RPB5-Mediating Protein Suppresses Hepatitis B Virus (HBV) Transcription and Replication by Counteracting the Transcriptional Activation of Hepatitis B virus X Protein in HBV Replication Mouse Model

Background: RPB5-Mediating protein (RMP) is associated with the RNA polymerase II subunit RPB5. This protein functionally counteracts the transcriptional activation of Hepatitis B Virus X protein (HBx) by competitively binding to the RPB5; however, the effects of RMP on Hepatitis B virus (HBV) transcription and replication remain unknown. Objectives: The purpose of this study was to investigate the effect of RMP on viral transcription and replication in vivo by using the hydrodynamic-based HBV replication mouse model. Materials and Methods: Male balb/c mice were transfected with wild type (1.2 wt) or the HBx minus HBV plasmids (1.2x (-)) with or without HBx and RMP, to establish an HBV replication mouse model by hydrodynamic injection through the tail vein. The HBV RNA and HBV DNA replication intermediates (RI) were analyzed in the liver. Results: RPB5-Mediating protein could inhibit HBV transcription and replication in groups transfected with the 1.2 wt and HBx. The inhibitory effect disappeared in the 1.2x (-) groups, yet it reappeared in the groups co-transfected with 1.2x (-) and HBx. An inhibitory effect was indicated at a low dose of RMP (0.3 ug, 0.5 ug and 0.7 ug) compared to the control group and groups that had received high doses of RMP. Conclusions: Our study demonstrated that a low dose of RMP could inhibit HBV transcription and replication, which is dependent on the appearance of HBx in vivo.