SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex.
SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex.
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SARS冠状病毒木瓜蛋白酶样蛋白酶通过与STING-TRAF3-TBK1复合物相互作用抑制I型干扰素信号通路
DOI：
10.1007/s13238-014-0026-3
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发表时间：
2014-05
期刊：
影响因子：
21.1
通讯作者：
Chen, Zhongbin
中科院分区：
文献类型：
--
作者：
Chen, Xiaojuan;Yang, Xingxing;Zheng, Yang;Yang, Yudong;Xing, Yaling;Chen, Zhongbin
SARS冠状病毒（SARS-CoV）产生了一种拮抗机制，通过这种机制可以逃避干扰素（IFN）的抗病毒活性。先前的研究表明，SARS冠状病毒木瓜蛋白酶样蛋白酶（PLpro）抑制IRF 3途径的激活，这通常会引起强烈的IFN应答，但SARS PLpro抑制IRF 3途径激活的机制尚不完全清楚。在这项研究中，我们发现了一种新的机制，可以解释SARS PLpro如何有效地抑制IRF 3通路的激活。我们发现，SARS-CoV的膜锚定PLpro结构域（PLpro-TM）的表达抑制了STING/TBK 1/IKKε介导的I型IFN的激活，并破坏了由STING和TBK 1激活的IRF 3的磷酸化和二聚化。同时，我们发现PLpro-TM与TRAF 3、TBK 1、IKKε、STING和IRF 3物理相互作用，这些是组装STING-TRAF 3-TBK 1复合物以激活IFN表达的关键组分。然而，PLpro-TM破坏了STING-TRAF 3-TBK 1复合物中组分之间的相互作用。此外，SARS PLpro-TM降低了STING-TRAF 3-TBK 1复合物中RIG-I、STING、TRAF 3、TBK 1和IRF 3的泛素化形式的水平。这些结果共同指出了SARS-CoV使用的一种新机制，PLpro通过与STING-TRAF 3-TBK 1复合物的相互作用负调控IRF 3的激活，产生了SARS-CoV对抗宿主先天免疫的对策。
SARS coronavirus (SARS-CoV) develops an antagonistic mechanism by which to evade the antiviral activities of interferon (IFN). Previous studies suggested that SARS-CoV papain-like protease (PLpro) inhibits activation of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism(s) used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro efficiently inhibits activation of the IRF3 pathway. We found that expression of the membrane-anchored PLpro domain (PLpro-TM) from SARS-CoV inhibits STING/TBK1/IKKε-mediated activation of type I IFNs and disrupts the phosphorylation and dimerization of IRF3, which are activated by STING and TBK1. Meanwhile, we showed that PLpro-TM physically interacts with TRAF3, TBK1, IKKε, STING, and IRF3, the key components that assemble the STING-TRAF3-TBK1 complex for activation of IFN expression. However, the interaction between the components in STING-TRAF3-TBK1 complex is disrupted by PLpro-TM. Furthermore, SARS PLpro-TM reduces the levels of ubiquitinated forms of RIG-I, STING, TRAF3, TBK1, and IRF3 in the STING-TRAF3-TBK1 complex. These results collectively point to a new mechanism used by SARS-CoV through which PLpro negatively regulates IRF3 activation by interaction with STING-TRAF3-TBK1 complex, yielding a SARS-CoV countermeasure against host innate immunity.
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影响因子：
5.4
作者：
Lindner, HA;Fotouhi-Ardakani, N;Ménard, R
通讯作者：
Ménard, R
DOI：
10.1073/pnas.0603144103
发表时间：
2006-08-22
影响因子：
11.1
作者：
Kamitani, Wataru;Narayanan, Krishna;Makino, Shinji
通讯作者：
Makino, Shinji
影响因子：
16.8
作者：
Huang, Yi-He;Liu, Xiang-Yu;Su, Xiao-Dong
通讯作者：
Su, Xiao-Dong
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影响因子：
5.4
作者：
Clementz, Mark A.;Chen, Zhongbin;Baker, Susan C.
通讯作者：
Baker, Susan C.
影响因子：
4.1
作者：
Evans, PC;Ovaa, H;Smith, TS
通讯作者：
Smith, TS