Prevention or acceleration of type 1 diabetes by viruses

Ghazarian, Liana; Diana, James S.; Simoni, Yannick; Beaudoin, Lucie; Lehuen, Agnès

doi:10.1007/s00018-012-1042-1

Cited by 37 publications

(28 citation statements)

References 178 publications

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“…Together with other studies showing that EVs are more frequently observed in pancreatic islets from type 1 diabetes patients than from controls [10][11][12][13] and infect human pancreatic islets in vitro (e.g. in [10,14,15]), these observations have led to the hypothesis that EVs can play a role in the aetiology of type 1 diabetes [16][17][18][19].…”

Section: Introductionmentioning

confidence: 94%

A preclinical study on the efficacy and safety of a new vaccine against Coxsackievirus B1 reveals no risk for accelerated diabetes development in mouse models

et al. 2014

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Section: Introductionmentioning

confidence: 94%

A preclinical study on the efficacy and safety of a new vaccine against Coxsackievirus B1 reveals no risk for accelerated diabetes development in mouse models

et al. 2014

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“…cells may contribute to the development of autoimmunity in some patients with type 1 diabetes [1][2][3][4]. This is important since, if verified in a majority of cases, it may provide a means to minimise the future development of type 1 diabetes in susceptible individuals via a targeted vaccination programme.…”

Section: Introductionmentioning

confidence: 99%

Expression of the enteroviral capsid protein VP1 in the islet cells of patients with type 1 diabetes is associated with induction of protein kinase R and downregulation of Mcl-1

et al. 2012

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Aims/hypothesis Immunohistochemical staining reveals that the enteroviral capsid protein VP1 is present at higher frequency in the insulin-containing islets of patients with recent-onset type 1 diabetes than in controls. This is consistent with epidemiological evidence suggesting that enteroviral infection may contribute to the autoimmune response in type 1 diabetes. However, immunostaining of VP1 is not definitive since the antibody widely used to detect the protein (Clone 5D8/1) might also cross-react with additional proteins under some conditions. Therefore, we sought to verify that VP1 immunopositivity correlates with additional markers of viral infection. Methods Antigen immunoreactivity was examined in formalin-fixed, paraffin-embedded, pancreases from two different collections of type 1 diabetes and control cases: a historical collection from the UK and the nPOD (network of Pancreatic Organ donors with Diabetes) cohort from the USA.Results VP1 immunoreactivity was present in ∼20% of insulin-containing islets of both cohorts under stringent conditions but was absent from insulin-deficient islets. The presence of VP1 was restricted to beta cells but only a minority of these contained the antigen. The innate viral sensor, protein kinase R (PKR) was upregulated selectively in beta cells that were immunopositive for VP1. The antiapoptotic protein myeloid cell leukaemia sequence-1 (Mcl-1) was abundant in beta cells that were immunonegative for VP1 but Mcl-1 was depleted in cells containing VP1. Conclusions/interpretation The presence of immunoreactive VP1 within beta cells in type 1 diabetes is associated with a cellular phenotype consistent with the activation of antiviral response pathways and enhanced sensitivity to apoptosis. However, definitive studies confirming whether viral infections are causal to beta cell loss in human diabetes are still awaited.

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“…Epidemiological studies have suggested that infections with enteroviruses, in particular those of the coxsackie B virus (CVB) serotypes, may be linked to islet autoimmunity and development of type 1 diabetes [1][2][3][4][5]. Other observations suggesting that infections with these viruses have a causative role in diabetes development come from studies that found enteroviruses more frequently in pancreases [6][7][8] and, in some studies, also gut biopsies [9][10][11], from patients with type 1 diabetes compared with healthy controls.…”

Section: Introductionmentioning

confidence: 99%

“…Based upon the observations linking enterovirus infections to the development of type 1 diabetes [1][2][3][4][5], it would be expected that such infections are more common in countries with a high disease incidence compared with those with an intermediate or low incidence. In contrast to this assumption, epidemiological studies conducted in different geographical regions of Europe have demonstrated that the frequency of enterovirus infections in the background population shows an inverse correlation to the incidence of type 1 diabetes [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

“…This model, proposed by Viskari et al, states that a low frequency of enterovirus infections in the background population increases the risk for severe complications such as beta cell damage and type 1 diabetes in infected young individuals [22]. The heightened risk for diabetes development may be explained by lower levels and a narrower serotype-spectrum of maternally transferred antibodies, or by children being exposed to enteroviruses later in childhood when the protective effect of maternal antibodies has waned [5,[22][23][24][25]. Indirect evidence for this hypothesis has recently been published, demonstrating that high levels of maternal enterovirus antibodies in serum and breast milk correlate with a reduced frequency of such infections in children [26].…”

Section: Introductionmentioning

confidence: 99%

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Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

et al. 2013

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Aims/hypothesis Enterovirus (e.g. Coxsackie B virus serotypes [CVBs]) infections may be associated with development of type 1 diabetes. Studies conducted in several European countries have, however, shown an inverse correlation between the incidence of type 1 diabetes and the prevalence of enterovirus infections. These findings could in part be explained by an extension of the poliovirus hypothesis, suggesting that the absence of maternally transferred antibodies protecting offspring from early infection increases the risk for diabetes development. Experimental evidence supporting this hypothesis in type 1 diabetes is, however, lacking. As maternally transferred protection from infection is a crucial component of the extended poliovirus hypothesis, we here tested the hypothesis that previously infected females transfer protection against infection and diabetes to offspring.Methods The induction of CVB-specific maternal antibodies and transfer of protection from virus infection, replication and development of virus-induced diabetes to offspring was assessed using NOD and Socs1-transgenic NOD mice. Results Infected mice produced neutralising antibodies to CVB. Offspring from infected females were positive for neutralising antibodies and were strongly protected from both infection and experimental diabetes. Conclusions/interpretation Our study shows that maternally transferred antibodies protect offspring from enterovirus infection and virus-induced diabetes. This suggests that the absence of maternally provided protection increases the risk for severe outcomes after an enterovirus infection in offspring. Moreover, our findings may have implications for the design of prospective studies aimed at investigating the possible role of enterovirus infections in the aetiology of human type 1 diabetes.

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Prevention or acceleration of type 1 diabetes by viruses

Cited by 37 publications

References 178 publications

A preclinical study on the efficacy and safety of a new vaccine against Coxsackievirus B1 reveals no risk for accelerated diabetes development in mouse models

A preclinical study on the efficacy and safety of a new vaccine against Coxsackievirus B1 reveals no risk for accelerated diabetes development in mouse models

Expression of the enteroviral capsid protein VP1 in the islet cells of patients with type 1 diabetes is associated with induction of protein kinase R and downregulation of Mcl-1

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

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