EMC virus has provided the most useful animal model for virus-induced type 1 diabetes. Development of diabetes depends on many factors including virus strain, challenge dose, host factors such as genetic background, sex, immunoprotective function, inflammatory responses with macrophages, cytokines, chemokines, and chemical mediators. Autoimmunity induction is not likely to be a factor in this model, though a hit-and-run event cannot be excluded. Most importantly, the difference between the diabetogenic strain D (EMC-D) and the non-diabetogenic strain B (EMC-B) virus depends on only one amino acid change due to single point mutation of “A” to “G” at position 3155 (Thr-776 to Ala-776), suggesting that possible acquisition of diabetogenicity may occur often among environmental “non-diabetogenic” viruses. Although susceptibility to the EMC-D virus-induced diabetes depends on the genetic background of mice, the genetic determinants of the host remain to be elucidated. Clarification of the pathogenesis of EMC virus-induced diabetes will not only promote a better understanding of the mechanisms of virus-induced diabetes in general, but will also contribute to the development of new protective strategies against viral diabetes.
KeywordsObesity Superoxide Interferon Alanine Hyperglycemia
The authors thank Professor Takehiko Sasazuki for his helpful advice. We also thank Dr. Chiri Nagatsuka and Mrs Arisa Moroishi for their help in the preparation of the manuscript. Financial support by Ministry of Health, Labour and Welfare of Japan is acknowledged.
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