Interferons alpha and beta (IFN alpha and IFN beta) are type I interferons produced by the host to control pathogen propagation. However, only a minority of chronic hepatitis B (CHB) patients generate a sustained response after treatment with recombinant IFN alpha. The anti-HBV effect of IFN beta and the underlying mechanism are not well -understood. Here, we compared the antiviral activities of IFN alpha and IFN beta by application of IFNa or IFN beta expression plasmids using the well -established HBV hydrodynamic injection (HI) mouse model. Injection of IFN alpha expression plasmid could significantly reduce HBV serum markers including HBsAg, HBeAg and HBV DNA as well as the number of HBcAg positive cells in the liver, while IFN beta showed only a weak inhibition of HBV replication. In contrast to IFN beta, IFN alpha resulted in elevated expression levels of IFN stimulated genes (ISGs) as well as the proinflammatory cytokine interleukin 6 (IL6) in the liver. Moreover, IFN beta treated mice showed higher expression levels of the anti-inflammatory cytolcines 1L10 and TGF beta in the liver compared to IFN alpha. Our results demonstrated that both IFN alpha and IFN beta exert antiviral activities against HBV in HI mouse model, but IFNa is more effective than IFN beta. (C) 2016 Elsevier GmbH. All rights reserved.