The proposed research aims to develop bovine immunodeficiency-like virus (BIV) as a potential model for the study of HIV pathogenesis. BIV has genetic and antigenic similarities to HIV-1. Calves will be experimentally inoculated with BIV and monitored for up to five years for clinical and pathological changes associated with BIV infection. Tissues and cells from infected calves will be examined for gross and microscopic changes. In situ hybridization and immunohistochemistry will be used to correlate any pathological changes with the presence of virus and to determine sites of viral infection. The effect of BIV on host immune competence will assessed using a battery of tests for lymphocyte, monocyte and neutrophil function. We will follow the development of BIV- specific antibody and correlate its presence with the course of clinical disease. Sera collected throughout the experimental period will be assays for BIV neutralizing antibody, for antibody to BIV-infected cells and for activity in an antibody-dependent cell-mediated cytotoxicity assay. Antibody titers will be correlated with clinical and pathological findings to detect a possible role for antibody in the pathogenesis of BIV infection. The in vivo consequences of concommitant viral infections will be studied by coinfecting calves with BIV and either a bovine herpesvirus (BHV) or bovine leukemia virus (BLV). Finally, we will explore viral variation as a potential mechanism of viral persistence. Sequential isolates of BIV will be recovered from infected calves and genetically characterized to determine the frequency and extent of viral variation. Isolates will be characterized in vitro as to antigenicity, host cell tropism and pathogenicity in order to better understand mechanisms of variant selection. The experiments outlined in this proposal will better define the biological complexities of an animal lentivirus infection which has received the little attention and which may provide unique opportunities for development and evaluation of therapeutic treatments and vaccine protocols in human and animal lentivirus infections.
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