Enterovirus Infection and Type 1 Diabetes: Closing in on a Link?

Rodríguez-Calvo, Teresa; Herrath, Matthias G. von

doi:10.2337/db14-1931

Cited by 30 publications

(21 citation statements)

References 19 publications

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“…However, IFN-III production and responses have only recently been investigated in the context of T1D [22,23]. In addition to significant evidence supporting the importance of IFN responses to T1D pathogenesis, substantial epidemiological and biochemical evidence suggests enteroviral infections as initiators of an innate response that devolves into a β cell-specific autoimmune response [24,25]. As the enteroviral life cycle contains a dsRNA intermediate and IFIH1 is known to mediate the IFN response to dsRNA, an understanding of interactions between enteroviral infection and melanoma differentiation-associated protein 5 (MDA5) and IFN-I/III responses is critical to progressing toward a cure for this devastating disease.…”

Section: Introductionmentioning

confidence: 98%

Effects of Type 1 Diabetes-Associated IFIH1 Polymorphisms on MDA5 Function and Expression

et al. 2015

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Recent evidence has highlighted the role of the innate immune system in type 1 diabetes (T1D) pathogenesis. Specifically, aberrant activation of the interferon response prior to seroconversion of T1D-associated autoantibodies supports a role for the interferon response as a precipitating event toward activation of autoimmunity. Melanoma differentiation-associated protein 5 (MDA5), encoded by IFIH1, mediates the innate immune system's interferon response to certain viral species that form double-stranded RNA (dsRNA), the MDA5 ligand, during their life cycle. Extensive research has associated single nucleotide polymorphisms (SNPs) within the coding region of IFIH1 with T1D. This review discusses the different risk and protective IFIH1 alleles in the context of recent structural and functional analysis that relate to MDA5 regulation of interferon responses. These studies have provided a functional hypothesis for IFIH1 T1D-associated SNPs' effects on MDA5-mediated interferon responses as well as supporting the genome-wide association (GWA) studies that first associated IFIH1 with T1D.

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Section: Introductionmentioning

confidence: 98%

Effects of Type 1 Diabetes-Associated IFIH1 Polymorphisms on MDA5 Function and Expression

et al. 2015

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“…Several hypotheses have been proposed to explain why the viral genome has proven so difficult to detect in the islets of patients with T1D [1]: (i) viral infection could act as an initial trigger to activate autoimmunity but the infection may not sustain for long periods; one or multiple viruses can act in concert or in waves leading slowly to β-cell failure. (ii) The virus genome may be modified such that it becomes persistent with very low copy numbers present in infected cells being then difficult to detect [1].…”

Section: Discussionmentioning

confidence: 99%

“…Environmental factors [1], together with genetic predisposition [2], interact cooperatively to initiate chronic islet autoimmunity [3]. …”

Section: Introductionmentioning

confidence: 99%

Detection and localization of viral infection in the pancreas of patients with type 1 diabetes using short fluorescently-labelled oligonucleotide probes

et al. 2017

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Enteroviruses, specifically of the Coxsackie B virus family, have been implicated in triggering islet autoimmunity and type 1 diabetes, but their presence in pancreata of patients with diabetes has not been fully confirmed.To detect the presence of very low copies of the virus genome in tissue samples from T1D patients, we designed a panel of fluorescently labeled oligonucleotide probes, each of 17-22 nucleotides in length with a unique sequence to specifically bind to the enteroviral genome of the picornaviridae family.With these probes enteroviral RNA was detected with high sensitivity and specificity in infected cells and tissues, including in FFPE pancreas sections from patients with T1D. Detection was not impeded by variations in sample processing and storage thereby overcoming the potential limitations of fragmented RNA. Co-staining of small RNA probes in parallel with classical immunstaining enabled virus detection in a cell-specific manner and more sensitively than by viral protein.

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“…Most particularly, enteroviruses have been associated with T1D in many instances, but this still raises questions (7)(8)(9)(10)(11). However, a meta-analysis based on molecular studies showed a significant association between enteroviral infection and T1D (12).…”

Section: Introductionmentioning

confidence: 99%

An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes

Levet¹,

Médina²,

Joanou³

et al. 2017

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Enterovirus Infection and Type 1 Diabetes: Closing in on a Link?

Cited by 30 publications

References 19 publications

Effects of Type 1 Diabetes-Associated IFIH1 Polymorphisms on MDA5 Function and Expression

Effects of Type 1 Diabetes-Associated IFIH1 Polymorphisms on MDA5 Function and Expression

Detection and localization of viral infection in the pancreas of patients with type 1 diabetes using short fluorescently-labelled oligonucleotide probes

An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes

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