Bta-miR-146b promotes infectious bovine rhinotracheitis virus replication and inhibits type I interferon expression via targeting IRAK1.

Abstract

BACKGROUND: Infectious bovine rhinotracheitis virus (IBRV) is a primary pathogen causing bovine respiratory disease syndrome. This virus can cause rhinotracheitis and vaginitis in cattle, resulting in high mortality and posing a serious threat to bovine production. MicroRNAs (miRNAs), a class of regulatory non-coding small RNAs, can modulate viral replication by influencing host immune responses. However, reports on the association between host miRNAs and IBRV infection are limited. METHODS: In this study, we screened differentially expressed miRNAs in MDBK cells after IBRV infection and determined that the expression of bta-miR-146b was significantly increased. We investigated the effects of bta-miR-146b on IBRV replication and its underlying molecular mechanisms using molecular biological techniques such as luciferase activity assays, Western Blot, and qRT-PCR, together with bioinformatics approaches. RESULTS: We found that bta-miR-146b expression was up-regulated in IBRV-infected MDBK cells. Furthermore, transfection with bta-miR-146b mimics promoted IBRV replication in MDBK cells, whereas transfection with bta-miR-146b inhibitors inhibited IBRV replication, indicating that bta-miR-146b is a pro-infection factor. Additional studies showed that bta-miR-146b mimics inhibited type I interferon expression in MDBK cells, whereas its inhibitors enhanced it. Moreover, we identified IRAK1 as a direct target of bta-miR-146b and found that silencing IRAK1 expression rescued the effects of bta-miR-146b on viral replication and type I interferon expression. CONCLUSION: These results suggest that bta-miR-146b regulates type I interferon expression and IBRV replication in MDBK cells by targeting IRAK1, and plays a key role in IBRV infection.