MicroRNA hsa-miR-203a-3p promotes H1N1 and NDV Virus Replication by suppressing the IFNA signaling

MicroRNAs (miRNAs) are small non-coding molecules that act as essential post-transcriptional regulators in various biological processes. Many studies suggest that miRNAs may modulate the host’s immune response during virus infections. We analyzed publicly available transcriptomics data involving infection with different RNA viruses and selected the most prominent candidate, miR-203a-3p. miR-203a-3p is upregulated during H7N1, HCV, and HIV+HPV infections. Interestingly, pathway analysis of microRNA-targeted genes shows that miR-203a-3p targets the type–I interferon pathway. In this study, we report that the expression of miR-203a-3p is elevated in response to polyinosinic-polycytidylic acid [poly(I:C)] transfection and infection with RNA viruses like Newcastle Disease Virus (NDV) and H1N1 influenza virus. We found that overexpression of miR-203-3p promotes the replication of H1N1 virus by suppressing the host’s type-I interferons and interferon-stimulated genes. In addition, miR-203a-3p overexpression reduced the expression of ISGs, and is attributed to the binding of miR-203a-3p to 3’ UTRs of Janus-activated kinase 1 (JAK1), STAT1, SOCS3, and multiple IFNA transcripts, as shown by luciferase and Ago-2 pulldown assays. Altogether, these findings strongly suggest that miR-203a-3p acts as a pro-viral molecule during H1N1 and NDV infection by targeting the host’s IFN signaling pathways.