Human MxA protein participates to the interferon-related inhibition of hepatitis B virus replication in female transgenic mice

Background/Aims The interferon (IFN) inducible MxA protein is endowed with antiviral activity against a broad range of RNA viruses. In a previous in vitro study, we demonstrated that MxA inhibits hepatitis B virus (HBV) replication, arguing that the antiviral activity of MxA is not restricted to RNA viruses but also includes a DNA virus. The aim of the present study was to further demonstrate in vivo the antiviral action of MxA against HBV. Methods We generated HBV and HBV/MxA transgenic mice lacking a functional IFN-α/β receptor and thus constituting a good model to evaluate MxA-induced virus resistance. HBV proteins expression, viral load and HBV replication were compared in HBV and HBV/MxA mice. Results An MxA-dependent moderate inhibitory effect on HBV expression was only observed in female HBV/MxA mice, in which MxA downregulates (i) viral HBeAg and capsid protein expression, (ii) viremia and (iii) HBV replication by decreasing the synthesis of HBV DNA replicative intermediates. Furthermore, these effects were not associated with changes to steady-state levels of HBV RNAs. Conclusions Our results show that in vivo, MxA is able per se to reduce HBV expression by a post-transcriptional mechanism, and thus participates in the antiviral activity of IFN-α against HBV