Hepatitis A and Hepatitis C Viruses: Divergent Infection Outcomes Marked by Similarities in Induction and Evasion of Interferon Responses

Lin Qu; Stanley M Lemon

doi:10.1055/s-0030-1267534

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2010; 30(4): 319-332
DOI: 10.1055/s-0030-1267534

Hepatitis A and Hepatitis C Viruses: Divergent Infection Outcomes Marked by Similarities in Induction and Evasion of Interferon Responses

Lin Qu¹ , Stanley M. Lemon¹

¹Division of Infectious Diseases, Department of Medicine, Center for Translational Research, Inflammatory Diseases Institute, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Abstract

ABSTRACT

Hepatitis A and hepatitis C viruses (HAV and HCV) are both positive-strand ribonucleic acid (RNA) viruses with hepatotropic lifestyles. Despite several important differences, they share many biological and molecular features and similar genome replication schemes. Despite this, HAV infections are usually effectively controlled by the host with elimination of the virus, whereas HCV most often is able to establish lifelong persistent infection. The mechanisms underlying this difference are unknown. The cellular helicases RIG-I and MDA5, and Toll-like receptor 3, are pattern recognition receptors that sense virus-derived RNAs within hepatocytes in the liver. Activation of these receptors leads to their interaction with specific adaptor proteins, mitochondrial antiviral signaling protein (MAVS) and TIR-domain-containing adapter-inducing interferon-β (TRIF), respectively, which engage downstream kinases to activate two crucial transcription factors, nuclear factor kappa B (NF-κB) and interferon regulatory factor 3 (IRF3). This results in the induction of interferons (IFNs) and IFN-stimulated genes that ultimately establish an antiviral state. These signaling pathways are central to host antiviral defense and thus frequent targets for viral interference. Both HAV and HCV express proteases that target signal transduction through these pathways and that block the induction of IFNs upon sensing of viral RNA by these receptors. An understanding of the differences and similarities in the early innate immune responses to these infections is likely to provide important insights into the mechanism underlying the long-term persistence of HCV.

KEYWORDS

Hepatitis C virus - hepatitis A virus - interferon

Full Text

References

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Stanley M LemonM.D.

Division of Infectious Diseases, Department of Medicine, Center for Translational Research, Inflammatory Diseases Institute

Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295

Email: smlemon@UTMB.EDU

Email: stanley_lemon@med.unc.edu