Coxsackievirus B1 is associated with induction of β-cell autoimmunity that portends type 1 diabetes

Diabetes. 2014 Feb;63(2):446-55. doi: 10.2337/db13-0619. Epub 2013 Aug 23.


The rapidly increasing incidence of type 1 diabetes implies that environmental factors are involved in the pathogenesis. Enteroviruses are among the suspected environmental triggers of the disease, and the interest in exploring the possibilities to develop vaccines against these viruses has increased. Our objective was to identify enterovirus serotypes that could be involved in the initiation of the disease process by screening neutralizing antibodies against 41 different enterovirus types in a unique longitudinal sample series from a large prospective birth-cohort study. The study participants comprised 183 case children testing persistently positive for at least two diabetes-predictive autoantibodies and 366 autoantibody-negative matched control children. Coxsackievirus B1 was associated with an increased risk of β-cell autoimmunity. This risk was strongest when infection occurred a few months before autoantibodies appeared and was attenuated by the presence of maternal antibodies against the virus. Two other coxsackieviruses, B3 and B6, were associated with a reduced risk, with an interaction pattern, suggesting immunological cross-protection against coxsackievirus B1. These results support previous observations suggesting that the group B coxsackieviruses are associated with the risk of type 1 diabetes. The clustering of the risk and protective viruses to this narrow phylogenetic lineage supports the biological plausibility of this phenomenon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / blood
  • Autoimmunity
  • Case-Control Studies
  • Cell Line
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / etiology*
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / virology
  • Enterovirus B, Human / genetics
  • Enterovirus B, Human / immunology*
  • Enterovirus Infections / complications
  • Enterovirus Infections / immunology*
  • Enterovirus Infections / virology*
  • Gene Expression Regulation / physiology
  • Genotype
  • HLA-DQ beta-Chains / genetics
  • HLA-DQ beta-Chains / metabolism
  • Humans
  • Insulin-Secreting Cells / immunology*
  • Phylogeny
  • Risk Factors


  • Autoantibodies
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen