SARS-CoV-2 PLpro negatively regulates interferon-β immune pathway induced by DDX3
10.7644/j.issn.1674-9960.2024.06.008
- VernacularTitle:新型冠状病毒PLpro负调控DDX3诱导的β干扰素抗病毒免疫通路
- Author:
Mingyu WANG
1
;
Xiaojuan CHEN
;
Huan MENG
;
Liting SHAO
;
Yuanyuan JIAO
;
Wenqian LI
;
Ping LI
;
Yaling XING
Author Information
1. 军事科学院军事医学研究院生物信息中心,北京 100850
- Keywords:
severe acute respiratory syndrome coronavirus-2;
papain-like protease;
DEAD-box helicase 3;
antiviral innate immunity
- From:
Military Medical Sciences
2024;48(6):453-460
- CountryChina
- Language:Chinese
-
Abstract:
Objective To discover the host factor interacting with severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)papain-like protease(PLpro)and explore the potential mechanism.Methods The second-generation proximity-dependent biotin identification(BioID2)approach combined with mass spectrometry analysis was used to search for the potential host factors.Immunofluorescence and co-immunoprecipitation(Co-IP)assay were used to verify the interactions between DEAD-box helicase 3(DDX3)and PLpro.The influence of PLpro on DDX3-inhibitor of kappa B kinase ε(IKKε)-TANK-binding kinase 1(TBK1)and DDX3-mitochondrial antiviral signaling protein(MAVS)complexes was also investigated by Co-IP.The effect of PLpro on interferon-β(IFN-β)immune pathway and the protease activity on substrates were studied via luciferase activity assay.Results DDX3 could co-locate and interact with PLpro intracellularly.PLpro might possibly inhibit both the formation of DDX3-MAVS complex and the interactions between DDX3-IKK-ε-TBK1.PLpro could negatively regulate type Ⅰ interferon pathway.Overexpression of DDX3 could lead to a significant increase in the cleavage activity of PLpro/PLP-TM that might be significantly decreased in case of inventions with DDX3 expressions.Conclusion DDX3 may be one of the host factors that interact with SARS-CoV-2 PLpro.PLpro negatively regulates IFN-β immune pathway induced by DDX3,which may provide a favorable immune environment for virus replication.
