Enteroviruses and type 1 diabetes: towards a better understanding of the relationship

Abstract

Environmental factors, especially viruses, are involved in the initiation or the acceleration of type 1 diabetes (T1D) pathogenesis. Epidemiological data strongly suggest that enteroviruses, such as coxsackievirus B4 (CV-B4), can be associated with T1D. It has been demonstrated that enterovirus infections were significantly more prevalent in at risk individuals, such as siblings of diabetic patients, when they developed anti-beta-cell autoantibodies or T1D, and in recently diagnosed diabetic patients, compared with control subjects. The isolation of CV-B4 from the pancreas of diabetic patients strengthened the hypothesis of a relationship between the virus and the disease. Studies performed in vitro and in vivo in animal models helped to discover mechanisms of the infection of pancreas and other tissues, potentially able to play a role in the pathogenesis of T1D. Interestingly, it cannot be excluded that enteroviruses behave as half-devil half-angel since experimental studies suggest that, in certain conditions, these agents would be able to protect individuals against the disease. All of the plausible mechanisms by which enterovirus may be related to T1D will be reviewed here.

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

“…Type B Coxsackievirus (CV-B) encompassing CV-B 1-6, may be responsible for a large pathological specter varying from benign acute to severe chronic diseases such as chronic myocarditis, dilated cardiomyopathy, and type 1 diabetes. 2 An association between enteroviruses, especially CV-B and type 1 diabetes (T1D) was reported. Enteroviral components have been more frequently detected in blood of T1D patients, and a meta-analysis has reported a strong association between EV detection, especially CV-B, and T1D.…”

“…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. 9,10,11,12,13,14 The role of enhancing IgG levels in the outcome of CVB4 infections and other conditions such type 1 diabetes, cannot be ignored.…”

Immunoglobulin G-dependent enhancement of the infection with Coxsackievirus B4 in a murine system

“…Type B Coxsackievirus infections are generally asymptomatic, but when symptomatic, the pathological specter varies from benign acute infection of the gastrointestinal tract to severe chronic infections such as chronic myocarditis, dilated cardiomyopathy, and type 1 diabetes. 2 Indeed epidemiological data evidenced an association between enteroviruses, especially CV-B and type 1 diabetes (T1D) in genetically predisposed individuals, and experimental studies, in vitro and in vivo in animal models, revealed several mechanisms through which CV-B infection may be involved in the pathogenesis of T1D. [2][3][4][5] Plasma, serum and IgG from CV-B4 E2 seropositive subjects have been shown to strongly increase the CV-B4 E2-induced production of IFNa by human peripheral blood mononuclear cells (PBMCs), in vitro.…”

“…2 Indeed epidemiological data evidenced an association between enteroviruses, especially CV-B and type 1 diabetes (T1D) in genetically predisposed individuals, and experimental studies, in vitro and in vivo in animal models, revealed several mechanisms through which CV-B infection may be involved in the pathogenesis of T1D. [2][3][4][5] Plasma, serum and IgG from CV-B4 E2 seropositive subjects have been shown to strongly increase the CV-B4 E2-induced production of IFNa by human peripheral blood mononuclear cells (PBMCs), in vitro. 6,7 That increase was the consequence of an enhancement of the infection of PBMC with CV-B4 E2 by non-neutralizing anti-CV-B4 E2 IgG.…”

Prevalência de Lesões de Cárie de Doentes com Diabetes Mellitus Tipo 1 Tratados com Múltiplas Administrações de Insulina e de Indivíduos sem Diabetes

“…18,19,21 No entanto, a diminuição da frequência de escovagem dentária não pode estar isoladamente associada ao desenvolvimento de lesões de cárie dentária, devido à etiologia multifatorial desta doença. 6,38,39 Apresenta, contudo, um papel preponderante na prevenção do desenvolvimento da cárie dentária e na manutenção de uma boa saúde oral.…”