SFTSV介导的固有免疫应答及其通过抑制宿主蛋白泛素化修饰实现免疫逃逸的调控机制  

Innate Immune Response Induced by Severe Fever with Thrombocytopenia Syndrome Virus and Its Regulatory Mechanism by Ubiquitination Modification

作　　者：王佳敏 时小双 杨诗寒 金宁一 李昌 杜寿文 WANG Jiamin;SHI Xiaoshuang;YANG Shihan;JIN Ningyi;LI Chang;DU Shouwen(College of Animal Science and Veterinary Medicine,Heilongjiang Bayi Agricultural University,Daqing 163319,China;Key Laboratory of Livestock Disease Prevention of Guangdong Province,Institute of Animal Health,Guangdong Academy of Agricultural Sciences,Guangzhou 510640,China;Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses,Chinese Academy of Medical Sciences,Changchun 130122,China;State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases,Wuhan 430030,China)

机构地区：[1]黑龙江八一农垦大学动物科技学院,大庆163319 [2]广东省农业科学院动物卫生研究所,广东省畜禽疫病防治研究重点实验室,广州510640 [3]中国医学科学院人兽共患病毒病防控关键技术研究创新单元,中国农业科学院长春兽医研究所,长春130122 [4]人畜共患传染病重症诊治全国重点实验室,武汉430030

出　　处：《病毒学报》2024年第1期183-196,共14页Chinese Journal of Virology

基　　金：中国医学科学院医学与健康科技创新工程项目(项目号:2020-12M-5-001),题目:重要人兽共患病毒与宿主互作机制及新型疫苗构建研究。

摘　　要：发热伴血小板减少综合征病毒(Severe fever with thrombocytopenia syndrome virus, SFTSV)感染可造成发热伴血小板减少综合征(Severe fever with thrombocytopenia syndrome, SFTS)。SFTS重症患者大多与SFTSV引起非正常的固有固有免疫反应所导致的细胞因子风暴有关。这些早期固有固有免疫反应包括多种炎症和抗病毒基因的表达,并激活随后的固有固有免疫反应和适应性免疫。感染细胞的早期固有固有免疫反应是由模式识别受体(Pattern recognition receptors, PRRs)、接头蛋白、激酶和转录因子组成的细胞内信号通路所介导的。这些途径受复杂的翻译后修饰网络的严格调节,其中大量的泛素化酶和去泛素化酶使这些修饰可逆且高度动态。这些酶的调控作用可以增强固有免疫反应以抵抗病原体的入侵,也可以抑制其过度活化以避免病理性免疫反应。本文综述了SFTSV引起的早期固有免疫信号通路及其复杂调控机制,为后续针对SFTSV的药物开发和免疫病理学提供了基础。Severe fever with thrombocytopenia syndrome virus(SFTSV)infection causes severe fever with thrombocytopenia syndrome(SFTS).Most patients with severe SFTS are associated with cytokine storm caused by SFTSV mainly due to its abnormal innate immune response.These early innate immune responses include the expression of multiple gross inflammatory and antiviral genes that activate subsequent innate immune responses and adaptive immunity.The early innate responses of infected cells are mediated by intracellular signaling pathways consisting of pattern recognition receptors(PRRs),adapters,kinases,and transcription factors.These pathways are tightly regulated by a complex network of post‐translational modifications,which a large number of ubiquitinating and deubiquitinating enzymes make these modifications reversible and highly dynamic.The modulation of these enzymes can enhance the natural immune responses to resist pathogen invasion or inhibit their activity to avoid excessive immune responses.This paper reviews the early natural immune signaling pathways induced by SFTSV and their complex regulatory mechanisms,providing a basis for subsequent drug development and immunopathology against SFTSV.

关 键 词：新型布尼亚病毒 固有免疫 IFN-Ⅰ型信号通路 泛素化 去泛素化 

分 类 号：R373.3[医药卫生—病原生物学]