Division of Rheumatology, Allergy and Immunology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, United States of America.
Department of Dermatology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, United States of America.
Clin Immunol. 2022 May;238:109027. doi: 10.1016/j.clim.2022.109027. Epub 2022 May 2.
COVID-19 infection activates the immune system to cause autoimmune and autoinflammatory diseases. We provide a comprehensive review of the relationship between SARS-CoV-2, NOD2 and ubiquitination. COVID-19 infection partly results from host inborn errors and genetic factors and can lead to autoinflammatory disease. The interaction between defective NOD2 and viral infection may trigger NOD2-associated disease. SARS-CoV-2 can alter UBA1 and abnormal ubiquitination leading to VEXAS syndrome. Both NOD2 and ubiquitination play important roles in controlling inflammatory process. Receptor interacting protein kinase 2 is a key component of the NOD2 activation pathway and becomes ubiquitinated to recruit downstream effector proteins. NOD2 mutations result in loss of ubiquitin binding and increase ligand-stimulated NOD2 signaling. During viral infection, mutations of either NOD2 or UBA1 genes or in combination can facilitate autoinflammatory disease. COVID-19 infection can cause autoinflammatory disease. There are reciprocal interactions between SARS-CoV-2, NOD2 and ubiquitination.
COVID-19 感染激活免疫系统，导致自身免疫和自身炎症性疾病。我们全面回顾了 SARS-CoV-2、NOD2 和泛素化之间的关系。COVID-19 感染部分源于宿主先天错误和遗传因素，并可导致自身炎症性疾病。缺陷型 NOD2 与病毒感染的相互作用可能引发与 NOD2 相关的疾病。SARS-CoV-2 可改变 UBA1 和异常泛素化，导致 VEXAS 综合征。NOD2 和泛素化在控制炎症过程中都起着重要作用。受体相互作用蛋白激酶 2 是 NOD2 激活途径的关键组成部分，可被泛素化以募集下游效应蛋白。NOD2 突变导致泛素结合丧失，并增加配体刺激的 NOD2 信号。在病毒感染过程中，NOD2 或 UBA1 基因突变或联合突变均可促进自身炎症性疾病的发生。COVID-19 感染可导致自身炎症性疾病。SARS-CoV-2、NOD2 和泛素化之间存在相互作用。
