SARS-CoV-2/COVID-19 and its relationship with NOD2 and ubiquitination

Abstract

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.

Keywords: Autoinflammatory disease; COVID-19; NOD2; SARS-CoV-2; Ubiquitination; VEXAS syndrome; Yao syndrome.

Fig. 1

Clinical phenotype and dermatopathological findings. (A) Normal ear (B) Auricular inflammation (C) Right thumb swelling (D) Lower extremity purpuric papules (E) Perivascular infiltrate with lymphocytes and extravasated erythrocytes (direct immunofluorescence staining Declaration of Competing Interest

Fig. 2

Schematic representation of the interaction between SARS-CoV2, NOD2 and ubiquitination. NOD2, Nucleotide-binding oligomerization domain-containing protein 2; IRF3, Interferon regulatory factor 3; IFN-β, Interferon beta; RIPK2, Receptor interacting protein kinase 2; NFkB1, Nuclear factor kappa B; IL-1, Interleukin 1; UBA1, Ubiquitin-like modifier activating enzyme 1; IL-8, Interleukin 8; VEXAS, Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic. .