Downregulation of miR-122 by porcine reproductive and respiratory syndrome virus promotes viral replication by targeting SOCS3

Vet Microbiol. 2022 Dec:275:109595. doi: 10.1016/j.vetmic.2022.109595. Epub 2022 Nov 1.

Abstract

MicroRNAs are small non-coding RNA that regulate host anti-viral immune response. In this study, we used high-throughput sequencing to identify miRNAs that were differentially expressed upon PRRSV infection in porcine alveolar macrophages. We observed that the expression level of miR-122 was decreased upon PRRSV infection. Over-expression of miR-122 remarkably suppressed PRRSV replication, while blockage of endogenous miR-122 enhanced PRRSV replication. Moreover, over-expression of miR-122 reduced the protein level of porcine suppressor of cytokine signaling 3 (SOCS3), a negative regulator of JAK-STAT signaling, resulting in enhanced production of type Ⅰ IFN. Further analysis revealed that miR-122 decreased the expression of SOCS3 at the post-transcription level by targeting the 3' UTR region of SOCS3 mRNA. In conclusion, this study demonstrates that the expression of miR-122 was reduced during PRRSV infection. miR-122 impaired PRRSV replication by promoting the production of type I interferon. Our study may provide new insights into understanding PRRSV immune evasion mechanisms.

Keywords: Interferon; MiR-122; MicroRNA; PRRSV; SOCS3.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Cell Line
  • Down-Regulation
  • Macrophages, Alveolar
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Porcine Reproductive and Respiratory Syndrome* / genetics
  • Porcine respiratory and reproductive syndrome virus* / genetics
  • Porcine respiratory and reproductive syndrome virus* / metabolism
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Swine
  • Swine Diseases* / genetics
  • Virus Replication / physiology

Substances

  • MicroRNAs
  • 3' Untranslated Regions
  • Suppressor of Cytokine Signaling Proteins