Immunobiology and pathogenesis of hepatitis B virus infection

Hepatitis B virus (HBV) is a non-cytopathic, hepatotropic virus with the potential to cause a persistent infection, ultimately leading to cirrhosis and hepatocellular carcinoma. Over the past four decades, the basic principles of HBV gene expression and replication as well as the viral and host dete...

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Published in:	Nature reviews. Immunology Vol. 22; no. 1; pp. 19 - 32
Main Authors:	Iannacone, Matteo, Guidotti, Luca G
Format:	Journal Article
Language:	English
Published:	England Nature Publishing Group 01.01.2022
Subjects:	Adaptive immunity CD8 antigen CD8-Positive T-Lymphocytes Cell differentiation Chronic infection Cirrhosis Fibrosis Gene expression Genomes Hemodynamics Hepatitis Hepatitis B Hepatitis B surface antigen Hepatitis B virus - genetics Hepatitis B, Chronic - pathology Hepatocellular carcinoma Humans Immune clearance Immune response Infections Inflammation Liver cancer Liver cirrhosis Liver diseases Liver Neoplasms - etiology Lymphocytes Lymphocytes T Pathogenesis Viruses
ISSN:	1474-1733, 1474-1741, 1474-1741
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Abstract	Hepatitis B virus (HBV) is a non-cytopathic, hepatotropic virus with the potential to cause a persistent infection, ultimately leading to cirrhosis and hepatocellular carcinoma. Over the past four decades, the basic principles of HBV gene expression and replication as well as the viral and host determinants governing infection outcome have been largely uncovered. Whereas HBV appears to induce little or no innate immune activation, the adaptive immune response mediates both viral clearance as well as liver disease. Here, we review our current knowledge on the immunobiology and pathogenesis of HBV infection, focusing in particular on the role of CD8 T cells and on several recent breakthroughs that challenge current dogmas. For example, we now trust that HBV integration into the host genome often serves as a relevant source of hepatitis B surface antigen (HBsAg) expression during chronic infection, possibly triggering dysfunctional T cell responses and favouring detrimental immunopathology. Further, the unique haemodynamics and anatomy of the liver - and the changes they frequently endure during disease progression to liver fibrosis and cirrhosis - profoundly influence T cell priming, differentiation and function. We also discuss why therapeutic approaches that limit the intrahepatic inflammatory processes triggered by HBV-specific T cells might be surprisingly beneficial for patients with chronic infection.
AbstractList	Hepatitis B virus (HBV) is a non-cytopathic, hepatotropic virus with the potential to cause a persistent infection, ultimately leading to cirrhosis and hepatocellular carcinoma. Over the past four decades, the basic principles of HBV gene expression and replication as well as the viral and host determinants governing infection outcome have been largely uncovered. Whereas HBV appears to induce little or no innate immune activation, the adaptive immune response mediates both viral clearance as well as liver disease. Here, we review our current knowledge on the immunobiology and pathogenesis of HBV infection, focusing in particular on the role of CD8+ T cells and on several recent breakthroughs that challenge current dogmas. For example, we now trust that HBV integration into the host genome often serves as a relevant source of hepatitis B surface antigen (HBsAg) expression during chronic infection, possibly triggering dysfunctional T cell responses and favouring detrimental immunopathology. Further, the unique haemodynamics and anatomy of the liver - and the changes they frequently endure during disease progression to liver fibrosis and cirrhosis - profoundly influence T cell priming, differentiation and function. We also discuss why therapeutic approaches that limit the intrahepatic inflammatory processes triggered by HBV-specific T cells might be surprisingly beneficial for patients with chronic infection.Hepatitis B virus (HBV) is a non-cytopathic, hepatotropic virus with the potential to cause a persistent infection, ultimately leading to cirrhosis and hepatocellular carcinoma. Over the past four decades, the basic principles of HBV gene expression and replication as well as the viral and host determinants governing infection outcome have been largely uncovered. Whereas HBV appears to induce little or no innate immune activation, the adaptive immune response mediates both viral clearance as well as liver disease. Here, we review our current knowledge on the immunobiology and pathogenesis of HBV infection, focusing in particular on the role of CD8+ T cells and on several recent breakthroughs that challenge current dogmas. For example, we now trust that HBV integration into the host genome often serves as a relevant source of hepatitis B surface antigen (HBsAg) expression during chronic infection, possibly triggering dysfunctional T cell responses and favouring detrimental immunopathology. Further, the unique haemodynamics and anatomy of the liver - and the changes they frequently endure during disease progression to liver fibrosis and cirrhosis - profoundly influence T cell priming, differentiation and function. We also discuss why therapeutic approaches that limit the intrahepatic inflammatory processes triggered by HBV-specific T cells might be surprisingly beneficial for patients with chronic infection. Hepatitis B virus (HBV) is a non-cytopathic, hepatotropic virus with the potential to cause a persistent infection, ultimately leading to cirrhosis and hepatocellular carcinoma. Over the past four decades, the basic principles of HBV gene expression and replication as well as the viral and host determinants governing infection outcome have been largely uncovered. Whereas HBV appears to induce little or no innate immune activation, the adaptive immune response mediates both viral clearance as well as liver disease. Here, we review our current knowledge on the immunobiology and pathogenesis of HBV infection, focusing in particular on the role of CD8 T cells and on several recent breakthroughs that challenge current dogmas. For example, we now trust that HBV integration into the host genome often serves as a relevant source of hepatitis B surface antigen (HBsAg) expression during chronic infection, possibly triggering dysfunctional T cell responses and favouring detrimental immunopathology. Further, the unique haemodynamics and anatomy of the liver - and the changes they frequently endure during disease progression to liver fibrosis and cirrhosis - profoundly influence T cell priming, differentiation and function. We also discuss why therapeutic approaches that limit the intrahepatic inflammatory processes triggered by HBV-specific T cells might be surprisingly beneficial for patients with chronic infection. Hepatitis B virus (HBV) is a non-cytopathic, hepatotropic virus with the potential to cause a persistent infection, ultimately leading to cirrhosis and hepatocellular carcinoma. Over the past four decades, the basic principles of HBV gene expression and replication as well as the viral and host determinants governing infection outcome have been largely uncovered. Whereas HBV appears to induce little or no innate immune activation, the adaptive immune response mediates both viral clearance as well as liver disease. Here, we review our current knowledge on the immunobiology and pathogenesis of HBV infection, focusing in particular on the role of CD8+ T cells and on several recent breakthroughs that challenge current dogmas. For example, we now trust that HBV integration into the host genome often serves as a relevant source of hepatitis B surface antigen (HBsAg) expression during chronic infection, possibly triggering dysfunctional T cell responses and favouring detrimental immunopathology. Further, the unique haemodynamics and anatomy of the liver — and the changes they frequently endure during disease progression to liver fibrosis and cirrhosis — profoundly influence T cell priming, differentiation and function. We also discuss why therapeutic approaches that limit the intrahepatic inflammatory processes triggered by HBV-specific T cells might be surprisingly beneficial for patients with chronic infection.In this Review, Iannacone and Guidotti discuss the immunobiology and pathogenesis of hepatitis B virus (HBV) infection, with a particular focus on the role of CD8+ T cells, and examine recent breakthroughs that challenge current dogmas.
Author	Guidotti, Luca G Iannacone, Matteo
Author_xml	– sequence: 1 givenname: Matteo orcidid: 0000-0002-9370-2671 surname: Iannacone fullname: Iannacone, Matteo email: iannacone.matteo@hsr.it, iannacone.matteo@hsr.it, iannacone.matteo@hsr.it organization: Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy. iannacone.matteo@hsr.it – sequence: 2 givenname: Luca G orcidid: 0000-0002-0205-2678 surname: Guidotti fullname: Guidotti, Luca G email: guidotti.luca@hsr.it, guidotti.luca@hsr.it organization: Vita-Salute San Raffaele University, Milan, Italy. guidotti.luca@hsr.it
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/34002067$$D View this record in MEDLINE/PubMed
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ContentType	Journal Article
Copyright	2021. Springer Nature Limited. Springer Nature Limited 2021.
Copyright_xml	– notice: 2021. Springer Nature Limited. – notice: Springer Nature Limited 2021.
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Snippet	Hepatitis B virus (HBV) is a non-cytopathic, hepatotropic virus with the potential to cause a persistent infection, ultimately leading to cirrhosis and...
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SubjectTerms	Adaptive immunity CD8 antigen CD8-Positive T-Lymphocytes Cell differentiation Chronic infection Cirrhosis Fibrosis Gene expression Genomes Hemodynamics Hepatitis Hepatitis B Hepatitis B surface antigen Hepatitis B virus - genetics Hepatitis B, Chronic - pathology Hepatocellular carcinoma Humans Immune clearance Immune response Infections Inflammation Liver cancer Liver cirrhosis Liver diseases Liver Neoplasms - etiology Lymphocytes Lymphocytes T Pathogenesis Viruses
Title	Immunobiology and pathogenesis of hepatitis B virus infection
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