 2006, Journal of Biological Chemistry.

[352]  C. Rice,et al.  Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[353]  M. Lai,et al.  A Recombinant Hepatitis C Virus RNA-Dependent RNA Polymerase Capable of Copying the Full-Length Viral RNA , 1999, Journal of Virology.

[354]  C. Voisset,et al.  Hepatitis C virus entry: potential receptors and their biological functions. , 2006, The Journal of general virology.

[355]  H. Ago Crystal structure of the RNA-dependent RNA polymerase of hepatitis Cvirus , 1999 .

[356]  D. Burton,et al.  Robust hepatitis C virus infection in vitro. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[357]  F. Penin,et al.  Hepatitis C Virus p7 Protein Is Crucial for Assembly and Release of Infectious Virions , 2007, PLoS pathogens.