Antiviral Effects Of Different MIFNα Subtypes In A HBV Hydrodynamic Injection Mouse Model

Objective:1. Investigate the antiviral effect of different mIFNα subtypes in a HBVhydrodynamic injection mouse model.2. Explore the possible mechanism underling the distinct antiviral effect of mIFNαsubtypes against HBV infection.3. Provide experimental basis for developing novel antiviral drugs for clinicalantiviral therapy of chronic HBV infection.Methods:1. HBV replication-competent mouse model was established by hydrodynamicinjection (HI) of pAAV-HBV1.2into the tail veins of BALB/c mice. The micewere treated by intraperitoneal injection with mIFNα1、α2、α4、α5、α6、α9、α11recombinant protein, separately, from1day before hydrodynamic injection to8day after injection. The mice injected with saline solution used as control.2. After injection, blood samples were collected from the orbital of the mice on1,4,7and10day post injection (dpi). On the4and10dpi,3~5mice per group weresacrificed and their liver tissue were collected for further experiment. Serum HBsAg, HBeAg, HBsAb, HBeAb and HBcAb levels were detected by ELISA.The expression of HBcAg in liver tissue was detected by immunohistochemicalstaining. The HBV DNA, OAS and PKR mRNA levels in mice were detected byReal Time-PCR.3. Data were analysed by Statistical Package for Sciences (SPSS) version17.0.Statistical method is analysis of variance.With P <0.05for the difference wasstatistically significant. The figures were made by Graphpad Prism5software.Results:1. The result has shown that in HBV HI mouse model, mIFNα5was most effectiveto inhibit expression of serum HBsAg, HBeAg and HBV DNA than othersubtypes, whereas mIFNα11did not significantly inhibit HBV replication andexpression.2. In HBV HI mouse model, mIFNα treatment had no obvious influence on theexpression of HBsAb, HBeAb and HBcAb in mice sera.3. In HBV HI mouse model, mIFNα5was most effective to inhibit expression ofHBcAg and replication of HBV DNA in the liver than other subtypes, whereasmIFNα11was least effective.4. The HBV DNA levels were decreased along with the upregulation of mRNAlevels of OAS in mIFNα4and α5treated groups.Conclusion:1. In HBV hydrodynamic injection mouse model, mIFNα5was most effectivetoinhibit the expression of serum HBsAg, HBeAg, HBV DNA, as well as theexpression of HBcAg and replication of HBV DNA in the liver than othersubtypes, whereas mIFNα11did not significantly inhibit HBV replication and expression.2. The antiviral mechanism of different mIFNα subtypes against HBV was stillunclear, it maybe associate with the expression of PKR and OAS, further researchis needed to disclose the antiviral mechanism of mIFNα subtypes.