Viruses in type 1 diabetes: brief review.
Type 1 diabetes results from the progressive destruction of insulin-producing pancreatic beta cells. Although the etiology of type 1 diabetes is believed to have a major genetic component, studies on the risk of developing type 1 diabetes suggest that environmental factors, such as viruses, may be important etiological determinants. Among the viruses, the most clear and unequivocal evidence that a virus induces type 1 diabetes in animals comes 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 the activated macrophages such as interleukin-1Beta, tumor necrosis factor-alpha, and nitric oxide play a critical role in the destruction of residual beta cells. KRV causes autoimmune type 1 diabetes in diabetes resistant-BioBreeding rats by breakdown of immune balance, including the preferential activation of effector T cells, such as Th1-like CD45RC+CD4+ T cells and CD8+ T cells, and down-regulation of Th2-like CD45RC-CD4+ and CD4+CD25+ T cells, rather than by direct infection of pancreatic beta cells.
Yoon
Ji-Won
JW
Center for Immunologic Research, Bligh Cancer Research Laboratories, Department of Microbiology and Immunology, The Chicago Medical School, North Chicago, IL, USA.
Jun
Hee-Sook
HS
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000821:virology*; D004195:Disease Models, Animal; D004686:Encephalomyocarditis virus / Q000472:pathogenicity*; D051379:Mice; D017992:Parvovirus / Q000472:pathogenicity*; D051381:Rats; D014777:Virus Diseases / Q000150:complications* / Q000473:pathology