Porcine circovirus type 2 inhibits inter-β expression by targeting Karyopherin alpha-3 in PK-15 cells

Virology. 2018 Jul:520:75-82. doi: 10.1016/j.virol.2018.05.008. Epub 2018 May 26.

Abstract

Interferon (IFN)-mediated antiviral response is an important part of host defense. Previous studies reported that porcine circovirus type 2 (PCV2) inhibits interferon production, but the mechanism is still poorly understood. In this study, PCV2 suppresses IFN-β and IRF3 promoters and mRNA level of IFN-β induced by ISD or Poly(I:C), but has no effect on the activation of AP-1 and NF-κB. Furthermore, PCV2 decreases the mRNA level of IFN-β and IFN-β promoter activity driven by STING, TBK1, IRF3, and IRF3/5D, and causes a reduction in the protein level of nuclear p-IRF3. In addition, PCV2 interrupts the interaction of KPNA3, rather than KPNA4, with p-IRF3. Overexpression of KPNA3 restores IFN-β promoter activity. These results indicate that PCV2 disrupts the interaction of KPNA3 with p-IRF3 and blocks p-IRF3 translocation to the nucleus, thereby inhibiting IFN-β induction in PK-15 cells.

Keywords: IRF3; Interferon; Karyopherin; Porcine circovirus type 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Circovirus / drug effects
  • Circovirus / genetics
  • Circovirus / physiology*
  • Epithelial Cells / virology
  • Host-Pathogen Interactions
  • Interferon Regulatory Factor-3 / genetics
  • Interferon-beta / genetics*
  • NF-kappa B / genetics
  • Poly I-C / pharmacology
  • Promoter Regions, Genetic
  • Signal Transduction
  • Swine
  • alpha Karyopherins / genetics
  • alpha Karyopherins / metabolism*

Substances

  • Interferon Regulatory Factor-3
  • NF-kappa B
  • alpha Karyopherins
  • Interferon-beta
  • Poly I-C