The antiviral effects of human microRNA miR-302c-3p against hepatitis B virus infection

Background Conventional treatments of chronic hepatitis B virus (HBV) infection rarely achieve a decline of serum hepatitis B surface antigen (HBsAg) levels and eradication of the virus. Aim To elucidate the antiviral mechanisms of a human microRNA, miR-302c-3p, against HBV replication. Methods The antiviral effect of miR-302c-3p was evaluated in vitro and in vivo by transfecting the miR-302c-3p mimic into HBV-infected HepG2-hNTCP-C4 cells and HBV transgenic mice respectively. Results miR-302c-3p decreased not only HBV replication but also production of HBsAg. Pregenomic RNA and HBsAg mRNA concentrations decreased in the cells treated with miR-302c-3p. Interestingly, the amount of cccDNA was significantly reduced in the miR-302c-3p-treated cells, in association with disappearance of the HBV core protein. An RNA immunoprecipitation assay showed that miR-302c-3p decreased the binding of the HBV polymerase to the pregenomic RNA by hybridising with the epsilon-loop region. A number of host genes were downregulated in miR-302c-3p-treated cells, including BMPR2 and HNF4A. Knockdown of these two genes by corresponding siRNAs also suppressed HBV replication and HBsAg secretion. The antiviral effect of miR-302c-3p was also observed in HBV transgenic mice. Conclusion miR-302c-3p had anti-HBV activity, in vitro and in vivo, via several mechanisms.