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Journal of Virology, June 2002, p. 6356-6363, Vol. 76, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.12.6356-6363.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Half-Life of the Duck Hepatitis B Virus Covalently Closed Circular DNA Pool In Vivo following Inhibition of Viral Replication

William R. Addison,1* Kathie-Anne Walters,1 Winnie W. S. Wong,2 John S. Wilson,1 Danuta Madej,1 Lawrence D. Jewell,3 and D. Lorne J. Tyrrell1,2

Department of Medical Microbiology and Immunology and Glaxo Wellcome Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2,1 Department of Medicine,2 Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada T6G 2R73

Received 10 January 2002/ Accepted 16 March 2002

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.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, 622 HMRC, University of Alberta, Edmonton, Alberta, Canada T6G 2S2. Phone: (780) 492-7227. Fax: (780) 492-9828. E-mail: bill.addison{at}ualberta.ca.

Journal of Virology, June 2002, p. 6356-6363, Vol. 76, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.12.6356-6363.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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