MicroRNA-30c Modulates Type I IFN Responses To Facilitate Porcine Reproductive and Respiratory Syndrome Virus Infection by Targeting JAK1

J Immunol. 2016 Mar 1;196(5):2272-82. doi: 10.4049/jimmunol.1502006. Epub 2016 Jan 29.

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen and has evolved several mechanisms to evade IFN-I responses. We report that a host microRNA, miR-30c, was upregulated by PRRSV via activating NF-κB and facilitated its ability to infect subject animals. Subsequently, we demonstrated that miR-30c was a potent negative regulator of IFN-I signaling by targeting JAK1, resulting in the enhancement of PRRSV infection. In addition, we found that JAK1 expression was significantly decreased by PRRSV and recovered when miR-30c inhibitor was overexpressed. Importantly, miR-30c was also upregulated by PRRSV infection in vivo, and miR-30c expression corresponded well with viral loads in lungs and porcine alveolar macrophages of PRRSV-infected pigs. Our findings identify a new strategy taken by PRRSV to escape IFN-I-mediated antiviral immune responses by engaging miR-30c and, thus, improve our understanding of its pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Gene Expression Regulation
  • Interferon Type I / metabolism*
  • Janus Kinase 1 / chemistry
  • Janus Kinase 1 / genetics*
  • Janus Kinase 1 / metabolism
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • NF-kappa B / metabolism
  • Porcine Reproductive and Respiratory Syndrome / genetics*
  • Porcine Reproductive and Respiratory Syndrome / metabolism*
  • Porcine Reproductive and Respiratory Syndrome / virology
  • Porcine respiratory and reproductive syndrome virus / physiology*
  • RNA Interference*
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Signal Transduction
  • Swine
  • Up-Regulation
  • Virus Replication

Substances

  • Interferon Type I
  • MicroRNAs
  • NF-kappa B
  • RNA, Messenger
  • Janus Kinase 1