This collaborative project established an animal model of HTLV-I associated disease in nonhuman primates with a primary HTLV-I viral isolate, derived from a human patient with HTLV-I associated tropical spastic paraparesis (TSP). Two of three inoculated rhesus macaques became infected and showed signs of disease. One animal presented with a findings identical to that in the original patient, with muscle atrophy, polymyositis, and arthritis, (manuscript published). The second animal was dually infected with SIV and developed signs suggestive of smoldering HTLV-I induced leukemia in the presence of SIV immunodeficiency disease. Four of five additional HTLV-I inoculated animals are asymptomatic but show evidence of persistent infection by HTLV-I PCR and increased lymphocytosis. The fifth animal is culture and PCR negative with an associated strong humoral response, as determined by western blot analysis. These results suggest that immune responses are important in controlling HTLV-I virus expression in the macaque model. We want to define the immune mechanism of this control. We have now extended our characterization of immune responses to that of cytotoxic cell mediated response. In collaboration with Dr. Larry Wilson, autologous transformed B cell lines from each animal were generated and are now stably cryopreserved. We have also obtained several HTLV-I gene specific - vaccinia virus constructs. These two reagents are now ready to be used to characterize the presence and nature of cytotoxic T lymphocytes in the control of HTLV-I in vivo. FUNDING Base Grant, Venture Research PUBLICATIONS Beilke M.A., Traina-Dorge VL, England JD, Blanchard J (1996) Polymyositis, Arthritis, and Uveitis in a macaque experimentally infected with HTLV-I. Arth. & Rheum. 39(4):610-615.
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