MiR-26b Inhibits Hepatitis B Virus Transcription And Replication By Targeting Host Factors

Hepatitis B Virus (HBV) causes acute and chronic hepatitis in humans and HBV infection is one of the major threats to global health. The application of HBV vaccine prevented the diseases from spreading, but chronic hepatitis B infection is still hard to be cured currently. HBV translation and replication is regulated by a series of cellular factors in liver cells, and the virus infection can create a favorable cellular environment to increase its viral production. MicroRNAs (miRNAs) are highly conserved small noncoding RNAs participating in a variety of physiological and pathological processes. Rencently, much progress has been made in the field of the interplay between viruses and host miRNAs.In this study, we reported that overexpression of miR-26b by transfection of mimic inhibited HBV antigen expression, transcription and replication, whereas knockdown of endogenous miR-26b by its anti-sense inhibitor led to enhanced HBV production. Overexpression and knockdown experiments showed miR-26b significantly decreased HBV enhancer/promoter activities. We next identified multiple host factors including cysteine and histidine-rich domain containing1(CHORDC1) as miR-26b targets from several candidate target genes that might be involved in the regulation of HBV replication. MiR-26b markedly decreased CHORDC1protein expression via base-pairing with complementary sequences in the3’UTR of its mRNA. Overexpression and knockdown studies both showed that CHORDC1increased viral antigen expression, transcription and replication through enhancing HBV enhancer/promoter activities. We also found obviously suppressed expression of miR-26b by HBV infection in human peripheral blood mononuclear cells and liver cells. Furthermore, we found that miR-26a, another mature miRNA of hsa-miR-26family, also decreased CHORDC1expression and thus inhibited HBV production.Our results suggest that miR-26b downregulates its target genes including CHORDC1, then decreases HBV enhancer/promoter activities and therefore inhibits viral transcription, gene expression and replication in human hepatoma cells. Suppressed miR-26b expression induced by HBV infection can impact HBV replication and may contribute to viral persistence and the development of HBV related hepatocellular carcinoma (HCC).