Li Chuntian, Zhu Zixiang, Du Xiaoli, Cao Weijun, Yang Fan, Zhang Xiangle, Feng Huanhuan, Li Dan, Zhang Keshan, Liu Xiangtao, Zheng Haixue
State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, PR China.
State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, PR China.
Virology. 2017 Sep;509:222-231. doi: 10.1016/j.virol.2017.06.023. Epub 2017 Jun 26.
The interferon-induced double-strand RNA activated protein kinase (PKR) plays important roles in host defense against viral infection. Here we demonstrate the significant antiviral role of PKR against foot-and-mouth disease virus (FMDV) and report that FMDV infection inhibits PKR expression and activation in porcine kidney (PK-15) cells. The viral nonstructural protein 3C proteinase (3C) is identified to be responsible for this inhibition. However, it is independent of the well-known proteinase activity of 3C or 3C-induced shutoff of host protein synthesis. We show that 3C induces PKR degradation by lysosomal pathway and no interaction is determined between 3C and PKR. Together, our results indicate that PKR acts an important antiviral factor during FMDV infection, and FMDV has evolved a strategy to overcome PKR-mediated antiviral role by downregulation of PKR protein.
干扰素诱导的双链RNA激活蛋白激酶（PKR）在宿主抵御病毒感染中发挥重要作用。在此，我们证明了PKR针对口蹄疫病毒（FMDV）具有显著的抗病毒作用，并报告FMDV感染会抑制猪肾（PK - 15）细胞中PKR的表达与激活。已确定病毒非结构蛋白3C蛋白酶（3C）是造成这种抑制的原因。然而，这一作用独立于3C众所周知的蛋白酶活性或3C诱导的宿主蛋白合成关闭。我们发现3C通过溶酶体途径诱导PKR降解，且未确定3C与PKR之间存在相互作用。总之，我们的结果表明PKR在FMDV感染期间是一种重要的抗病毒因子，并且FMDV已经进化出一种策略，通过下调PKR蛋白来克服PKR介导的抗病毒作用。
