Enterovirus infection and type 1 diabetes: unraveling the crime scene

Abstract

Summary Enteroviruses (EV) have been historically associated to type 1 diabetes. Definitive proof for their implication in disease development is lacking, but growing evidence suggests that they could be involved in beta cell destruction either directly by killing beta cells or indirectly by creating an exacerbated inflammatory response in the islets, capable of attracting autoreactive T cells to the ‘scene of the crime’. Epidemiological and serological studies have been associated with the appearance of islet autoimmunity and EV RNA has been detected in prospective studies. In addition, the EV capsid protein has been detected in the islets of recent‐onset type 1 diabetic donors, suggesting the existence of a low‐grade EV infection that could become persistent. Increasing evidence in the field shows that a ‘viral signature’ exists in type 1 diabetes and involves interferon responses that could be sustained during prolonged periods. These include the up‐regulation of markers such as protein kinase R (PKR), melanoma differentiation‐associated protein 5 (MDA5), retinoic acid inducible gene I (RIG‐I), myxovirus resistance protein (MxA) and human leukocyte antigen‐I (HLA‐I) and the release of chemokines able to attract immune cells to the islets leading to insulitis. In this scenario, the hyperexpression of HLA‐I molecules would promote antigen presentation to autoreactive T cells, favoring beta cell recognition and, ultimately, destruction. In this review, an overview is provided of the standing evidence that implicates EVs in beta cell ‘murder’, the time‐line of events is investigated from EV entry in the cell to beta cell death and possible accomplices are highlighted that might be involved in beta cell demise.

Seroprevalence of group B Coxsackieviruses: Retrospective study in an Italian population

“…CVB seem also able to establish persistent infection in heart 7 and pancreatic islets, 8 and the reactivation could be linked to disease development 6 . Interestingly, CVB infection has been proposed as immunologic trigger for the development of insulin‐dependent diabetes, 9,10 although currently there are no confirmed causal evidence. In a recent study, however, a vaccine for B1 serotype conferred protection against virus‐induced type 1 diabetes in a mouse model 11 …”

Chemokines as Drivers of the Autoimmune Destruction in Type 1 Diabetes: Opportunity for Therapeutic Intervention in Consideration of an Optimal Treatment Schedule

“…Although there is still debate on how the autoimmune response against islet autoantigens is initiated, it seems clear that local inflammation in the islets participates in drawing a broad variety of leukocytes to the islet microenvironment (1). Of course, virus infection has been associated with the etiology of T1D and there is ample evidence to support this hypothesis (2). For example, enterovirus proteins and RNA have been found in islets of T1D patients (3).…”

The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins?

“…Like other diseases associated with the coronavirus family such as SARS, COVID-19 is mainly a disease of the respiratory system that could interact with the metabolic and endocrine system [13]. Enteroviruses [14], hepatitis C virus [15] and prion-like protein aggregates [16] have been suspected to play a role in the pathobiology of diabetes. Diabetics also present defects in adaptive immunity, delayed Th-1 type hypersensitive reactions and reduced lymphocyte proliferation [11,17].…”