Xu Guanlong, Zhang Xuxiao, Liu Qinfang, Bing Guoxia, Hu Zhe, Sun Honglei, Xiong Xin, Jiang Ming, He Qiming, Wang Yu, Pu Juan, Guo Xin, Yang Hanchun, Liu Jinhua, Sun Yipeng
Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China; China Institute of Veterinary Drug Control, Beijing, China.
Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
Virology. 2017 Aug;508:45-53. doi: 10.1016/j.virol.2017.05.002. Epub 2017 May 8.
Previous studies have identified a functional role of PA-X for influenza viruses in mice and avian species; however, its role in swine remains unknown. Toward this, we constructed PA-X deficient virus (Sw-FS) in the background of a Triple-reassortment (TR) H1N2 swine influenza virus (SIV) to assess the impact of PA-X in viral virulence in pigs. Expression of PA-X in TR H1N2 SIV enhanced viral replication and host protein synthesis shutoff, and inhibited the mRNA levels of type I IFNs and proinflammatory cytokines in porcine cells. A delay of proinflammatory responses was observed in lungs of pigs infected by wild type SIV (Sw-WT) compared to Sw-FS. Furthermore, Sw-WT virus replicated and transmitted more efficiently than Sw-FS in pigs. These results highlight the importance of PA-X in the moderation of virulence and immune responses of TR SIV in swine, which indicated that PA-X is a pro-virulence factor in TR SIV in pigs.
先前的研究已经确定了PA-X对小鼠和禽类流感病毒的功能作用；然而，它在猪身上的作用仍然未知。为此，我们在三重重配（TR）H1N2猪流感病毒（SIV）的背景下构建了PA-X缺陷病毒（Sw-FS），以评估PA-X对猪病毒毒力的影响。TR H1N2 SIV中PA-X的表达增强了病毒复制和宿主蛋白合成的关闭，并抑制了猪细胞中I型干扰素和促炎细胞因子的mRNA水平。与Sw-FS相比，在感染野生型SIV（Sw-WT）的猪的肺中观察到促炎反应延迟。此外，Sw-WT病毒在猪体内的复制和传播比Sw-FS更有效。这些结果突出了PA-X在调节猪TR SIV毒力和免疫反应中的重要性，这表明PA-X是猪TR SIV中的一个促毒力因子。
