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

Area of Science:

• Virology
• Hepatology
• Molecular Biology

Background:

• Hepatitis B virus (HBV) precore variants can influence viral replication and disease progression.
• The A1896 variant is associated with altered viral kinetics and immune response.
• Understanding the replicative efficiency and pathogenicity of HBV variants is crucial for therapeutic strategies.

Purpose of the Study:

• To investigate the replicative efficiency and pathogenicity of the hepatitis B virus precore variant A1896.
• To determine the role of anti-hepatitis B virus e antigen (HBe) titre in the context of wild-type HBV, A1896 variant, and dual infections.
• To assess the impact of specific mutations in the duck hepatitis B virus (DHBV) precore region on viral replication and pathogenesis.

Main Methods:

• Studied anti-HBe titres in patients with wild-type HBV, A1896 variant, and dual infections.
• Constructed three site-directed mutants in the DHBV precore region.
• Infected ducks with mutant DHBV strains to evaluate replication and pathogenicity.

Main Results:

• Higher anti-HBe titres were observed in patients with no viral replication and in those coinfected with wild-type HBV and the A1896 variant.
• A frameshift mutation in the DHBV encapsidation signal region abolished replication.
• Mutations in the precore initiation codon or generating a termination codon decreased DHBV replication, with enhanced pathological changes in liver tissues.

Conclusions:

• Anti-HBe may inhibit HBV replication or act as selective pressure for the A1896 variant.
• Specific mutations in the precore region significantly impair viral replication, as demonstrated in the DHBV model.
• The HBV A1896 variant exhibits reduced replicative efficiency and potentially increased pathogenicity, highlighting the importance of precore region integrity.