Coxsackievirus B1 Is Associated With Induction of -Cell Autoimmunity That Portends Type 1 Diabetes

O. H. Laitinen, H. Honkanen, O. Pakkanen, S. Oikarinen, M. M. Hankaniemi, H. Huhtala, T. Ruokoranta, V. Lecouturier, P. Andre, R. Harju, S. M. Virtanen, J. Lehtonen (+7 others)
2013 Diabetes  
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 which could be involved in the initiation of the disease process by screening neutralizing antibodies against 41 different enterovirus types in
more » ... 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 diabetespredictive 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 it 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 crossprotection 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. Page 22 of 38 Diabetes 23 The part of VP1 region of all 44 viruses was sequenced and the obtained sequences were blasted against the NCBI non-redundant nucleotide database. Phylogenetic analysis was done using Phylip program package version 3.69 (Felsenstein, J. 1993. PHYLIP: phylogeny inference package, version 3.69. University of Washington, Seattle). The phylogenetic tree was constructed using the Protdist program with the parameters of the Kimura 2 model and the amino acid matrix was processed with the Kitsch program. The consensus tree was treated with the Consense program. This analysis implies a close genetic relationship of the three CBV viruses which were associated with β-cell autoimmunity. Abbreviations of virus strains: E = Echovirus, CAV = Coxsackie virus A, CBV = Coxsackie virus B and EV = Enterovirus. Risk-associated CBV1 strain is indicated by R and protective CBV3 and CBV6 strains by P. The bootstrap confidence levels were analyzed with 1000 pseudoreplicate data sets and higher than 70% bootstrap levels were plotted onto the tree.
doi:10.2337/db13-0619 pmid:23974921 fatcat:hpdx73obrfexlbtwqsgmap5axu