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.