Molecular Virology and the Development of Resistant Mutants: Implications for Therapy (original) (raw)

Semin Liver Dis 2005; 25: 9-19
DOI: 10.1055/s-2005-915645

1Professor, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Australia

Publication History

Publication Date:
16 August 2005 (online)

ABSTRACT

Two of the key events in the viral life cycle of the hepatitis B virus (HBV) involve (1) generation from genomic DNA of the covalently closed circular DNA transcriptional template and (2) reverse transcription of the viral pregenomic RNA to form the HBV DNA genome. Because the virus employs reverse transcription to copy its genome, mutant viral genomes are found frequently. Particular selection pressures, both endogenous (host immune clearance) and exogenous (vaccines and antivirals), readily select out these escape mutants. The introduction of nucleoside/nucleotide analogue therapy has seen the emergence of drug resistance as the major factor limiting drug efficacy. The development of drug resistance is not unexpected if viral replication continues in the setting of ongoing treatment, especially monotherapy. Thus, prevention of resistance requires the adoption of strategies that effectively control virus replication.

KEYWORDS

Reverse transcription - covalently closed circular DNA - viral mutants - drug resistance - vaccine escape

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Professor
Stephen Locarnini

Victorian Infectious Diseases Reference Laboratory

10 Wreckyn Street, North Melbourne

Victoria 3051, Australia

Email: stephen.locarnini@mh.org.au