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.
Innate Immune Response Induced by Severe Fever with Thrombocytopenia Syndrome Virus and Its Regulatory Mechanism by Ubiquitination Modification
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.
Severe fever with thrombocytopenia syndrome virusInnate immunityIFN signaling pathwayUbiquitinationDeubiquitination
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