JVI：揭示一种重要的流感病毒致病机理

cao1976

原贴由tjzhjy 发表于 2010-11-23 22:25 11月3日，国际著名病毒学期刊Journal of Virology在线发表上海巴斯德所孙兵研究组与德国Marburg大学著名病毒学家Hans-D Klenk教授及上海交通大学程金科教授合作研究的最新成果，该成果揭示了流感病毒蛋白通过利用宿主的转录后修饰系统从而促进病毒早期复制的致病机理。

近年来，几次流感病毒的大流行造成了世界范围内的恐慌和损失，深入揭示流感病毒的致病机理对抗病毒药物和疫苗研究有重要意义。流感病毒中的蛋白NS1对毒力有重要决定作用，上海巴斯德所分子病毒学研究组研究人员通过对蛋白NS1的研究发现，该蛋白在病毒感染过程中可以利用人细胞的SUMO (small ubiquitin-like modifier) 化修饰系统将自身进行SUMO化修饰。SUMO化修饰的NS1蛋白通过增强该蛋白的稳定性，从而增强了其所具备的多种有利于病毒复制的功能，促进了病毒的早期生长。更为重要的是，研究人员通过比较多种人源、禽源流感病毒后发现，这种修饰作用几乎普遍存在，但是2009年爆发的甲型H1N1流感病毒的NS1蛋白却由于蛋白长度和结构的改变不能被SUMO化修饰。这些发现揭示了一种重要的流感病毒致病机理，即NS1蛋白影响病毒生长周期，为深入了解流感病毒在宿主内的致病机理和新的抗病毒药物研发提供了新的思路和方向。


J. Virol. doi:10.1128/JVI.00877-10

SUMO1 modification of the non-structural protein 1 of influenza A virus
Ke Xu, Christoph Klenk, Bin Liu, Bjoern Keiner, Jinke Cheng, Bo-Jian Zheng, Li Li, Qinglin Han, Chen Wang, Tianxian Li, Ze Chen, Yuelong Shu, Jinhua Liu, Hans-Dieter Klenk*, and Bing Sun*

The non-structural protein 1 (NS1 protein) is one of the major factors for efficient infection rate and high virulence of influenza A virus. Although only consisting of approximately 230 amino acids, NS1 has the ability to interfere with several systems of the host viral defense. In the present study, we demonstrate that NS1 of the highly pathogenic avian influenza A/Duck/Hubei/L-1/2004(H5N1) virus interacts with human Ubc9 which is the E2-conjugating enzyme for SUMOylation, and we show that SUMO1 is conjugated to H5N1 NS1 both in transfected and infected cells. Furthermore, two lysine residues in the C-terminus of NS1 were identified as SUMO1 acceptor sites. When the SUMO1 acceptor sites were removed by mutation, NS1 underwent rapid degradation. Studies on different influenza A virus strains of human and avian origin showed that the majority of viruses possess a NS1 protein that is modified by SUMO1, except for the recently emerged swine-origin influenza A virus (S-OIV) H1N1. Interestingly, growth of SUMOylation-deficient WSN virus was retarded when compared to wild type virus. Together, these results indicate that SUMOylation enhances NS1 stability and thus promotes rapid growth of influenza A virus.