猪圆环病毒 2 型通过靶向 PK-15 细胞中的核孔蛋白α-3 抑制 inter-β 的表达。
Porcine circovirus type 2 inhibits inter-β expression by targeting Karyopherin alpha-3 in PK-15 cells.
机构信息
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
出版信息
Virology. 2018 Jul;520:75-82. doi: 10.1016/j.virol.2018.05.008. Epub 2018 May 26.
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.
干扰素（IFN）介导的抗病毒反应是宿主防御的重要组成部分。先前的研究报道，猪圆环病毒 2 型（PCV2）抑制干扰素的产生，但机制尚不清楚。在本研究中，PCV2 抑制 ISD 或 Poly(I:C)诱导的 IFN-β 和 IRF3 启动子和 IFN-β mRNA 水平，但对 AP-1 和 NF-κB 的激活没有影响。此外，PCV2 降低了 STING、TBK1、IRF3 和 IRF3/5D 驱动的 IFN-β 和 IFN-β 启动子活性的 mRNA 水平，并导致核 p-IRF3 蛋白水平降低。此外，PCV2 中断了 KPNA3 而不是 KPNA4 与 p-IRF3 的相互作用。KPNA3 的过表达恢复了 IFN-β 启动子活性。这些结果表明，PCV2 破坏了 KPNA3 与 p-IRF3 的相互作用，并阻止 p-IRF3 向核内易位，从而抑制 PK-15 细胞中 IFN-β 的诱导。
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