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Rotavirus and Type 1 Diabetes

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Diabetes and Viruses

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Abstract

A strong and temporal association exists between infections of infants and children with the major childhood gastroenteritis virus, RV, and the appearance, or exacerbation, of antibodies to the islet antigens glutamic acid decarboxylase 65 (GAD 65) and islet antigen 2 (IA-2). There is no association with thyroid autoantibodies, and islet autoantibodies do not occur prior to RV infections. Epidemics peak each winter, as do diagnoses of type 1 diabetes. The dominant, HLA-DR4-binding, CD4+ T-cell autoepitopes in GAD65 and IA2 are strongly similar to sequences in the RV surface antigen, VP7. These VP7 sequences are also CD4+ T-cell epitopes for T cells from children with islet autoimmunity. The VP7-similar GAD65 and IA2 epitopes sequences also contain CD8 T-cell epitopes which are dominant at the onset of clinical type 1 diabetes, suggesting that molecular mimicry between RV sequences and islet antigens could lead to type 1 diabetes. T cells important in diabetes in NOD mice bear the gut-associated alpha4beta7 integrin, while RV becomes infectious in the duodenum by the action of pancreatic trypsin. The fact that RV can infect pancreatic beta cells in vitro and can accelerate the onset of diabetes in NOD mice with islet inflammation strengthens the case for the involvement of RV in the initiation of islet autoimmunity and type 1 diabetes.

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Authors and Affiliations

  1. Burnet Clinical Research Unit, Walter and Eliza Hall Institute of Medical Research, Melbourne Area, Australia

    Margo C. Honeyman M.Sc. Syd, Ph.D. UNSW (Director) & Leonard C. Harrison MB, BS UNSW, M.D. Melb, D.Sc. Melb, FRACP, FRCPA (Director)

Authors
  1. Margo C. Honeyman M.Sc. Syd, Ph.D. UNSW
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  2. Leonard C. Harrison MB, BS UNSW, M.D. Melb, D.Sc. Melb, FRACP, FRCPA
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Correspondence to Leonard C. Harrison MB, BS UNSW, M.D. Melb, D.Sc. Melb, FRACP, FRCPA .

Editor information

Editors and Affiliations

  1. Queen Mary's School of Medicine and Dent, Centre for Diabetes & Metabolic Medicine, Institute of Cell & Molecular Science, n/a, London, E1 2AT, United Kingdom

    Keith Taylor

  2. Tampere University Hospital, Department of Virology, University of Tampere, n/a, Tampere, 33520, Finland

    Heikki Hyöty

  3. University of Insubria & Ospedale di Cir, Varese, Italy

    Antonio Toniolo

  4. University College London Medical School, n/a, London, NW3 2PF, United Kingdom

    Arie J. Zuckerman

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Honeyman, M.C., Harrison, L.C. (2013). Rotavirus and Type 1 Diabetes. In: Taylor, K., Hyöty, H., Toniolo, A., Zuckerman, A. (eds) Diabetes and Viruses. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4051-2_18

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