Host miR-146a promotes replication of human cytomegalovirus by suppressing type I IFN response in MRC-5 cells

Human cytomegalovirus (HCMV) is major cause of birth defects upon congenital infection as well as morbidity in immunosuppressed populations and has evolved several mechanisms to evade IFN-I responses. MiR-146a is found to regulate responses IFN-I in a variety of viral infections, but it is not clear whether the same function in HCMV. In this study, we study the effect of miR-146a on HCMV replication by miR-146a inhibitor and mimics. In addition, we used bioinformatics methods to find potential target genes of miR-146a. Effects of miR-146a on the immune response of type I interferon were also detected. Finally, regulation of miR-146a on the downstream IFNstimulated genes (ISGs) including ISG15, ISG56, OAS1, and Mx1 in MRC-5 cells was detected by qRT-PCR analysis. We found that a host microRNA, miR-146a, was upregulated in HCMV infected cells, which obviously facilitated HCMV replication in host cells. Subsequently, we demonstrated that miR-146a was a potent negative regulator of IFN-I signaling pathway by targeting STAT1, resulting in the enhancement of HCMV infection. The last we found that miR-146a and ISGs expression levels were negatively correlated. In conclusion, these findings indicate that miR146a suppression Type I IFN responses to human cytomegalovirus (HCMV) by targeting STAT1 in MRC-5 cells. These findings suggest that miR-146a may provide a potential strategy for anti-HCMV therapies.