PATHOGENESIS AND EVOLUTION OF HUMAN T CELL LEUKEMIA/LYMPHOTROPIC VIRUSES

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Part of the study of human T-cell leukemia/lymphotropic virus type 1 (HTLV-I) and simian T-cell leukemia virus type 1 (STLV-I) molecular evolution has been completed. Further analysis of STLV-I from Asian monkey species and pygmy chimpanzees has revealed the presence of a novel virus which is related to HTLV-I and HTLV-II. This virus has been isolated and its genetic characterization is in progress. Major emphasis has been on the functional role of the HTLV-I p12 protein, which is correlated genetically and functionally to the bovine papillomavirus 1 (BPV-1) E5 oncoprotein. Further, this small protein, which is located in the golgi complex, binds to a resident protein of the golgi complex, the 16 kilodalton subunit of the proton H+ vacuolar ATPase. Increasing evidence suggests that some viral proteins (E5 of BPV, gp55 of spleen focus forming virus) might function by binding to growth factor receptors and mimic natural ligand function. The possible role of p12(I) in HTLV-I transformation of human T-cells has been investigated by testing its binding to the alpha, beta and gamma chains of the interleukin 2 receptor (IL-2R). The p12 binds specifically to the IL-2 beta and gamma but not to the alpha chains. Mapping of the binding domain of the IL-2 beta chains has revealed that the p12 protein binds to the acidic rich region of the beta chains which also interacts with the p56(lck), a tyrosine kinase expressed mainly in T-cells. Moreover, the p12(I) protein binds to the cytoplasmic or transmembrane portions of the IL-2R gamma chain. Experiments to address the functional relevance of these findings are in progress.