Induction Of The Cellular MiR-29c By Influenza Virus Inhibits The Innate Immune Response

Infuenza A viruses (IAVs) are negative-sense, single-stranded, segmented RNAviruses, which primarily targets respiratory epithelial cells and produces clinicaloutcomes ranging from mild upper respiratory infection to severe pneumonia.MicroRNAs (miRNAs) represent a family of small noncoding RNAs controllingtranslation and transcription of many genes. These molecules negatively regulatesgene expression by binding completely or partially to target protein-coding mRNAs atthe posttranscriptional level for degradation or translational inhibition. Thousands ofmiRNAs have since been identified in various organisms and play essential roles ingene expression regulation of many critical cellular processes such as development,differentiation, proliferation, and hematopoiesis. The human miR-29family ofmiRNAs has three mature members, miR-29a, miR-29b, and miR-29c. Recent studieshave revealed that miR-29is involved in regulation of the innate and adaptiveimmune responses. However, the function of miR-29in the immune response to IAVinfection remains to be further explored. Our previous study has shown that miR-29family members are up-regulated during IAV infection, especially miR-29c. Here wereport that miR-29c is involved in inhibition of IAV-induced innate immune responses.We found that posttranscriptional regulation was involved in IAV-induced A20expression in A549cells. Overexpression of miR-29c with miR-29c mimic enhancedIAV-induced A20protein expression and conversely that miR-29c inhibitorsignifcantly blocked IAV-induced A20protein expression in A549cells. Furthermore,functional results showed that IAV-induced miR-29c expression correlated withdecreased NF-κ B activity and expression of several antiviral and proinfammatorycytokines via up-regμLation of A20. Together, the fndings indicate a new role ofmiR-29c in IAV infection and suggest its induction may contribute to counteract the innate immune response.