Many auto-immune diseases are thought to be triggered by viral infections. In particular auto-immune diabetes and myocarditis are said to follow infections with enteroviruses. Histopathologic studies indicate that mumps and adenoviruses are viruses associated with myocarditis. In addition the Group B Coxsackie viruses have been isolated from patients who subsequently develop diabetes or myocarditis. Studies of humans with acute myocarditis and diabetes indicate the infiltrating T cells have a restricted usage of T-cell receptor genes suggesting that they may be directed at a particular antigen. Animal models indicate that both auto-immune diabetes and myocarditis can be initiated by Coxsackie B viruses. In addition to evidence that T cells can transfer the disease, a role of cytokines has been postulated for auto-immune diabetes and myocarditis. Studies in knock-out mice indicate a role for chemokines in the initiation of the inflammatory process that leads to Coxsackie B virus induced myocarditis. Hypotheses concerning the pathogenesis of auto-immune responses have generally focused on either a viral epitope mimicking a cellular protein (e.g. the GAD protein and a Coxsackie B4 protein), or suggested that the inflammatory response stimulated by the infectious event might damage the cell causing inflammatory changes that subsequently result in the generation of an immune response to host tissues. Whether the inflammation stimulates T cells that recognize host proteins or there is persistence of viral proteins has been hard to define in most model systems. In addition it is unclear how the type of auto- immune response relates to the tropism of the viral agent. We have recently defined a host cell surface protein that serves as the receptor for all group B Coxsackie viruses, the fiber binding protein of most adenoviruses, and a major determinant in mumps infection. The distribution of this protein suggests that its expression correlates with the ability of these viruses to induce auto-immune diseases. We plan to define the role of this protein in the induction of auto-immune disease and use transgenic and knock-out mice to define the mechanisms by which viruses stimulate autoimmune responses.
