CTL escape mutations of core protein are more frequent in strains of HBeAg negative patients with low levels of HBV DNA

BackgroundRecent studies have suggested that Cytotoxic T lymphocytes (CTL) play a key role in eliminating hepatitis B virus (HBV).ObjectivesWe aimed to investigate the role of mutations in different immune epitopes of hepatitis B core antigen (HBcAg) among Iranians with hepatitis B e antigen negative chronic hepatitis B (e-CHB), and asymptomatic carriers (ASCs).Study designAmino acids 1–150 of HBcAg were characterized for HBV strains from 29 e-CHB patients and 48 ASCs from Iran. All patients were infected with HBV genotype D and had previously been investigated for the presence of pre-core and basic core promoter (BCP) mutants.ResultsAmino acid mutations of core protein were observed more frequently in HBV strains from ASCs than e-CHB patients (p = 0.014). Asn67 mutation was mutually exclusive to the combination Ile66 and Ser69 (P < 0.001). Substitutions for Ser21 and Thr12Ser were associated with lower serum levels of HBV DNA (p < 0.001). None of the patients with mutations in HLA-A2 CTL epitope, 18–27, had serum HBV DNA more than 105 copies/mL (p < 0.001). By multivariate analysis, high level (>105 copies/mL) of serum HBV DNA was inversely associated with the presence of mutations in CTL epitopes of HBc (OR: 0.11, p = 0.015), while it was directly associated with the presence of promoter double T1762A1764 mutations together with G1757 (OR: 16.87, p = 0.004).ConclusionThe inverse correlation between serum levels of HBV DNA and CTL escape mutations of the core protein in HBeAg seroconverted patients, supports the notion that selection of CTL escape mutations consolidates the persistence of HBV infection despite reducing viral fitness.