Susceptibility of different hepatitis B virus isolates to interferon-alpha in a mouse model based on hydrodynamic injection.

ABSTRACT: Interferon alpha (IFN-?) is commonly used for the treatment of chronic hepatitis B (CHB) patients. Many factors including viral genetics may determine the outcome of IFN-? therapy. In this study, we tested whether the expression of IFN-? directly in the liver inhibits HBV gene expression and replication using a HBV hydrodynamic injection (HI) mouse model. Two replication-competent clones from different HBV isolates that belonging to HBV genotype A and B based on a pAAV vector (pAAV-HBV-A and pAAV-HBV-B) were compared for their susceptibility to IFN-?. HBV clones were injected into mice either alone or in combination with a murine (m) IFN-? expression plasmid (pmIFN-?). HBsAg and HBeAg concentrations and HBV DNA levels in mice differed after injection of these two HBV clones. Co-application of pmIFN-? together with the two distinct isolates resulted in markedly different kinetics of decline of HBsAg, HBeAg, and HBV DNA levels in the mice. Immunohistochemical staining of liver sections with anti-HBc showed that mIFN-? application completely inhibited the expression of HBcAg in mice inoculated with pAAV-HBV-B, whereas the expression of HBcAg was only reduced in mice with pAAV-HBV-A. Consistently, mice injected with pAAV-HBV-B and pmIFN-? showed higher expression levels of the IFN-stimulated genes (ISGs) ISG15, OAS, PKR as well as proinflammatory cytokine IL-6 in the liver. In addition, expression levels of anti-inflammatory cytokine IL-10 was down-regulated significantly in liver of the mice injected with pAAV-HBV-B and pmIFN-?. Our data demonstrate that IFN-? exerts antiviral activity in HBV mouse model, but different HBV isolates may have diverse susceptibility to IFN-?.

SUBMITTER: Song J 

PROVIDER: S-EPMC3950299 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature