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 singl e amino acid change in the human immunodeficiency virus reverse transc riptase is responsible for high-level resistance to this compound. Duc k hepatitis B virus mutants were created bearing the analogous amino a cid change in the duck hepatitis B virus polymerase. Viral DNA product ion was reduced 92% for the wild-type virus at 2 mu g of lamivudine pe r ml, while the mutants required 40 mu g of lamivudine per ml to inhib it replication by greater than 80%.