SARS-CoV-2感染激活肺干扰素基因通路环鸟苷-腺苷-单磷酸合成酶刺激因子研究进展

G. Aragão, S. G. Feitosa, H. Veras, Cícero Gilmário A. P. de Lima Filho, Karinne da S. Assunção, Luana M. Arrais, Sara Lívia M. Teixeira
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引用次数: 0

摘要

COVID-19的感染与肺上皮细胞的破坏直接相关,而环鸟苷单磷酸腺苷单磷酸合成酶干扰素基因刺激因子(cGAS-STING)系统与呼吸道感染的病理有关。本研究旨在系统梳理COVID-19病理生理与肺部cGAS-STING系统激活之间的关系。严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)是一种属于冠状病毒科的RNA病毒,其遗传物质由单个阳性RNA分子(RNA+)产生。cGAS-STING信号通路已成为感染和细胞或组织应激引起的损伤的关键介质。cGAS-STING循环通路是先天免疫的一部分,在新形成的合胞体中,通过细胞间融合,以血管紧张素转换酶2 (ACE2)表达和SARS-CoV-2刺突蛋白为目标,在胞质DNA反应中被激活。虽然这一途径通常被认为对病原体来源和宿主来源的DNA都有反应,但它已被证明与视黄酸诱导基因I (RIG-I)样受体(rlr)交叉交流。在SARS-CoV-2感染情况下,cGAS-STING激活对干扰素(主要是i型干扰素(IFN-I))的产生具有重要意义,这表明cGAS-STING途径具有重要的抗病毒作用。研究发现,在SARS-CoV-2中,cGAS-STING轴被激活,但炎症反应可能针对感染细胞中的核因子-κB (NF-κB),并且该轴被免疫系统细胞产生的细胞因子风暴增强。
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SARS-CoV-2 infection activates the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes pathway in the lung: a review
The infection of COVID-19 is directly linked to the destruction of lung epithelial cells, and the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) system has been implicated in the pathology of respiratory infections. This study aimed to systematize the relationship between the pathophysiology of COVID-19 and the cGAS-STING system’s activation in the lungs. Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is an RNA virus that belongs to the Coronaviridae family whose genetic material is produced by a single positive RNA molecule (RNA+). The cGAS-STING signaling pathway has emerged as a key mediator of injury caused by infection and cellular or tissue stress. The cGAS-STING cyclic pathway is part of innate immunity and is activated from cytosolic DNA responses present in newly formed syncytia, by cell-to-cell fusion, in target of angiotensin-converting enzyme 2 (ACE2) expression and SARS-CoV-2 Spike protein. Although this pathway is canonically understood to be responsive to both pathogen-derived and host-derived DNA, it has been demonstrated to cross-communicate with the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs). cGAS-STING activation is significant to interferon production, mainly type-I interferons (IFN-I), in a SARS-CoV-2 infection scenario, indicating a major antiviral role of the cGAS-STING pathway. It was identified that in SARS-CoV-2 the cGAS-STING axis is activated, but the inflammatory response could be specific for nuclear factor-κB (NF-κB) in infected cells, and that this axis is potentiated by a cytokine storm produced by the immune system’s cells.
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