It is our hypothesis that acute or persistent virus infection can cause degenerative progressive diseases of neurons, endocrine cells, immunocompetent cells or cells of the renal glomeruli and choroid plexus. Such diseases, manifested in aging populations, occur through the basic mechanisms. The first relates to the ability of a virus to persist in specialized cells (i.e., neurons) and turn off or abrogate the differentiated or luxury function of these cells (i.e., neurotransmitters, peptide hormones). Included are viruses that are noncytopathic, that are associated with the formation of amyloid plaques, that deposit pigments in cells leading to injury and disease. The second mechanism relates to the formation and action of autoantibodies leading to cell injury. We propose that viruses can cause autoantibody through a process of """"""""molecular mimicry"""""""" and/or through the effects on B or T lymphocyte subsets. In the proposed venture, we intend to combine the skill of investigators with expertise in experimental and molecular biology, immunopathology, immunology, virology, neuropathology and cell biology. This group will study 1) persistent infection of neurons, endocrine and immunocompetent cells, 2) generation of amyloid plaques in scrapie infected mice, pigmentary neuronal degeneration in retrovirus infection of neurons and disease of immune complex or antitissue antibody types related to cross-reactive antigens, and 4) molecular mimicry between viral polypeptides and host cell antigens.
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