Viruses Cause Type 1 Diabetes in Animals

: More than 10 viruses have been reported to be associated with the development of type 1 diabetes‐like symptoms in animals, with the best evidence coming from studies on the D variant of encephalomyocarditis (EMC‐D) virus in mice and Kilham rat virus (KRV) in rats. A high titer of EMC‐D viral infection results in the development of diabetes within 3 days, primarily due to the rapid destruction of β cells by viral replication within the cells. A low titer of EMC‐D viral infection results in the recruitment of macrophages to the islets. Soluble mediators produced by activated macrophages play a critical role in the destruction of residual β cells. A single amino acid at position 776 of the EMC viral genome controls the diabetogenicity of the virus. In contrast, KRV causes autoimmune type 1 diabetes in diabetes‐resistant BioBreeding (DR‐BB) rats without direct infection of β cells. Macrophages play an important role in the development of diabetes in KRV‐infected DR‐BB rats. As well, KRV infection preferentially activates effector T cells, such as Th1‐like CD45RC+CD4+ T cells and CD8+ T cells, and downregulates regulatory T cells, such as Th2‐like CD45RC−CD4+ T cells. This results in the breakdown of the immune balance, contributing to the development of diabetes in KRV‐infected DR‐BB rats.