The response of hepatitis B virus genotype to interferon is associated with a mutation in the interferon-stimulated response element

Genetic variation and genotype of Hepatitis B virus (HBV) are related to the efficiency of interferon alpha (IFN-alpha)-based antiviral therapy. However, the correlation of variation in interferon-stimulated response element (ISRE) and HBV genotype response to IFN-alpha therapy remains elusive. Differences of ISRE between genotype B and C HBV were explored using the HBV sequences retrieved from GenBank, and further investigated by ISRE region cloning and sequencing from 60 clinical samples post-IFN-alpha therapy. Additionally, ISRE mutants were constructed and their relation to responsiveness of IFN-alpha was evaluated by real-time PCR and Southern blot analysis. ISRE pattern between genotype B and C were found based on both clinical sample sequencing and full-length sequence alignment. The primary difference is the fourth base within the ISRE region, with T and C for genotype B and C, respectively. HBV with genotype C-type ISRE had a higher replicative capability as compared to HBV with genotype B-type ISRE after IFN-alpha treatment in huh7 cells. Conclusion: Preference of ISRE between genotype B and C HBV are distinct. Single nucleotide difference (C to T) within the HBV ISRE region may link to the efficacy of IFN-alpha therapy to genotype B and C HBV. Therefore, this study provides a clue for the determination of IFN-alpha therapy response to HBV treatment.