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Viruses Cause Type 1 Diabetes in Animals
Author(s) -
YOON JIWON,
JUN HEESOOK
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1375.021
Subject(s) - virus , virology , immune system , biology , pathogenesis , diabetes mellitus , titer , viral replication , effector , immunology , endocrinology
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.