Emerging Roles of Coronavirus in Autoimmune Diseases

Abstract

Virus infection can alter immune regulatory activity, and thus may be involved in the occurrence of autoimmune diseases. Recently, the pandemic of COVID-19 has posed a huge threat to public health and emerging evidence suggests that coronavirus may be implicated in the development and pathogenesis of autoimmune diseases. However, how coronavirus infection impacts the risk of autoimmune disease remains largely unknown. In this review, we focused on the association between coronavirus and autoimmunity, and elucidated the molecular mechanisms linking coronavirus exposure to autoimmunity. Additionally, we briefly introduced the role that coronavirus plays in several autoimmune diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and idiopathicthrombocytopenic purpura (ITP).

Keywords: COVID-19; Coronavirus, Autoimmune disease, Autoimmunity.

Figure 1

Immune Effects of Coronavirus Structural Proteins S protein and M protein are two important structural proteins of coronavirus, which cause a variety of immune responses. S protein can cause the increase of IL-8 level through the following two ways: a) S protein is composed of S1 and S2. The former subunit can bind to Toll-like receptor 2, activate NF-κB, and increase the level of IL-8 mRNA. b) Coronavirus causes an increase in IL-8 in PBMC and THP-1 cells. These reactions can also be induced in vitro. M protein prevents the formation of TRAF3•TANK•TBK1/IKKϵ complex which leads to the activation of IRF3 and IRF7. Therefore, the level of type 1 interferon decreases in M protein infected cells. IL-8, interleukin-8; NF-κB, nuclear factor κ-B; PBMC, peripheral blood mononuclear cell; IRF, interferon regulatory factor; IKK, IκB kinase; TRAF, tumor necrosis factor receptor-associated factor; TANK, TRAF-associated NFκB activator; TBK1, TANK binding kinase.

Figure 2

Molecular mechanisms linking coronavirus exposure and autoimmunity. There are several molecular mechanisms that explain the link between coronavirus and autoimmunity. Frist, molecular mimicry can active cross-reactive T cells because viral antigens mimic host antigens. Second, coronavirus infection can result in local pulmonary inflammation. Hyper innate inflammatory response can accumulate alveolar macrophages, stimulate PMN to secrete the myeloperoxidase and elastase, which is accompanied with increased MCP-1 and IL-8, eventually lead to pulmonary destruction. Third, the production of inflammatory cytokines activate B cells, resulting autoimmunity destruction by autoantibodies. And IFN-γ activates autoreactive T cell, NK cell and stimulates cytotoxic lymphocyte, causing the oxidative tissue injury and demyelination by macrophages/microglia. IL-8, interleukin-8; CK, cytokines; CTL, cytotoxic lymphocyte; MCP-1, monocyte chemotactic protein 1; IFN-γ, interferon-γ.

Figure 3

Potential relationship between multiple sclerosis and coronavirus infections. There is some evidence to reveal the relationship between multiple sclerosis and coronavirus infections. a) The neurotropic strains of the coronavirus mouse hepatitis virus (JHMV) can serve as a recognized mouse models for MS. It is the interaction between T cells, macrophages and microglia that lead to MS pathology featured by axonal damage and demyelination. With the long-term infection of the HMV, myelin-reactive T cells can be active by myelin debris. These cells participate in chronic inflammation by releasing cytokines. b) Previous research has detected polyadenylated RNA sequences of HCV-OC43. c) HCV-229E Positivity were also observed in multiple sclerosis cerebrospinal fluids CNS, central nervous system; MS, multiple sclerosis; CSF, cerebrospinal fluid; JHMV, mouse hepatitis virus