title: Enteroviral pathogenesis of type 1 diabetes: queries and answers.
abstract: OBJECTIVE
  Type 1 diabetes (T1D) results from interplay between genetic predisposition, immune system, and environmental factors. Epidemiological and experimental data strongly suggest a role for enteroviruses in the development of T1D, but a lot of controversies and unanswered questions remained. This review focuses on issues that are fueling debate.
  
  
  RESULTS
  Beyond HLA genes, which provide genetic susceptibility for T1D, other loci have been identified to be associated with the disease. There is a link between T1D and single-nucleotide polymorphisms (SNPs) in the interferon-induced helicase 1 (IFIH1) gene that encodes melanoma differentiation-associated protein 5 (MDA5). This protein is a cytoplasmic sensor for viruses especially coxsackieviruses B, the most incriminated enteroviruses in T1D pathogenesis. Upon viral infection, MDA5 stimulates the production of mediators of the innate antiviral immune response, which is believed to play a role in a 'bystander activation' scenario. Rare variants of IFIH1 through a lost or reduced expression of the protein are protective against T1D, whereas common IFIH1 SNPs are associated with the disease. However, a clear association has not been yet established between T1D-associated IFIH1 polymorphisms and enterovirus detection.
  
  
  CONCLUSIONS
  Literature have accumulated a lot of evidence supporting that enteroviruses can contribute, at least in some patients, to the pathogenesis of T1D through various mechanisms. But it is still a challenge to date to prove a causal relationship between enteroviruses and T1D. Future studies may lead to a better understanding of this relationship and ultimately can help toward disease prevention.
authors.affiliation: Université Lille 2, CHRU, Laboratoire de Virologie EA3610, Lille, France. didier.hober@chru-lille.fr
authors.forename: Didier
authors.initials: D
authors.lastname: Hober
authors.forename: Enagnon K
authors.initials: EK
authors.lastname: Alidjinou
mesh_terms: D053487:DEAD-box RNA Helicases / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000821:virology*; D004770:Enterovirus / Q000235:genetics / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000150:complications*; D020022:Genetic Predisposition to Disease; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D020641:Polymorphism, Single Nucleotide
chemical_list: C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1