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Immunologic Signatures of Rejection pp 127–140Cite as

Innate Signatures of Immune Mediated Resolution and Persistence of Hepatitis C Virus Infections

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Abstract

Hepatitis C Virus infections have a high propensity to induce lifelong persistent infections. A number of host and environmental variables have been shown to impact the rate of persistent infection and the outcome of interferon (IFN)-based therapies. This review briefly highlights a few of the relevant observations that have been made with regard to viral clearance. HCV infection induces a highly elevated interferon stimulated gene (ISG) response in the liver during both acute and chronic infections. The role of this response in containing the spread of the virus in the liver and in mounting an effective adaptive immune response is poorly understood. The fact that an elevated hepatic ISG response during chronic infection negatively correlates with the outcome of IFN therapy is counter-intuitive and remains to be explained satisfactorily. The failure of the T cell response to clear virus appears to reside in a deficiency in the CD4 T cell help leading to anergic CD8 T cells, which may also be related to whether the innate response properly orchestrates the adaptive T cell response early in infection. The importance of the innate response in the outcome of infection is illustrated by recent genome wide association studies revealing a remarkable correlation between genetic polymorphisms in IL28B (IFNλ3) and clearance of infected cells whether during acute infection or IFN therapy, yet the mechanisms by which IFNλ3 and other innate effectors influence HCV infection are currently poorly understood.

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Authors and Affiliations

  1. Department of Virology and Immunology, Southwest Foundation for Biomedical Research and Southwest National Primate Research Center, 7620 NW Loop 410, San Antonio, TX, 78227, USA

    Robert E. Lanford

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  1. Robert E. Lanford
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Correspondence to Robert E. Lanford .

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Editors and Affiliations

  1. Clinical Center, Dept. Transfusion Medicine, National Institute of Health (NIH), Center Drive 10, Bethesda, 20892-1502, Maryland, USA

    Francesco M. Marincola

  2. National Institutes of Health Bldg 10, Bethesda, 20892, Maryland, USA

    Ena Wang

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Lanford, R.E. (2011). Innate Signatures of Immune Mediated Resolution and Persistence of Hepatitis C Virus Infections. In: Marincola, F., Wang, E. (eds) Immunologic Signatures of Rejection. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7219-4_9

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