Chicken microRNA 26a-5p regulates replication of Newcastle disease virus by direct targeting of the viral polymerase

Newcastle disease (ND), caused by Newcastle disease virus (NDV), is a significant threat to the poultry industry and outbreaks of virulent strains can lead to substantial economic losses. Studies to identify molecular pathways that can be used for intervention or to reduce pathology are critical for mitigating losses due to ND. In this study, we demonstrate that chicken mir-26a-5p upregulation inhibited the replication of both lentogenic and velogenic NDV strains. Computational analysis identified a highly conserved miR-26a-5p binding site in the NDV polymerase gene and transfection of the miR-26a-5p mimic following viral infection demonstrated a direct inhibition of polymerase transcripts while inhibitor transfection led to partial rescue of the miR-26a-5p mediated repression. Alternately, stable overexpression of miR-26a-5p led to the downregulation of multiple genes in the innate immune sensing pathway and led to a small but significant increase in viral titer for a velogenic NDV strain suggesting a pro-viral role. These data identified new roles for chicken miR-26a-5p in regulating NDV replication.