Hepatitis B virus variants with lamivudine-related mutations in the DNA polymerase and the 'a' epitope of the surface antigen are sensitive to ganciclovir

Lamivudine is a new antiviral agent effective against hepatitis B viral (HBV) infections but can result in virus-drug resistance associated with mutations in the conserved 'YM₅₅₂DD' motif of the HBV DNA polymerase. Due to their overlapping coding regions in the HBV genome, mutations in the DNA polymerase may result in substitutions in the hepatitis B surface antigen (HBsAg), albeit outside the antigenic 'a' epitope. Here we report the identification of a novel type of lamivudine-related mutations located in both the polymerase (YM₅₅₂DD→YI₅₅₂DD) and the 'a' epitope of HBsAg (Gly₁₃₀→Asp₁₃₀). The same virus carried a HBsAg Gly₁₄₅→Arg₁₄₅ mutation prior to therapy. Both the wild type HBV and lamivudine-related mutants with the Gly₁₄₅→Arg₁₄₅ HBsAg mutation were suppressed following ganciclovir treatment, indicating a beneficial additive effect of both drugs against different forms of HBV mutants. Copyright (C) 1999 Elsevier Science B.V.