| Literature DB >> 12021368 |
William R Addison1, Kathie-Anne Walters, Winnie W S Wong, John S Wilson, Danuta Madej, Lawrence D Jewell, D Lorne J Tyrrell.
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.Entities:
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Year: 2002 PMID： 12021368 PMCID： PMC136192 DOI： 10.1128/jvi.76.12.6356-6363.2002
Source DB: PubMed Journal: J Virol ISSN： 0022-538X Impact factor: 5.103