PURPOSE: To investigate the effectiveness of an interferon administration on different genotypes of hepatitis B virus (HBV) in vitro and in vivo. METHODS: In vitro, we transfected plasmids carrying different HBV genotypes including recently identified new genotype I into HepG2 and HuH7 cells, then treated with standard interferon alpha (IFN-α); in vivo, we treated mice with pegylated interferon alpha (Peg-IFN-α) after injection with HBV DNA of different genotypes. The culture supernatants from cell culture and sera from mice were collected and used in hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) assays by ELISA and HBV DNA measurement by PCR. RESULTS: Both in cell culture and in mouse model, it was observed that HBV genotypes A and B exhibited significantly better response to IFN-α2a or Peg-IFN-α2a in terms of reduced expression of HBsAg, HBeAg and the HBV DNA level as compared to HBV genotypes C and D. Moreover, the inhibitory effect of IFN-α2a or Peg-IFN-α2a on HBV genotype I was greater than on genotype C or D, but less than genotype A. However, there was no significant response difference between genotypes A and B, C and D, B and I, respectively. CONCLUSION: The effectiveness of IFN/Peg-IFN to suppress HBV replication is dependent on different HBV genotypes. IFN/Peg-IFN is more effective on HBV genotype A or B than on genotype C, D or I. Treatment regimens are suggested to be adapted to HBV genotype.
PURPOSE: To investigate the effectiveness of an interferon administration on different genotypes of hepatitis B virus (HBV) in vitro and in vivo. METHODS: In vitro, we transfected plasmids carrying different HBV genotypes including recently identified new genotype I into HepG2 and HuH7 cells, then treated with standard interferon alpha (IFN-α); in vivo, we treated mice with pegylated interferon alpha (Peg-IFN-α) after injection with HBV DNA of different genotypes. The culture supernatants from cell culture and sera from mice were collected and used in hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) assays by ELISA and HBV DNA measurement by PCR. RESULTS: Both in cell culture and in mouse model, it was observed that HBV genotypes A and B exhibited significantly better response to IFN-α2a or Peg-IFN-α2a in terms of reduced expression of HBsAg, HBeAg and the HBV DNA level as compared to HBV genotypes C and D. Moreover, the inhibitory effect of IFN-α2a or Peg-IFN-α2a on HBV genotype I was greater than on genotype C or D, but less than genotype A. However, there was no significant response difference between genotypes A and B, C and D, B and I, respectively. CONCLUSION: The effectiveness of IFN/Peg-IFN to suppress HBV replication is dependent on different HBV genotypes. IFN/Peg-IFN is more effective on HBV genotype A or B than on genotype C, D or I. Treatment regimens are suggested to be adapted to HBV genotype.
Authors: Carolina Souza Gusatti; Cintia Costi; Maria Laura Halon; Tarciana Grandi; Arlete Ferrari Rech Medeiros; Cláudia Maria Dornelles Silva; Selma Andrade Gomes; Marcia Susana Nunes Silva; Christian Niel; Maria Lucia Rosa Rossetti Journal: PLoS One Date: 2015-08-14 Impact factor: 3.240