Modification of Nonstructural Protein 1 of Influenza A Virus by SUMO1
Modification of Nonstructural Protein 1 of Influenza A Virus by SUMO1
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SUMO1 对甲型流感病毒非结构蛋白 1 的修饰
DOI：
10.1128/jvi.00877-10
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发表时间：
2011-01-01
影响因子：
5.4
通讯作者：
Sun, Bing
中科院分区：
文献类型：
--
作者：
Xu, Ke;Klenk, Christoph;Sun, Bing
非结构蛋白1（NS 1）是导致甲型流感病毒高感染率和高毒力的主要因素之一。虽然只有大约230个氨基酸组成，但NS 1具有干扰宿主病毒防御的几个系统的能力。在本研究中，我们证明了高致病性禽流感A/鸭/湖北/L-1/2004（H5 N1）病毒的NS 1与人Ubc 9相互作用，Ubc 9是用于SUMO化的E2缀合酶，并且我们表明SUMO 1在转染和感染的细胞中与H5 N1 NS 1缀合。此外，在NS 1的C末端的两个赖氨酸残基被确定为SUMO 1受体位点。当SUMO 1受体位点通过突变被去除时，NS 1经历快速降解。对人类和禽类来源的不同甲型流感病毒株的研究表明，除了最近出现的猪源甲型流感病毒（S-OIV）（H1N1）外，大多数病毒都具有经SUMO 1修饰的NS 1蛋白。有趣的是，生长的sumoylation缺陷的WSN病毒突变体相比，野生型病毒的生长迟缓。总之，这些结果表明类小泛素化增强了NS 1的稳定性，从而促进了甲型流感病毒的快速生长。
ABSTRACT Nonstructural protein 1 (NS1) is one of the major factors resulting in the efficient infection rate and high level of virulence of influenza A virus. Although consisting of only 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 in both 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 of different influenza A virus strains of human and avian origin showed that the majority of viruses possess an NS1 protein that is modified by SUMO1, except for the recently emerged swine-origin influenza A virus (S-OIV) (H1N1). Interestingly, growth of a sumoylation-deficient WSN virus mutant was retarded compared to that of wild-type virus. Together, these results indicate that sumoylation enhances NS1 stability and thus promotes rapid growth of influenza A virus.