Replicative efficiency and pathogenicity of hepatitis B virus e‐minus precore variant

To study the replicative efficiency and pathogenicity of hepatitis B virus precore variant (A1896), anti‐hepatitis B virus e antigen (HBe) titre was studied in naturally occurring wild‐type virus infection, A1896 variant infection and dual infection. Higher titre of anti‐HBe was found in patients with no virus replication and in patients coinfected with the wild‐type virus and A1896 variant, which suggest that anti‐HBe may either act as an inhibitor of virus replication or as selective pressure for the A1896 variant. Three site‐directed mutants were constructed in the duck hepatitis B virus (DHBV) precore region. A frame shift in the encapsidation signal region abolished replication of DHBV; mutation in the initiation codon of the precore and mutation to generate a termination codon at the distal region of the precore resulted in decreased replication in the duck model. More significant pathological changes were found in the liver tissues of ducks infected with the mutant which mimicked the HBV A1896 variant.