Essential role of hsa-miR-203a-3p in type I interferons immune homeostasis during influenza and NDV infection.

Abstract

MicroRNAs (miRNAs) are small, non-coding RNA molecules that act as essential post-transcriptional regulators in various biological processes. Many studies suggest that miRNAs may modulate the host's immune response or even viral replication during infection. We have identified hsa-miR-203a-3p as a key regulatory candidate influencing innate immune responses, based on a comprehensive analysis of publicly available transcriptomic datasets involving H7N9, HCV, or DENV2 infection. Pathway enrichment analysis of microRNA-targeted genes reveals that hsa-miR-203a-3p targets several components of type I interferon signalling and JAK-STAT pathway. In this study, we report a novel role of hsa-miR-203a-3p as it is elevated in response to polyinosinic-polycytidylic acid [poly(I:C)] transfection and infection with RNA viruses Newcastle Disease Virus (NDV) and A/PR8/H1N1 influenza virus. We found that hsa-miR-203a-3p promotes the A/PR8/H1N1 virus replication by suppressing the host's type-I interferons and interferon-stimulated genes. Our investigation demonstrated that overexpression of hsa-miR-203a-3p led to reduced expression of interferon stimulated genes (ISGs). This regulation is likely mediated through the direct binding of hsa-miR-203a-3p to the 3' UTRs of Janus-activated kinase 1 (JAK1), STAT1 and several IFN-α transcripts. Collectively, these findings highlight the pivotal role of hsa-miR-203a-3p in immune homoeostasis; it regulates type I IFN signalling and downstream antiviral responses, thereby facilitating A/PR8/H1N1 and NDV infection.