VIRAL DETERMINANTS OF PATHOGENESIS BY FELVS AND HTLV-I

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Retroviruses are capable of inducing ablative as well as proliferative diseases of the lymphoreticular system. Induction of T-cell leukemia/lymphoma is associated in cats with infection with subgroups A and B Feline Leukemia Viruses (FeLV), and in humans with infection with Type I Human T-cell Lymphotrophic Viruses (HTLV-I). In contrast, subgroup C FeLVs will induce aplastic anemia in cats, and HTLV-III is the probable cause of AIDS in humans. Because the spectrum of disease induced by FeLV and HTLV is so similar, FeLV is considered to be the most appropriate animal model for virus-associated human malignancy and AIDS. I propose molecular and biological analyses of FeLV A, B and C and HTLV-I prototype viruses to define crucial aspects of their biological activity and the genetic features which determine these properties. Molecular studies will include transcription analysis, molecular cloning and DNA sequencing of natural virus isolates and generation of recombinent FeLV and FeLV/HTLV following in-vitro manipulation of cloned DNAs. Biological studies will include transfection and tests for transcriptional activity, virus production and ability to complement oncogenes in transformation of naive rat embryo fibroblasts. Certain viruses derived by transfection will also be inoculated into domestic cats to monitor pathogenic activity.