Does rotavirus turn on type 1 diabetes?

• Published in: PLoS pathogens 2019-10, Vol.15 (10), p.e1007965-e1007965
• Main Authors: Harrison, Leonard C, Perrett, Kirsten P, Jachno, Kim, Nolan, Terry M, Honeyman, Margo C
• Format: Article
• Language: English
• Subjects: Acids; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antigens; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Autoantigens; Autoimmune diseases; Biology and Life Sciences; Capsid protein; Care and treatment; CD8 antigen; Children; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - virology; Diagnosis; Disease; Epidemiology; Epitopes; Gastroenteritis; Genotype & phenotype; Genotypes; Global health; Herd immunity; Histocompatibility antigen HLA; Humans; Hyperglycemia; Immunization; Immunogenicity; Infections; Insulin; Lymphocytes; Lymphocytes T; Medical research; Medicine and Health Sciences; Mimicry; Pancreas; Pearls; Peptides; Prevalence; Proteins; Risk factors; Rotavirus; Rotavirus - pathogenicity; Rotavirus infections; Rotavirus Infections - complications; Rotavirus Infections - virology; Similarity; Surveillance; T cell receptors; Type 1 diabetes; Vaccination; Vaccines; Viruses
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1007965

About the Authors: Leonard C. Harrison * E-mail: [e-mail] Affiliation: Walter and Eliza Hall Institute for Medical Research, University of Melbourne, Melbourne, Victoria, Australia ORCID logo http://orcid.org/0000-0002-2500-8944 Kirsten P. Perrett Affiliation: Vaccine and Immunization Research Group, Murdoch Children’s Research Institute and the Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia ORCID logo http://orcid.org/0000-0002-5683-996X Kim Jachno Affiliation: Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Victoria, Australia ORCID logo http://orcid.org/0000-0003-2550-9674 Terry M. Nolan Affiliation: Vaccine and Immunization Research Group, Murdoch Children’s Research Institute and the Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia ORCID logo http://orcid.org/0000-0001-6018-3863 Margo C. Honeyman Affiliation: Walter and Eliza Hall Institute for Medical Research, University of Melbourne, Melbourne, Victoria, Australia ORCID logo http://orcid.org/0000-0002-8926-5384 Introduction Rotavirus (RV) remains the major cause of infantile gastroenteritis worldwide, although the advent of vaccination has substantially decreased associated mortality [1]. In testing the ability of peptides to stimulate blood T cells from islet autoantibody-positive T1D relatives, we identified a dominant epitope, VIVMLTPLVEDGVKQC (amino acid [aa] 805–820) in IA-2, which had 56% identity and 100% similarity over 9 aa with a sequence (aa 40–48) in the major immunogenic viral protein 7 (VP7) outer-capsid protein of human RV serotype genotype 3 (G3), strain P (Fig 1A) [6,7]. Mimicry between amino acid sequences in islet autoantigens IA-2 (A) and GAD65 (B) and rotavirus genotype 3 viral protein 7 (VP7). https://doi.org/10.1371/journal.ppat.1007965.g001 In addition to mimicry with IA-2, a neighbouring sequence in VP7 (aa 17–25) (Fig 1B) had 78% identity and 100% similarity over 9 aa with a known HLA-DR4-restricted T-cell epitope in GAD65 [7]. [...]these IA-2 and GAD65 DR4-restricted epitopes encompassed T-cell epitopes for HLA class I–restricted CD8+ T cells in T1D [10], for which we coined the term “combitope.” Population-level data suggest RV vaccination may be associated with a decrease in the incidence of T1D The live oral RV vaccines Rotarix (G1P[8], monovalent, GSK) and RotaTeq (G1-4, P[8], pentavalent, Merck