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Semin Liver Dis 2019; 39(03): 301-314
DOI: 10.1055/s-0039-1685518
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Hepatitis B Virus–Hepatocyte Interactions and Innate Immune Responses: Experimental Models and Molecular Mechanisms

Emmanuel Thomas
1   Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida
2   Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida
3   Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida
,
Thomas F. Baumert
4   Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France
5   Laboratory of Excellence HEPSYS, University of Strasbourg, Strasbourg, France
6   Institut Hospitalo-Universitaire, Pôle hépato-digestif, Nouvel Hôpital Civil, Strasbourg, France
› Author Affiliations
Funding E.T. acknowledges support from the NIH (R35GM124915) and Florida Department of Health Bankhead-Coley Cancer Research Program (7BC03). T.F.B. acknowledges support from the European Union (ERC-AdG-HEPCIR, ERC-PoC-2016-PRELICAN, and EU H2020-667273-HEPCAR) ARC, Paris and Institut Hospitalo-Universitaire, Strasbourg (TheraHCC IHUARC IHU201301187), U Strasbourg Foundation HEPKIN, the National Institutes of Health (NCI 1R21CA209940-01A1, NIAID R03AI131066, and NIAID 5U19AI123862-02), and the Institut Universitaire de France (IUF). This work has been published under the framework of the LABEX ANR-10-LABX-0028_HEPSYS and benefits from funding from the state managed by the French National Research Agency as part of the Investments for the Future Program.
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Publication History

Publication Date:
02 July 2019 (online)

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Abstract

Chronic hepatitis B virus (HBV) infection is a major cause of liver disease and cancer worldwide. While current therapeutic approaches can efficiently control viral infection, efficient curative antivirals are absent. The understanding of virus–hepatocyte interactions and sensing of viral infection is an important prerequisite for the development of novel antiviral therapies for cure. Hepatocyte intrinsic innate immunity provides a rapid first line of defense to combat viral infection through the upregulation of antiviral and inflammatory genes. However, the functional relevance of many of these antiviral signaling pathways in the liver and their role in HBV pathogenesis is still only partially understood. The recent identification of intracellular RNA and DNA sensing pathways and their involvement in disease biology, including viral pathogenesis and carcinogenesis, is currently transforming our understanding of virus–host interactions. Here the authors review the current knowledge on intrinsic antiviral innate immune responses including the role of viral nucleic acid sensing pathways in the liver. Since HBV has been designated as a “stealth virus,” the study of the impact of HBV on signaling pathways in the hepatocyte is of significant interest to understand viral pathogenesis. Characterizing the mechanism underlying these HBV–host interactions and targeting related pathways to enhance antiviral innate responses may open new strategies to trigger noncytopathic clearance of covalently closed circular DNA to ultimately cure patients with chronic HBV infection.

Keywords

hepatitis b virus - chemokines - cytokines - antiviral immune responses - IRF3 - nuclear factor-kappaB - pattern recognition receptor - host defense - intrinsic innate responses

Author Contributions

Paper concept, design, and drafting of the manuscript by E.T. and T.F.B.