Viruses in type 1 diabetes

Abstract

Environmental factors play an important role in the pathogenesis of type 1 diabetes and can determine if a genetically susceptible individual develops the disease. Increasing evidence suggest that among other exogenous agents certain virus infections can contribute to the beta-cell damaging process. Possible viral etiology of type 1 diabetes has been explored extensively but the final proof for causality is still lacking. Currently, the group of enteroviruses (EVs) is considered as the strongest candidate. These viruses have been found in the pancreas of type 1 diabetic patients, and epidemiological studies have shown more EV infections in diabetic patients than in controls. Prospective studies, such as the Type 1 Diabetes Prediction and Prevention (DIPP) study in Finland, are of fundamental importance in the evaluation viral effects as they can cover all stages of the beta-cell damaging process, including those preceding the initiation of the process. DIPP study has carried out the most comprehensive virological analyses ever done in prospective cohorts. This article summarizes the findings from these analyses and discuss them in the context of the existing other knowledge and the prospects for intervention studies with EV vaccines or antiviral drugs.

Autoreactive T cells in type 1 diabetes

“…Earlier studies also reported aberrant expression of HLA-II molecules by β cells in 22 of 26 and 6 of 12 pancreata from patients with recent-onset and long-standing disease, respectively (25,27,28). Expression of HLA-I/II molecules may be triggered by viruses linked to T1D (29,30). Inflammatory cytokines (IFN-γ plus TNF-α or lymphotoxin) induce HLA-I/II molecules on β cells in vitro (31,32).…”

“…Along with their epidemiological associations (29,30), enterovirus infections of β cells impair insulin secretion (118), alter mRNA/miRNA expression (119,120), and induce interferon responses (121,122) that promote β cell stress, dysfunction, and apoptosis (123). Enteroviruses may also trigger autoimmunity via presentation of self-molecules in an inflammatory context (bystander activation) (124) and/or by molecular mimicry (125)(126)(127).…”

Anti-coxsackievirus B4 (CV-B4) enhancing activity of serum associated with increased viral load and pathology in mice reinfected with CV-B4

“…4 Prospective studies confirmed the link between EV and the development of pancreas islet autoimmunity. 5 Moreover, experimental studies, in vitro and in vivo animal models, revealed that CV-B4 may be involved in the pathogenesis of T1D through several mechanisms. 2,6,7,8 It has been shown that non-neutralizing anti-CV-B4 IgG obtained from serum of patients can increase the infection of peripheral blood mononuclear cells (PBMC) with CV-B4, which results in production of IFNa and other inflammatory cytokines.…”

Coxsackievirus B Tailors the Unfolded Protein Response to Favour Viral Amplification in Pancreatic β Cells

“…Epidemiological and research findings indicate an association between enterovirus infection and the onset of autoimmunity against β cells in T1D [9]. IFIH1 encodes melanoma differentiation-associated protein 5 (MDA5), a sensor of double-stranded RNA that initiates the innate immune response against infections by RNA viruses.…”