Poxviruses and paramyxoviruses use a conserved mechanism of STAT1 antagonism to inhibit interferon signaling.
Poxviruses and paramyxoviruses use a conserved mechanism of STAT1 antagonism to inhibit interferon signaling.
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DOI：
10.1016/j.chom.2022.01.014
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发表时间：
2022-03-09
影响因子：
30.3
通讯作者：
Smith GL
中科院分区：
文献类型：
--
作者：
Talbot-Cooper C;Pantelejevs T;Shannon JP;Cherry CR;Au MT;Hyvönen M;Hickman HD;Smith GL
STATS诱导干扰素刺激的基因是抵抗病毒感染的关键宿主防御机制。在这里，我们报告了一种高表达的痘病毒蛋白018，通过与STAT1的SH2结构域结合来抑制干扰素诱导的信号转导，从而防止STAT1与激活的干扰素受体相关联。尽管编码了干扰素诱导信号的其他抑制物，但在小鼠中，缺失018的痘病毒突变株被减弱了。018：STAT1复合体的2.0°晶体结构揭示了018与STAT1的SH2结构域结合的磷酸酪氨酸非依赖性模式。此外，STAT1结合基序018与Nipah病毒的STAT1结合蛋白相似，后者类似于018，阻断了STAT1与干扰素受体的联系。总体而言，这些结果揭示了STAT1拮抗的保守机制，该机制独立于不同的病毒家族。痘病毒蛋白018是一种毒力因子，它能抑制干扰素诱导的信号转导，结合STAT1SH2结构域，阻断其与干扰素γ受体的结合。痘苗病毒和尼帕病毒通过研究痘病毒蛋白018的收敛进化获得了STAT1结合基序。发现一种保守的病毒策略来抑制宿主的抗病毒反应。018结合STAT1 SH2结构域以阻断其与干扰素受体的募集。STAT1结合基序018存在于不同的病毒家族中，突出了其趋同进化。
The induction of interferon (IFN)-stimulated genes by STATs is a critical host defense mechanism against virus infection. Here, we report that a highly expressed poxvirus protein, 018, inhibits IFN-induced signaling by binding to the SH2 domain of STAT1, thereby preventing the association of STAT1 with an activated IFN receptor. Despite encoding other inhibitors of IFN-induced signaling, a poxvirus mutant lacking 018 was attenuated in mice. The 2.0 Å crystal structure of the 018:STAT1 complex reveals a phosphotyrosine-independent mode of 018 binding to the SH2 domain of STAT1. Moreover, the STAT1-binding motif of 018 shows similarity to the STAT1-binding proteins from Nipah virus, which, similar to 018, block the association of STAT1 with an IFN receptor. Overall, these results uncover a conserved mechanism of STAT1 antagonism that is employed independently by distinct virus families. Poxvirus protein 018 is a virulence factor that inhibits IFN-induced signaling 018 binds the STAT1 SH2 domain to block its recruitment to the IFNγ receptor The structure of the 018:STAT1 complex reveals a pTyr-independent binding mode Vaccinia and Nipah viruses acquired a STAT1-binding motif by convergent evolution Examining the poxvirus protein 018, Talbot-Cooper et al. uncover a conserved viral strategy to inhibit host anti-viral responses. 018 binds the STAT1 SH2 domain to block its recruitment to IFN receptors. The STAT1-binding motif of 018 is present in diverse virus families, highlighting its convergent evolution.
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影响因子：
32.4
作者：
GREENLUND, AC;MORALES, MO;SCHREIBER, RD
通讯作者：
SCHREIBER, RD
病毒逃避干扰素的十种策略。
影响因子：
30.3
作者：
García-Sastre A
通讯作者：
García-Sastre A
DOI：
10.1099/vir.0.065664-0
发表时间：
2014-09
期刊：
The Journal of general virology
影响因子：
--
作者：
Maluquer de Motes C;Schiffner T;Sumner RP;Smith GL
通讯作者：
Smith GL
影响因子：
3.8
作者：
Bartlett, NW;Buttigieg, K;Smith, GL
通讯作者：
Smith, GL
影响因子：
2.9
作者：
Hauser N;Gushiken AC;Narayanan S;Kottilil S;Chua JV
通讯作者：
Chua JV