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Review

Hepatitis B virus molecular biology and pathogenesis

R. Jason Lamontagne 1,2 , Sumedha Bagga , Michael J. Bouchard 1
1
1 Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
2 The Wistar Institute, Philadelphia, PA 19104, USA.

ABSTRACT
As obligate intracellular parasites, viruses need a host cell to provide a milieu favorable to viral replication. Consequently,
viruses often adopt mechanisms to subvert host cellular signaling processes. While beneficial for the viral replication cycle,
virus-induced deregulation of host cellular signaling processes can be detrimental to host cell physiology and can lead
to virus-associated pathogenesis, including, for oncogenic viruses, cell transformation and cancer progression. Included
among these oncogenic viruses is the hepatitis B virus (HBV). Despite the availability of an HBV vaccine, 350-500 million
people worldwide are chronically infected with HBV, and a significant number of these chronically infected individuals will
develop hepatocellular carcinoma (HCC). Epidemiological studies indicate that chronic infection with HBV is the leading risk
factor for the development of HCC. Globally, HCC is the second highest cause of cancer-associated deaths, underscoring
the need for understanding mechanisms that regulate HBV replication and the development of HBV-associated HCC.
HBV is the prototype member of the Hepadnaviridae family; members of this family of viruses have a narrow host range
and predominately infect hepatocytes in their respective hosts. The extremely small and compact hepadnaviral genome,
the unique arrangement of open reading frames, and a replication strategy utilizing reverse transcription of an RNA
intermediate to generate the DNA genome are distinguishing features of the Hepadnaviridae. In this review, the authors
provide a comprehensive description of HBV biology, summarize the model systems used for studying HBV infections,
and highlight potential mechanisms that link a chronic HBV-infection to the development of HCC. For example, the HBV
X protein (HBx), a key regulatory HBV protein that is important for HBV replication, is thought to play a cofactor role in the
development of HBV-induced HCC, and the authors highlight the functions of HBx that may contribute to the development
of HBV-associated HCC.
Key words: Hepatitis B virus; hepatocellular carcinoma; hepatitis B virus life cycle; hepatitis B virus-associated disease

Address for correspondence:
Dr. Michael J. Bouchard, Drexel University College of Medicine, 245 N. 15th Street, Philadelphia, PA 19102, USA.
E-mail: michael.bouchard@drexelmed.edu

Received: 01-03-2016, Accepted: 21-04-2016

INTRODUCTION cause of post-transfusion hepatitis. Recognition that
[3]
the Australia antigen was a marker of viral hepatitis
The discovery by Baruch Blumberg and colleagues of facilitated the generation of a blood-screening protocol
the Australia antigen, which would later be identified as that led to a two- to three-fold reduction in the incidence
the hepatitis B virus (HBV) surface antigen, was a major of post-transfusion hepatitis, with the remaining cases
[4]
breakthrough towards improving global health. [1,2] For likely caused by hepatitis C virus (HCV), which would not
decades prior to Blumberg’s discovery, an unknown virus be identified for another 23 years. Retrospective studies
[5]
in blood and plasma samples had been the suspected
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DOI: How to cite this article: Lamontagne RJ, Bagga S, Bouchard MJ.
10.20517/2394-5079.2016.05 Hepatitis B virus molecular biology and pathogenesis. Hepatoma Res
2016;2:163-86.

© 2016 Hepatoma Research | Published by OAE Publishing Inc. 163