Swine NONO promotes IRF3-mediated antiviral immune response by Detecting PRRSV N protein

Dandan Jiang, Chao Sui, Xiangju Wu, Ping Jiang, Juan Bai, Yue Hu, Xiaoyan Cong, Juntong Li, Dongwan Yoo, Laura C. Miller, Changhee Lee, Yijun Du, Jing Qi

Research output: Contribution to journalArticlepeer-review

Abstract

Non-POU domain-containing octamer-binding protein (NONO) is a multi-functional nuclear protein which belongs to the Drosophila behavior/human splicing (DBHS) protein family. NONO is known to regulate multiple important biological processes including host antiviral immune response. However, whether NONO can inhibit porcine reproductive and respiratory syndrome virus (PRRSV) replication is less well understood. In this study, we demonstrated that swine NONO (sNONO) inhibited PRRSV replication, via increasing expression of IFN-β, whereas NONO knockdown or knockout in PAM-KNU cells was more susceptible to PRRSV infection. As an IRF3 positive regulation factor, NONO promoted IFN-β expression by enhancing activation of IRF3. During PRRSV infection, NONO further up-regulated IRF3-mediated IFN-β expression by interacting with PRRSV N protein. Mechanistically, NONO functioned as a scaffold protein to detect PRRSV N protein and formed N-NONOIRF3 complex in the nucleus. Interestingly, it was found that the NONO protein reversed the inhibitory effect of PRRSV N protein on type I IFN signaling pathway. Taken together, our study provides a novel mechanism for NONO to increase the IRF3-mediated IFN-β activation by interacting with the viral N protein to inhibit PRRSV infection.

Original languageEnglish (US)
Article numbere1012622
JournalPLoS pathogens
Volume20
Issue number10
DOIs
StatePublished - Oct 2024

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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