Hepatitis C virus


Hepatitis C virus is a positive‐sense RNA virus that is parenterally transmitted and is associated with chronic liver disease – fibrosis, cirrhosis, liver failure and hepatocellular carcinoma. The virus infects an estimated 123 million individuals worldwide with 5 million new infections occurring per annum. The prevalence of the virus, and the persistent nature of the infection, has led to the prediction that it will become an ever‐increasing burden on global healthcare resources. There is no vaccine to prevent infection; however, treatment options, until recently limited to a combination of interferon and ribavirin, have been improved by the advent of direct‐acting antivirals. These therapeutic advances have been underpinned by recent developments in our understanding of the molecular biology of virus infection, which are described in this article. In particular, the establishment of a system for the study of the complete virus lifecycle in tissue culture has led to many major advances and provides opportunities for further therapeutic developments.

Key Concepts:

  • Hepatitis C virus (HCV) is a major human pathogen infecting approximately 3% of the world population.

  • HCV causes chronic liver disease – fibrosis, cirrhosis and hepatocellular carcinoma.

  • HCV is a positive‐strand RNA virus that infects hepatocytes in the liver.

  • Recent developments in HCV biology have allowed a deeper understanding of mechanisms of replication and pathogenesis.

  • New direct‐acting antiviral compounds promise to improve therapeutic options.

Keywords: hepatitis; virus; blood; RNA replication; direct‐acting antivirals

Figure 1.

Structure of the HCV genome and subgenomic replicon (SGR). 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 secondary structures of the 5′ and 3′ UTRs are depicted. In the typical SGR presented in the lower part of the figure, the sequence encoding Core to the junction between NS2 and NS3 is replaced by the coding sequence for a marker gene (X) and a second IRES (derived from the picornavirus, Encephalomyocarditis virus: EMCV). X=typically neomycin phosphotransferase or firefly luciferase. More recently, a fusion of the two genes that retains both activities has been extensively used (termed Feo).

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, NS5A and the N‐ and C‐termini of NS4B, where they are amphipathic helices, thus contacting the membrane only via one face of the helix). Note that the C‐terminal transmembrane helix of Core is cleaved within the membrane by signal peptide peptidase. N‐ and C‐termini are indicated to orientate the proteins in the membrane. Structures are shown where available – PDB entries NS2 (2HD0), NS3/4A (1CU1), NS5A domain I (1ZH1) and NS5B (1C2P).



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Harris, Mark(Apr 2014) Hepatitis C virus. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001028.pub3]