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

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-beta and IRF3 promoters and mRNA level of IFN-beta induced by ISD or Poly(I:C), but has no effect on the activation of AP-1 and NF-kB. Furthermore, PCV2 decreases the mRNA level of IFN-beta and IFN-beta 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-beta 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-beta induction in PK-15 cells.