Cellular microRNA bta-miR-222 suppresses caprine parainfluenza virus type 3 replication via downregulation of interferon regulatory factor 2

Vet Microbiol. 2018 Oct:224:58-65. doi: 10.1016/j.vetmic.2018.08.028. Epub 2018 Aug 29.

Abstract

Caprine parainfluenza virus type 3 (CPIV3) is an important respiratory pathogen in the goat industry and was detected in China in 2014. Numerous studies have shown that microRNAs (miRNAs) play critical roles in viral infections, but the involvement of miRNAs during CPIV3 infection is poorly understood. In this study, we showed by deep sequencing that a panel of miRNAs, including bta-miR-222, were significantly downregulated in Madin-Darby bovine kidney (MDBK) cells infected with CPIV3 strain JS2013 compared with uninfected MDBK cells. Overexpression of bta-miR-222 significantly reduced CPIV3 replication in vitro, while inhibition of endogenous bta-miR-222 enhanced CPIV3 replication. Bta-miR-222 enhanced type I interferon expression and suppressed CPIV3 replication in MDBK cells. Moreover, we showed using luciferase reporter assays that bta-miR-222 directly targeted the 3'-untranslated region of interferon regulatory factor 2 (IRF2). Transfection of cells with bta-miR-222 mimics resulted in decreased IRF2 mRNA and protein levels, with a consequent increase in type I interferon levels and potentiation of antiviral responses. Together, these data demonstrate the important role of bta-miR-222 in restricting CPIV3 replication and suggest potential antiviral strategies against CPIV3.

Keywords: Caprine parainfluenza virus type 3; Interferon regulatory factor 2; bta-miR-222; miRNA.

MeSH terms

  • Animals
  • Cattle
  • Cell Line
  • DNA Replication
  • Down-Regulation
  • HEK293 Cells
  • Humans
  • Interferon Regulatory Factor-2 / genetics*
  • Interferon Type I / genetics
  • Kidney / cytology
  • Kidney / virology
  • MicroRNAs / genetics*
  • Parainfluenza Virus 3, Human / genetics
  • Parainfluenza Virus 3, Human / physiology*
  • Transfection
  • Virus Replication / genetics*

Substances

  • Interferon Regulatory Factor-2
  • Interferon Type I
  • MicroRNAs