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SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex.
Protein Cell. 2014 May; 5(5):369-81.PC

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/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.

Authors+Show Affiliations

Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24622840

Citation

Chen, Xiaojuan, et al. "SARS Coronavirus Papain-like Protease Inhibits the Type I Interferon Signaling Pathway Through Interaction With the STING-TRAF3-TBK1 Complex." Protein & Cell, vol. 5, no. 5, 2014, pp. 369-81.
Chen X, Yang X, Zheng Y, et al. SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex. Protein Cell. 2014;5(5):369-81.
Chen, X., Yang, X., Zheng, Y., Yang, Y., Xing, Y., & Chen, Z. (2014). SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex. Protein & Cell, 5(5), 369-81. https://doi.org/10.1007/s13238-014-0026-3
Chen X, et al. SARS Coronavirus Papain-like Protease Inhibits the Type I Interferon Signaling Pathway Through Interaction With the STING-TRAF3-TBK1 Complex. Protein Cell. 2014;5(5):369-81. PubMed PMID: 24622840.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex. AU - Chen,Xiaojuan, AU - Yang,Xingxing, AU - Zheng,Yang, AU - Yang,Yudong, AU - Xing,Yaling, AU - Chen,Zhongbin, Y1 - 2014/03/14/ PY - 2013/12/11/received PY - 2014/01/13/accepted PY - 2014/3/14/entrez PY - 2014/3/14/pubmed PY - 2014/12/15/medline SP - 369 EP - 81 JF - Protein & cell JO - Protein Cell VL - 5 IS - 5 N2 - 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. SN - 1674-8018 UR - https://www.unboundmedicine.com/medline/citation/24622840/SARS_coronavirus_papain_like_protease_inhibits_the_type_I_interferon_signaling_pathway_through_interaction_with_the_STING_TRAF3_TBK1_complex_ L2 - https://dx.doi.org/10.1007/s13238-014-0026-3 DB - PRIME DP - Unbound Medicine ER -