Science and Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
Department of Geriatrics, Gyeonggi Medical Center Pocheon Hospital, 1648 Pocheon-ro Sin-eup-dong, Pocheon-si, Gyeonggi-do, 11142, Republic of Korea.
Virol J. 2024 Sep 27;21(1):228. doi: 10.1186/s12985-024-02506-8.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated diseases. The pathophysiology of COVID-19 uses the following three mechanisms: (1) inflammasome activation mechanism; (2) cGAS-STING signaling mechanism; and (3) SAMHD1 tetramerization mechanism, which leads to IFN-I production. Interactions between the host and virus govern induction, resulting in multiorgan impacts. The NLRP3 with cGAS-STING constitutes the primary immune response. The expression of SARS-CoV-2 ORF3a, NSP6, NSP7, and NSP8 blocks innate immune activation and facilitates virus replication by targeting the RIG-I/MDA5, TRIF, and cGAS-STING signaling. SAMHD1 has a target motif for CDK1 to protect virion assembly, threonine 592 to modulate a catalytically active tetramer, and antiviral IFN responses to block retroviral infection. Plastic and allosteric nucleic acid binding of SAMHD1 modulates the antiretroviral activity of SAMHD1. Therefore, inflammasome activation, cGAS-STING signaling, and SAMHD1 tetramerization explain acute kidney injury, hepatic, cardiac, neurological, and gastrointestinal injury of COVID-19. It might be necessary to effectively block the pathological courses of diverse diseases.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）可诱导免疫介导的疾病。COVID-19 的病理生理学使用以下三种机制：（1）炎性体激活机制；（2）cGAS-STING 信号机制；（3）SAMHD1 四聚化机制，导致 IFN-I 的产生。宿主与病毒之间的相互作用控制诱导，导致多器官影响。具有 cGAS-STING 的 NLRP3 构成主要免疫反应。SARS-CoV-2 ORF3a、NSP6、NSP7 和 NSP8 的表达通过靶向 RIG-I/MDA5、TRIF 和 cGAS-STING 信号来阻断先天免疫激活并促进病毒复制。SAMHD1 具有 CDK1 的靶标基序，以保护病毒体组装，苏氨酸 592 调节具有催化活性的四聚体，以及抗病毒 IFN 反应以阻断逆转录病毒感染。SAMHD1 的可塑性和别构核酸结合调节 SAMHD1 的抗逆转录病毒活性。因此，炎性体激活、cGAS-STING 信号和 SAMHD1 四聚化解释了 COVID-19 的急性肾损伤、肝、心、神经和胃肠道损伤。可能需要有效地阻断多种疾病的病理过程。
