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Antimicrobial Agents and Chemotherapy, Aug 1996, 1957-1960, Vol 40, No. 8
Copyright © 1996 by the American Society for Microbiology. All rights reserved.

Generation of duck hepatitis B virus polymerase mutants through site- directed mutagenesis which demonstrate resistance to lamivudine [(--)- beta-L-2', 3'-dideoxy-3'-thiacytidine] in vitro

KP Fischer and DL Tyrrell
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.

Hepatitis B virus replication is very sensitive to lamivudine. A single amino acid change in human immunodeficiency virus reverse transcriptase is responsible for high-level resistance to this compound. Duck hepatitis B virus mutants were created bearing the analogous amino acid change in the duck hepatitis B virus polymerase. Viral DNA production was reduced 92% for the wild-type virus at 2 micrograms of lamivudine per ml, while the mutants required 40 micrograms of lamivudine per ml to inhibit replication by greater than 80%.

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