Gong Xiao-Qian, Sun Ying-Feng, Ruan Bao-Yang, Liu Xiao-Min, Wang Qi, Yang Hai-Ming, Wang Shuai-Yong, Zhang Peng, Wang Xiu-Hui, Shan Tong-Ling, Tong Wu, Zhou Yan-Jun, Li Guo-Xin, Zheng Hao, Tong Guang-Zhi, Yu Hai
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
Tianjin Animal Husbandry and Veterinary Research Institute, Tianjin 300381,China.
Vet Microbiol. 2017 Jun;205:66-70. doi: 10.1016/j.vetmic.2017.05.004. Epub 2017 May 10.
Swine influenza viruses have been circulating in pigs throughout world and might be potential threats to human health. PA-X protein is a newly discovered protein produced from the PA gene by ribosomal frameshifting and the effects of PA-X on the 1918 H1N1, the pandemic 2009 H1N1, the highly pathogenic avian H5N1 and the avian H9N2 influenza viruses have been reported. However, the role of PA-X in the pathogenesis of swine influenza virus is still unknown. In this study, we rescued the H1N1 wild-type (WT) classical swine influenza virus (A/Swine/Guangdong/1/2011 (H1N1)) and H1N1 PA-X deficient virus containing mutations at the frameshift motif, and compared their replication properties and pathogenicity of swine influenza virus in vitro and in vivo. Our results show that the expression of PA-X inhibits virus replication and polymerase activity in cultured cells and decreases virulence in mouse models. Therefore, our study demonstrates that PA-X protein acts as a negative virulence regulator for classical H1N1 swine influenza virus and decreases virulence by inhibiting viral replication and polymerase activity, deepening our understanding of the pathogenesis of swine influenza virus.
甲型流感病毒一直在全球猪群中传播，可能对人类健康构成潜在威胁。PA-X蛋白是一种通过核糖体移码由PA基因产生的新发现蛋白，并且PA-X对1918年H1N1、2009年大流行H1N1、高致病性禽流感H5N1和禽流感H9N2流感病毒的影响已有报道。然而，PA-X在甲型流感病毒发病机制中的作用仍然未知。在本研究中，我们拯救了H1N1野生型（WT）经典甲型流感病毒（A/猪/广东/1/2011（H1N1））和在移码基序处含有突变的H1N1 PA-X缺陷病毒，并比较了它们在体外和体内的甲型流感病毒复制特性和致病性。我们的结果表明，PA-X的表达抑制培养细胞中的病毒复制和聚合酶活性，并降低小鼠模型中的毒力。因此，我们的研究表明，PA-X蛋白作为经典H1N1甲型流感病毒的负毒力调节因子，通过抑制病毒复制和聚合酶活性来降低毒力，加深了我们对甲型流感病毒发病机制的理解。
