Structural biology of hepatitis C virus.

Hepatitis C virus (HCV) causes acute and chronic liver disease in humans, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Studies of this virus have been hampered by the lack of a productive cell culture system; most information thus has been obtained from analysis of the HCV genome, heterologous expression systems, in vitro and in vivo models, and structural analyses. Structural analyses of HCV components provide an essential framework for understanding of the molecular mechanisms of HCV polyprotein processing, RNA replication, and virion assembly and may contribute to a better understanding of the pathogenesis of hepatitis C. Moreover, these analyses should allow the identification of novel targets for antiviral intervention and development of new strategies to prevent and combat viral hepatitis. This article reviews the current knowledge of HCV structural biology.

[1]  D. R. Taylor,et al.  Hepatitis C virus RNA polymerase and NS5A complex with a SNARE-like protein. , 1999, Virology.

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

[3]  R. Purcell,et al.  A hyperimmune serum against a synthetic peptide corresponding to the hypervariable region 1 of hepatitis C virus can prevent viral infection in cell cultures. , 1996, Virology.

[4]  S. Watowich,et al.  Self-Assembly of Nucleocapsid-Like Particles from Recombinant Hepatitis C Virus Core Protein , 2001, Journal of Virology.

[5]  T. Kodama,et al.  Hepatitis C virus core protein binds to a C-terminal region of NS5B RNA polymerase. , 2002, Hepatology research : the official journal of the Japan Society of Hepatology.

[6]  F. Rey,et al.  Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  M. Kohara,et al.  Hepatitis C virus particle detected by immunoelectron microscopic study. , 1994, The Journal of general virology.

[8]  A. Helenius,et al.  Folding of Hepatitis C Virus E1 Glycoprotein in a Cell-Free System , 2001, Journal of Virology.

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

[10]  M. Lai,et al.  Hepatitis C viral RNA: challenges and promises , 2001, Cellular and Molecular Life Sciences CMLS.

[11]  B. Walker,et al.  Hepatitis C virus infection. , 2001, The New England journal of medicine.

[12]  N. Habuka,et al.  Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. , 1999, Structure.

[13]  A. Kwong,et al.  Structure and function of hepatitis C virus NS3 helicase. , 2000, Current topics in microbiology and immunology.

[14]  M. Lai,et al.  Hepatitis C virus core protein: possible roles in viral pathogenesis. , 2000, Current topics in microbiology and immunology.

[15]  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 .

[16]  C. Rice,et al.  Overview of hepatitis C virus genome structure, polyprotein processing, and protein properties. , 2000, Current topics in microbiology and immunology.

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

[18]  U. Georgopoulou,et al.  Alternate Translation Occurs within the Core Coding Region of the Hepatitis C Viral Genome* , 2002, The Journal of Biological Chemistry.

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

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

[21]  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.

[22]  F. Penin,et al.  Charged Residues in the Transmembrane Domains of Hepatitis C Virus Glycoproteins Play a Major Role in the Processing, Subcellular Localization, and Assembly of These Envelope Proteins , 2000, Journal of Virology.

[23]  J. McLauchlan,et al.  Properties of the hepatitis C virus core protein: a structural protein that modulates cellular processes , 2000, Journal of viral hepatitis.

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

[25]  A. Thiele,et al.  Density heterogeneities of hepatitis C virus in human sera due to the binding of β-lipoproteins and immunoglobulins , 1993, Medical Microbiology and Immunology.

[26]  Y. Sasaguri,et al.  The amino terminal deletion mutants of hepatitis C virus nonstructural protein NS5A function as transcriptional activators in yeast. , 1997, Biochemical and biophysical research communications.

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

[28]  J. Dubuisson,et al.  Biogenesis of hepatitis C virus envelope glycoproteins. , 2001, The Journal of general virology.

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

[30]  J. McLauchlan,et al.  Sequence motifs required for lipid droplet association and protein stability are unique to the hepatitis C virus core protein. , 2000, The Journal of general virology.

[31]  J. McLauchlan,et al.  The Domains Required to Direct Core Proteins of Hepatitis C Virus and GB Virus-B to Lipid Droplets Share Common Features with Plant Oleosin Proteins* , 2002, The Journal of Biological Chemistry.

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

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

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

[35]  N. Kato,et al.  Characterization of hypervariable regions in the putative envelope protein of hepatitis C virus. , 1992, Biochemical and biophysical research communications.

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

[37]  F. Penin,et al.  The Transmembrane Domains of Hepatitis C Virus Envelope Glycoproteins E1 and E2 Play a Major Role in Heterodimerization* , 2000, The Journal of Biological Chemistry.

[38]  J. Pawlotsky Hepatitis C virus resistance to antiviral therapy , 2000, Hepatology.

[39]  D. Stump,et al.  Evidence for a new hepatitis C virus antigen encoded in an overlapping reading frame. , 2001, RNA.

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

[41]  S. Lemon,et al.  Internal ribosome entry site-mediated translation in hepatitis C virus replication. , 2000, Current topics in microbiology and immunology.

[42]  M. Esumi,et al.  Monoclonal antibodies to the hypervariable region 1 of hepatitis C virus capture virus and inhibit virus adsorption to susceptible cells in vitro. , 2000, Virology.

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

[44]  M. Lai,et al.  Hepatitis C virus NS5A colocalizes with the core protein on lipid droplets and interacts with apolipoproteins. , 2002, Virology.

[45]  J. Dubuisson Folding, assembly and subcellular localization of hepatitis C virus glycoproteins. , 2000, Current topics in microbiology and immunology.

[46]  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.

[47]  Anna Tramontano,et al.  A model for the hepatitis C virus envelope glycoprotein E2 , 2000, Proteins.

[48]  C. Rice,et al.  Determinants for Membrane Association of the Hepatitis C Virus RNA-dependent RNA Polymerase* , 2001, The Journal of Biological Chemistry.

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

[50]  P. Simmonds,et al.  Viral heterogeneity of the hepatitis C virus. , 1999, Journal of hepatology.

[51]  C. Englert,et al.  Characterization of cell lines allowing tightly regulated expression of hepatitis C virus core protein. , 1996, Virology.

[52]  S. Emerson,et al.  Hepatitis C virus lacking the hypervariable region 1 of the second envelope protein is infectious and causes acute resolving or persistent infection in chimpanzees. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[53]  M. Kohara,et al.  Hepatitis C virus core particle detected by immunoelectron microscopy and optical rotation technique. , 2001, Hepatology research : the official journal of the Japan Society of Hepatology.

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

[55]  C. Rice,et al.  Interaction between hepatitis C virus proteins and host cell factors. , 2002, Current opinion in microbiology.

[56]  S. Harrison,et al.  The envelope glycoprotein from tick-borne encephalitis virus at 2 Å resolution , 1995, Nature.

[57]  E. Holmes,et al.  A proposed system for the nomenclature of hepatitis C viral genotypes , 1994, Hepatology.

[58]  R. De Francesco,et al.  Structure and function of the hepatitis C virus NS3-NS4A serine proteinase. , 2000, Current topics in microbiology and immunology.

[59]  C. Hagedorn,et al.  Hepatitis C virus RNA-dependent RNA polymerase (NS5B polymerase). , 2000, Current topics in microbiology and immunology.

[60]  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.

[61]  T. Harada,et al.  E2-p7 Region of the Bovine Viral Diarrhea Virus Polyprotein: Processing and Functional Studies , 2000, Journal of Virology.

[62]  N. Kato Molecular virology of hepatitis C virus. , 2001, Acta medica Okayama.

[63]  P. Gounon,et al.  Nonenveloped Nucleocapsids of Hepatitis C Virus in the Serum of Infected Patients , 2001, Journal of Virology.

[64]  M. Lai,et al.  Detection of a Novel Unglycosylated Form of Hepatitis C Virus E2 Envelope Protein That Is Located in the Cytosol and Interacts with PKR , 2002, Journal of Virology.

[65]  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.

[66]  G. Barber,et al.  Hepatitis C Virus Nonstructural 5A Protein Induces Interleukin-8, Leading to Partial Inhibition of the Interferon-Induced Antiviral Response , 2001, Journal of Virology.

[67]  S D Fuller,et al.  Molecular organization of a recombinant subviral particle from tick-borne encephalitis virus. , 2001, Molecular cell.

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

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

[70]  Zhenming Xu,et al.  Synthesis of a novel hepatitis C virus protein by ribosomal frameshift , 2001, The EMBO journal.

[71]  T. Gojobori,et al.  Classification, nomenclature, and database development for hepatitis C virus (HCV) and related viruses: proposals for standardization , 1998, Archives of Virology.

[72]  S. Mishiro,et al.  p26 protein and 33-nm particle associated with nucleocapsid of hepatitis C virus recovered from the circulation of infected hosts. , 1992, Virology.

[73]  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.

[74]  Walker,et al.  Hepatitis C virus: an overview of current approaches and progress. , 1999, Drug discovery today.

[75]  R. Bartenschlager,et al.  Novel cell culture systems for the hepatitis C virus. , 2001, Antiviral research.

[76]  M. Kohara,et al.  Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

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

[78]  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.

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

[80]  T. Braciale,et al.  Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation. , 2000, The Journal of clinical investigation.

[81]  L. Pacini,et al.  Copyright © 1997, American Society for Microbiology In Vitro Study of the NS2-3 Protease of Hepatitis C Virus , 1997 .

[82]  S. Levy,et al.  In search of hepatitis C virus receptor(s). , 2001, Clinics in liver disease.

[83]  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.

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

[85]  F Tsuda,et al.  The entire nucleotide sequences of three hepatitis C virus isolates in genetic groups 7-9 and comparison with those in the other eight genetic groups. , 1998, The Journal of general virology.

[86]  C. Rice,et al.  Isolation and Characterization of Noncytopathic Pestivirus Mutants Reveals a Role for Nonstructural Protein NS4B in Viral Cytopathogenicity , 2001, Journal of Virology.

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

[88]  M. Katze,et al.  How hepatitis C virus counteracts the interferon response: the jury is still out on NS5A. , 2001, Virology.

[89]  A. Weiner,et al.  Sequence variation in hepatitis C viral isolates. , 1991, Journal of hepatology.

[90]  M. Kohara,et al.  Hepatitis C virus core protein binds to apolipoprotein AII and its secretion is modulated by fibrates , 1999, Hepatology.

[91]  C. Rice,et al.  The hepatitis C virus nonstructural protein 4B is an integral endoplasmic reticulum membrane protein. , 2001, Virology.

[92]  Volker Brass,et al.  An Amino-terminal Amphipathic α-Helix Mediates Membrane Association of the Hepatitis C Virus Nonstructural Protein 5A* , 2002, The Journal of Biological Chemistry.

[93]  A. Sherker,et al.  Specific in vitro association between the hepatitis C viral genome and core protein , 1999, Journal of medical virology.

[94]  J. Ou,et al.  Membrane Topology of the Hepatitis C Virus NS2 Protein* , 2002, The Journal of Biological Chemistry.

[95]  P. André,et al.  Characterization of Low- and Very-Low-Density Hepatitis C Virus RNA-Containing Particles , 2002, Journal of Virology.

[96]  D. Rowlands,et al.  The internal ribosome entry site (IRES) of hepatitis C virus visualized by electron microscopy. , 2001, RNA.

[97]  W. Syu,et al.  Self-association of the C-terminal domain of the hepatitis-C virus core protein. , 1998, European Journal of Biochemistry.

[98]  M. Katze,et al.  Evading the interferon response: hepatitis C virus and the interferon-induced protein kinase, PKR. , 2000, Current topics in microbiology and immunology.

[99]  Luis Carrasco Modification of membrane permeability by animal viruses. , 1989, Pharmacology & therapeutics.

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