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Understanding the hepatitis C virus life cycle paves the way for highly effective therapies

Nature Medicine volume 19, pages 837–849 (2013)Cite this article

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Abstract

More than two decades of intense research has provided a detailed understanding of hepatitis C virus (HCV), which chronically infects 2% of the world's population. This effort has paved the way for the development of antiviral compounds to spare patients from life-threatening liver disease. An exciting new era in HCV therapy dawned with the recent approval of two viral protease inhibitors, used in combination with pegylated interferon-α and ribavirin; however, this is just the beginning. Multiple classes of antivirals with distinct targets promise highly efficient combinations, and interferon-free regimens with short treatment duration and fewer side effects are the future of HCV therapy. Ongoing and future trials will determine the best antiviral combinations and whether the current seemingly rich pipeline is sufficient for successful treatment of all patients in the face of major challenges, such as HCV diversity, viral resistance, the influence of host genetics, advanced liver disease and other co-morbidities.

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Figure 1: Timeline of the milestones in HCV functional and antiviral research.
Figure 2: The HCV genome and polyprotein processing.
Figure 3: The HCV life cycle and points of intervention.

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Acknowledgements

We are grateful to I.M. Jacobson for critical reading of the manuscript. Our research is supported by grants from the US Public Health Service, the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (AI099284, AI072613, AI075099, AI091707, AI090055), Office of the Director through the NIH Roadmap for Medical Research (DK085713), US National Cancer Institute (CA057973), The Rockefeller University Center for Clinical and Translational Science (UL1RR024143), the Center for Basic and Translational Research on Disorders of the Digestive System through the generosity of the Leona M. and Harry B. Helmsley Charitable Trust, the Greenberg Medical Research Institute and the Starr Foundation. T.K.H.S. is supported by a postdoctoral fellowship and a Sapere Aude Research Talent Award from The Danish Council for Independent Research. We apologize to the many HCV investigators whose work could not be cited owing to space restrictions.

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

    Troels K H Scheel & Charles M Rice

  2. Department of Infectious Diseases and Clinical Research Centre, Copenhagen Hepatitis C Program, Copenhagen University Hospital, Hvidovre, Denmark

    Troels K H Scheel

  3. Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Troels K H Scheel

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Correspondence to Charles M Rice.

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C.M.R. declares an equity interest in Apath, which holds commercial rights to HCV-related technology, and has in addition served as a consultant or scientific advisor to Genentech, GlaxoSmithKline, iTherX, Merck & Co. Inc. and Novartis. C.M.R. and T.K.H.S. both hold patent rights to HCV-related technology.

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Scheel, T., Rice, C. Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nat Med 19, 837–849 (2013). https://doi.org/10.1038/nm.3248

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