Half-life of the Duck Hepatitis B Virus Covalently Closed Circular DNA Pool in Vivo Following Inhibition of Viral Replication

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2002 May 22

PMID 12021368

Citations 44

Authors

William R Addison

Kathie-Anne Walters

Winnie W S Wong

John S Wilson

Danuta Madej

Lawrence D Jewell

D Lorne J Tyrrell

Affiliations

Soon will be listed here.

Abstract

Covalently closed circular DNA (cccDNA) is a crucial intermediate in the replication of hepadnaviruses. We inhibited the replication of duck hepatitis B virus in congenitally infected ducks with a combination of lamivudine and a dideoxyguanosine prodrug. Inhibition of viral replication should prevent renewal of the cccDNA pool, and its decay was measured in liver biopsy samples collected over a 5-month period. In three ducks, the cccDNA pools declined exponentially, with half-lives ranging from 35 to 57 days. In two others, the pools declined exponentially for about 70 days but then stabilized at about 6 copies/diploid genome. The selection of drug-resistant virus mutants is an unlikely explanation for this unexpected stabilization of cccDNA levels. Liver sections stained for the cell division marker PCNA showed that animals in which cccDNA loss was continuous had significantly greater numbers of PCNA-positive nuclei than did those animals in which cccDNA levels had plateaued.

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