SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex

doi:10.1007/s13238-014-0026-3

Protein Cell

2014, Vol. 5

Issue (5) : 369-381 https://doi.org/10.1007/s13238-014-0026-3 PMID: 24622840

RESEARCH ARTICLE

SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex

Xiaojuan Chen¹,Xingxing Yang^1,²,Yang Zheng¹,Yudong Yang¹,Yaling Xing¹,Zhongbin Chen^1,^2,^*(

)

1. Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing 100850, China
2. Anhui Medical University, Hefei 230032, China

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Abstract

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/IKK?-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, IKK?, 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.

Keywords SARS coronavirus papain-like protease interferon deubiquitinase STING-TRAF3-TBK1 complex

Corresponding Author(s): Zhongbin Chen

Issue Date: 25 June 2014

Cite this article:

Xiaojuan Chen,Xingxing Yang,Yang Zheng, et al. SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex[J]. Protein Cell, 2014, 5(5): 369-381.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-014-0026-3
https://academic.hep.com.cn/pac/EN/Y2014/V5/I5/369

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