Bovine leukemia virus (BLV) is an important, naturally occurring, endermic, retroviral disease of cattle, and a valuable comparative biomedical animal model of analogous human T cell lymphotropic retroviral (HTLV) infections. The overall objective of this proposal is to extend our understanding of basic properties of the host-viral relationship in BLV-infected cattle, so as to gain insight into similar mechanisms which might be operative in HTLV infections in man. The emphasis is directed toward elucidation of the mechanism responsible for viral latency and the induction and maintenance of leukemogenesis.
The specific aims are to: 1) Determine the ability of BLV to infect/immortalize bovine cells in vitro; 2) determine the target cell specificity of BLV in blood leukocyte subpopulations of naturally infected cattle in different stages of the infection; 3) determine if BLV-infected B cells and anti-BLV antibody producing cells are the same or separate populations; 4) determine the effect of BLV on lymphokine gene transcription in infected cell populations; 5) correlate the presence of BLV tat gene products with cell proliferation in BLV- infected cells, and determine the ability of the tat protein to enhance transcription of lymphokine genes, and; 6) establish lymphoblastoid cell lines from naturally occurring cases of enzootic bovine leukosis. A well characterize panel of monoclonal antibodies against bovine lymphoid cell subpopulations will e used to isolate and identify BLV-infected cell populations. Southern and northern nucleic acid hybridization techniques will be used to detect BLV proviral DNA, and the transcriptional activity of viral and lymphokine genes. An avidin-biotin complex immunocytochemical technique will be used to determine the number of BLV gp51 antigen- positive cells. A prokaryotic tat protein expression vector will be used to produce an antiserum for the detection of the tat protein and subsequent correlation with cell proliferation. An eukaryotic tat protein expression vector will be used for transfection of normal bovine cells for subsequent analysis of lymphokine expression. The uniqueness of this proposal derives from: 1) The careful application of contemporary techniques to elucidate the molecular mechanisms responsible for retroviral latency and leukemogenesis; 2) the utilization of a homologous system and naturally occurring infections as well as in vitro induced infections, and; 3) the implications for the pathogenesis of analogous HTLV and related retroviral infections in man where similar studies cannot be performed.
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