The recently discovered human T-cell leukemia virus (HTLV) types I and II are associated with forms of human leukemia and lymphoma. Lymphomas have been the most frequently observed neoplasm in the NERPRC macaque cololy and eight of ten NERPRC macques with lymphomas or lymphoproliferative disorders had antibodies reactive with HTLV. T-cell lymphotropic viruses of macaques (MaTLV) will be isolated. The isolates will be characterized in terms of ultrastructural features, reverse transcriptase activity and cell tropism. The in vitro host range of MaTLV isolates will be determined with particular emphasis on its ability to infect and transform a variety of human and monkey cells. Verification that isolates are related to HTLV will be obtained by reactivity of antigenic proteins in infected cells with defined sera and by hybridization of DNA from infected cells with cloned HTLV DNA. The major proteins of MaTLV will be identified by polyacrylamide gel electrophoresis of purified virions. Viral proteins will be further characterized in terms of their glycosylation, the role of cellular processing in their production and their relatedness to the major proteins of HTLVI and II. Major antigens will be genetically mapped by radiolabel sequencing techniques. The relatedness of MaTLV to HTLVI and II will be determined by Southern blot hybridization of DNA from infected cells. Cloned MaTLV DNA will be prepared and used for restriction endonuclease mapping, for analysis of various isolates and for detection of viral genomes in lymphoma DNAs. Cloned MaTLV DNA will also be used for detailed comparisons with HTLVI and II by restriction site alignments and degree of homology along the genome. To investigate the role of MaTLV in macaque disease, seroepidemiologic studies will be conducted to determine age of exposure, modes of transmission and sex predisposition to infection. A search for viral genetic information in lymphomas will be performed. Attempts will be made to induce disease in naive macaques. Studies to date have indicated numerous parallels between the human and macaque systems; characterization of this virus and its biology in the macaque host will contribute significantly to our knowledge of the HTLV family. If lymphomas or other disease can be induced in macaques by experimental infection with MaTLV, various approaches to vaccination and therapeutic intervention can be studied in a meaningful manner.
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