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.
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%.
Fischer
K P
KP
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
Tyrrell
D L
DL
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D004352:Drug Resistance, Microbial; D015611:Hepatitis B Virus, Duck / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D019259:Lamivudine / Q000494:pharmacology*; D016297:Mutagenesis, Site-Directed; D012194:RNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase; D004259:DNA-Directed DNA Polymerase