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Replication of hepatitis C virus

Nature Reviews Microbiology volume 5, pages 453–463 (2007)Cite this article

Key Points

  • Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide.

  • HCV is classified in the Hepacivirus genus within the Flaviviridae family. These enveloped positive-strand RNA viruses express their structural and non-structural proteins by the translation of a single long open reading frame.

  • HCV cell entry is a complex multistep process involving numerous cellular factors, including scavenger receptor class B type I, CD81 and claudin-1.

  • HCV structural proteins include the core protein and the envelope glycoproteins E1 and E2. The non-structural proteins include the p7 ion channel, the NS2–3 protease, the NS3 serine protease and RNA helicase, the NS4A polypeptide, the NS4B and NS5A proteins, and the NS5B RNA-dependent RNA polymerase.

  • HCV RNA replication takes place in a membrane-associated replication complex.

  • The recent development of complete cell-culture systems now allows the systematic dissection of the entire viral lifecycle.

Abstract

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.

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Figure 1: Lifecycle of hepatitis C virus (HCV).
Figure 2: Current model for hepatitis C virus (HCV) entry.
Figure 3: Genetic organization and polyprotein processing of hepatitis C virus (HCV).
Figure 4: Structures and membrane association of hepatitis C virus (HCV) proteins.
Figure 5: Hepatitis C virus (HCV) replication complex.

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Acknowledgements

Research in the authors' laboratories is supported by the Swiss National Science Foundation, the Swiss Cancer League/Oncosuisse, the Leenaards Foundation, the European Commission, the French Centre National de la Recherche Scientifique, the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales, the US Public Health Service, the Greenberg Medical Research Institute, the Starr Foundation and the Ellison Medical Foundation. We dedicate this Review to the memory of Glovanni Migliaccio, a wonderful scientist and friend, who made many contributions to the HCV field.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, CH-1011, Switzerland

    Darius Moradpour

  2. Institut de Biologie et Chimie des Protéines, UMR 5086, CNRS, Université de Lyon, IFR 128 BioSciences Lyon-Gerland, Lyon, F-69397, France

    François Penin

  3. Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, 10021, New York, USA

    Charles M. Rice

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  1. Darius Moradpour
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Correspondence to Darius Moradpour.

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Competing interests

C.M.R. declares an equity interest in Apath, LLC, which holds commercial rights to the Huh-7.5 cells and other HCV-related technology.

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Moradpour, D., Penin, F. & Rice, C. Replication of hepatitis C virus. Nat Rev Microbiol 5, 453–463 (2007). https://doi.org/10.1038/nrmicro1645

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