Hot-spot mutations in hepatitis B virus core gene: eliciting or evading immune clearance?

The biological implications of substitutions L60V and I97L in the core (c) gene of hepatitis B virus (HBV) were investigated in order to determine whether they could change the immunogenicity of HBcAg or influence the immune response in mice. Three strains of recombinant adenoviruses--AdHBV-WT, AdHBV-L60V and AdHBV-I97L--containing wild-type or mutant HBV genomes were constructed using the AdEasy system and used to infect BALB/c mice intranasally. Infected mice produced anti-HBc efficiently to comparable levels. IgG1 and IgG2a specific for HBcAg were present in mice sera, and the response was dominated by IgG2a. The lymphocyte proliferative response specific for HBcAg was assessed by [3H]-thymidine uptake. We found that AdHBV-WT induced a stronger T-cell proliferation response than AdHBV-L60V and AdHBV-I97L. In conclusion, the L60V and I97L substitutions had no influence on humoral immune responses, but could downregulate T-cell responses to HBcAg, suggesting that L60V and I97L were immune escape mutants.