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Molecular genetics of HBV infection

Stephen Locarnini, Fabien Zoulim

Corresponding author name: Stephen Locarnini
Corresponding author e-mail: Stephen.Locarnini@mh.org.au

Citation: Antiviral Therapy 2010; 15 Suppl 3: 3-14
doi: 10.3851/IMP1619

Date accepted: 15 February 2010
Date published online: 12 August 2010

Abstract

HBV has evolved a unique life cycle that results in the production of enormous viral loads during active replication without actually killing the infected cells directly. Two of the key events in the viral life cycle of HBV involve firstly the generation of a covalently closed circular (ccc)DNA transcriptional template, either from input genomic DNA or newly replicated capsid-associated DNA, and secondly, reverse transcription of the viral pregenomic (pg)RNA to form progeny HBV DNA genomes. New data are emerging regarding the epigenetic control of cccDNA, which might represent another key factor involved in the pathogenesis and natural history of the disease. Because HBV uses reverse transcription to copy its genome, mutant viral genomes emerge frequently. Particular selection pressures, both endogenous (host immune clearance) and exogenous (vaccines and antiviral drugs), readily select out these escape mutants. The particular viral mutations or combination of mutations that directly affect the clinical outcome of infection are not known; however, four major ‘pathways’ of antiviral drug resistance-associated substitutions have now been identified. Further studies are clearly needed to identify the pathogenetic basis and clinical sequelae arising from the selection of these particular mutants. In the clinical context of antiviral drug resistance, treating physicians need to adopt therapeutic strategies that effectively control viral replication. Finally, the role of host genetics in influencing the outcome of HBV disease in the context of natural history and therapy is beginning to aid understanding in pathogenesis and, when this knowledge is linked to pathogen-specific databases, this should translate into more individualized patient care.

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