Porcine circovirus type 2 inhibits inter-β expression by targeting Karyopherin alpha-3 in PK-15 cells
Porcine circovirus type 2 inhibits inter-β expression by targeting Karyopherin alpha-3 in PK-15 cells
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DOI：
10.1016/j.virol.2018.05.008
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发表时间：
2018-07-01
期刊：
影响因子：
3.7
通讯作者：
Lv, Yingjun
中科院分区：
文献类型：
--
作者：
Li, Jiansheng;Lu, Mingqing;Lv, Yingjun
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，但其机制仍知之甚少。在本研究中，PCV2 抑制 ISD 或 Poly(I:C) 诱导的 IFN-β 和 IRF3 启动子以及 IFN-β mRNA 水平，但对 AP-1 和 NF-kB 的激活没有影响。此外，PCV2 降低由 STING、TBK1、IRF3 和 IRF3/5D 驱动的 IFN-β mRNA 水平和 IFN-β 启动子活性，并导致核 p-IRF3 蛋白水平降低。此外，PCV2 中断 KPNA3（而不是 KPNA4）与 p-IRF3 的相互作用。 KPNA3 的过度表达可恢复 IFN-β 启动子活性。这些结果表明PCV2破坏KPNA3与p-IRF3的相互作用并阻断p-IRF3易位至细胞核，从而抑制PK-15细胞中IFN-β的诱导。
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.