军事医学2024，Vol.48Issue(6)：453-460,8.DOI:10.7644/j.issn.1674-9960.2024.06.008
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
SARS-CoV-2 PLpro negatively regulates interferon-β immune pathway induced by DDX3
摘要
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.关键词
严重急性呼吸综合征冠状病毒2/木瓜样蛋白酶/DEAD-box解旋酶3/抗病毒天然免疫Key words
severe acute respiratory syndrome coronavirus-2/papain-like protease/DEAD-box helicase 3/antiviral innate immunity分类
生物科学引用本文复制引用
王明宇,陈晓娟,孟欢,邵丽婷,焦园园,李文倩,李萍,邢雅玲..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[J].军事医学,2024,48(6):453-460,8.基金项目
国家自然科学基金面上项目(82072285) （82072285）
