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 beta 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 beta 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 beta 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.
Yoon
Ji-Won
JW
Rosalind Franklin Comprehensive Diabetes Center, Chicago Medical School, North Chicago, IL 60064, USA.
Jun
Hee-Sook
HS
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000473:pathology / Q000821:virology*; D004195:Disease Models, Animal; D004686:Encephalomyocarditis virus / Q000472:pathogenicity*; D007515:Islets of Langerhans / Q000821:virology; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D017992:Parvovirus / Q000472:pathogenicity*; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology