Abstract
For a long time, viruses have been shown to modify the clinical picture of several autoimmune diseases, including type 1 diabetes (T1D), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren’s syndrome (SS), herpetic stromal keratitis (HSK), celiac disease (CD), and multiple sclerosis (MS). Best examples of viral infections that have been proposed to modulate the induction and development of autoimmune diseases are the infections with enteric viruses such as Coxsackie B virus (CVB) and rotavirus, as well as influenza A viruses (IAV), and herpesviruses. Other viruses that have been studied in this context include, measles, mumps, and rubella. Epidemiological studies in humans and experimental studies in animal have shown that viral infections can induce or protect from autoimmunopathologies depending on several factors including genetic background, host-elicited immune responses, type of virus strain, viral load, and the onset time of infection. Still, data delineating the clear mechanistic interaction between the virus and the immune system to induce autoreactivity are scarce. Available data indicate that viral-induced autoimmunity can be activated through multiple mechanisms including molecular mimicry, epitope spreading, bystander activation, and immortalization of infected B cells. Contrarily, the protective effects can be achieved via regulatory immune responses which lead to the suppression of autoimmune phenomena. Therefore, a better understanding of the immune-related molecular processes in virus-induced autoimmunity is warranted. Here we provide an overview of the current understanding of viral-induced autoimmunity and the mechanisms that are associated with this phenomenon.
Highlights
Autoimmune diseases (AID) develop as a result of an aberrant immune response in recognizing self and non-self-antigens
GAD65 was found to play an important role in the pathogenesis of type I diabetes as a target autoantigen [37], where the ensuing immune response to GAD65 has been detected before the onset of clinical diabetes [35]
Pane et al proposed that diabetes acceleration by rotavirus in NOD mice occur via bystander activation: Rotavirus degraded dsRNA induce Toll-like receptor 7 (TLR7) signaling, leading to release of type-I interferon and lymphocyte activation, including autoreactive T cells, which in turn exacerbate diabetes-related autoimmunity [42]
Summary
Autoimmune diseases (AID) develop as a result of an aberrant immune response in recognizing self and non-self-antigens. Viruses 2019, 11, 762 virus (HSV)-induced stromal keratitis [5], virus-induced diabetes [6], autoimmune myocarditis that is mediated by Coxsackie virus infection [7], Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) [8], and several others [9] Another hypothesized mechanism is the “bystander activation”, whereby a non-specific and an over-reactive antiviral immune response creates a localized pro-inflammatory environment along with the release of self-antigens from the damaged tissue. A related mechanism is called “epitope spreading”, in which a viral infection triggers the release of more self-antigens and the de novo activation of autoreactive cells, which spread to target additional self-epitopes [9] Both molecular mimicry and bystander activation have been observed in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) [11], West Nile virus (WNV)-mediated myasthenia gravis (MG) [12], TMEV-IDD [13], and other disorders [9]. This review summarizes the recent findings on virally induced autoimmunity and the potential underlying mechanisms triggering the development of this disorder
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call