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
Author(s) -
Karl P. Fischer,
D L Tyrrell
Publication year - 1996
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.40.8.1957
Subject(s) - lamivudine , virology , biology , hepatitis b virus , polymerase , hepatitis b virus dna polymerase , virus , hepadnaviridae , duck hepatitis b virus , dna polymerase , reverse transcriptase , viral replication , mutagenesis , orthohepadnavirus , mutant , microbiology and biotechnology , polymerase chain reaction , dna , gene , biochemistry
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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