Hepatitis C Virus

Hepatitis C virus is a positive-sense ribonucleic acid virus that is parenterally transmitted and is associated with chronic liver disease – fibrosis, cirrhosis and liver failure. It is a leading indicator for both liver transplant surgery and the development of hepatocellular carcinoma. Treatment is limited to a combination of interferon and ribavirin and is only partially effective. Research into the biology of hepatitis C virus has been hampered until recently by the inability to propagate the virus in cell culture. However, this obstacle has now been overcome and there is now a new momentum that promises to reveal much about this virus, hopefully leading to new and more effective therapies.

Keywords: hepatitis; virus; blood; RNA replication; pathogenesis

Figure 1. Structure of the HCV genome and subgenomic replicon. The top part of the figure shows the location of the individual HCV proteins within the polyprotein. The numbering refers to the amino acid residues corresponding to junctions between each protein (numbering based on the genotype 1b infectious clone J4: genbank accession number: AF054247). The putative structures of the 5¢ and 3¢ UTRs are depicted. In the typical subgenomic replicon presented in the lower part of the figure, the sequence encoding Core through to the junction between NS2 and NS3 is replaced by the coding sequence for a marker gene and a second IRES (derived from the picornavirus, Encephalomyocarditis virus: EMCV).
Figure 2. Membrane topology of the HCV proteins. The predicted topology of the 10 mature proteins derived from the HCV polyprotein is depicted. The barrels represent transmembrane helices (apart from those in NS4A and NS5A where they are amphipathic helices, thus only contacting the membrane via one face of the helix). Note the C-terminal transmembrane helix of the Core is cleaved within the membrane by signal peptide peptidase. N- and C-termini are indicated to orientate the proteins in the membrane.
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 Further Reading
    Barth H, Liang TJ and Baumert TF (2006) Hepatitis C virus entry: molecular biology and clinical implications. Hepatology 44: 527–535.
    Choo QL, Kuo G, Weiner AJ et al. (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non- B viral-hepatitis genome. Science 244: 359–362.
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    Kuiken C, Combet C, Bukh J et al. (2006) A comprehensive system for consistent numbering of HCV sequences, proteins and epitopes. Hepatology 44: 1355–1361.
    Tedbury PR and Harris M (2007) Characterisation of the role of zinc in the hepatitis C virus NS2/3 auto-cleavage and NS3 protease activities. Journal of Molecular Biology 366: 1652–1660.
    Tellinghuisen TL, Marcotrigiano J and Rice CM (2005) Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase. Nature 435: 374–379.
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Harris, Mark(Dec 2007) Hepatitis C Virus. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001028.pub2]