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Mechanisms of HCV survival in the host

Nature Reviews Gastroenterology & Hepatology volume 6, pages 217–227 (2009)Cite this article

Abstract

HCV infection is an important cause of liver disease worldwide—nearly 80% of infected patients develop chronic liver disease, which leads to the development of liver cirrhosis and hepatocellular carcinoma. The ability of HCV to persist within a host is believed to be related to the numerous mechanisms by which it evades the immune response of the host. These mechanisms can be divided into defensive and offensive strategies. Examples of defensive mechanisms include replication within enclosed structures, which provides protection from the host's antiviral defenses, genetic diversity created by inaccurate replication, which yields mutants resistant to the cell's antiviral strategies, and association of the virion with protective lipoproteins. Offensive mechanisms include virally encoded proteins and other factors that disrupt the ability of the host cells to detect the virus and downregulate its ability to respond to interferon, impair innate immune defense mechanisms and alter T-cell responses, and prevent the development of an effective B-cell-mediated humoral response. Greater understanding of these viral survival strategies will ultimately translate into more effective antiviral therapies and better prognosis for patients.

Key Points

  • At each stage of the life cycle of the virus, HCV interfaces with antiviral mechanisms of the host

  • Multiple, individual viral proteins inhibit key, cellular, antiviral defense pathways

  • HCV infection is associated with impairment of virtually all parts of the adaptive immune system, although our understanding of the mechanistic details remains incomplete

  • New therapeutic strategies are emerging that seek to translate this knowledge into improved outcomes

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Figure 1: Viral life cycle and major host cell defense pathways.
Figure 2: Innate immune signaling pathways interdicted by HCV.

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Acknowledgements

This work was supported by a Burroughs Wellcome Fund Clinical Scientist Award in Translational Research (JS Glenn), NIH RO1 DK066793, NIH RO1 DK064223 and the Center for Translational Research in Chronic Viral Infections. EH Sklan is the recipient of an ALF Postdoctoral Research Fellow Award and an Israel Science Foundation Bikura Post-doctoral Fellowship. PS Pang is the recipient of a Dean's Fellowship.

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  1. Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, CA, USA

    Prista Charuworn & Jeffrey S. Glenn

  2. Division of Infectious Diseases, Stanford University School of Medicine, CA, USA

    Philip S. Pang

  3. Department of Clinical Immunology and Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Ella H. Sklan

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Correspondence to Jeffrey S. Glenn.

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JS Glenn declared associations with the following companies: Eiger Pharmaceuticals, Epiphany Biosciences, Genentech, Presidio Pharmaceuticals, and Romark Laboratories. The other authors declared no competing interests.

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Sklan, E., Charuworn, P., Pang, P. et al. Mechanisms of HCV survival in the host. Nat Rev Gastroenterol Hepatol 6, 217–227 (2009). https://doi.org/10.1038/nrgastro.2009.32

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