Interactions between bovine retroviruses and the host immune system

Isaacson, Jeffrey
Major Professor
James A. Roth
Committee Member
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Veterinary Microbiology and Preventive Medicine

Immunological aspects of experimental infection of cattle with bovine immunodeficiency virus (BIV) and/or bovine leukemia virus (BLV) were studied. The specificity and kinetics of antibody responses to BIV antigens were determined by immunoblot analysis using two BIV recombinant fusion proteins expressed in E. coli. Sera from all eight BIV-infected cattle reacted to a p26-containing protein by four weeks post-inoculation (p.i.), but this reactivity decreased dramatically in seven cattle by six months post-inoculation. In contrast, reactivity to a protein containing the amino terminus of BIV gp42 persisted in all animals throughout the four year study. BIV could be isolated from peripheral blood mononuclear cells (PBMC) of all animals during the period of declining p26-specific antibodies. However, there was no obvious increase in virus recovery during this period, nor were any p26-containing circulating immune complexes detected by immunoprecipitation. Therefore, the antibody loss did not appear to be attributable to an increasing p26 antigenemia. These findings also suggest that seroepidemiological surveys that rely on detection of antibodies to p26 may underestimate the true prevalence of BIV. Because there was no evidence of immunosuppressive disease in these cattle, it was hypothesized that a suppression of antigen-specific immune responses contributed to the loss of p26-specific antibodies. Humoral responses to vaccination with tetanus toxoid (TT) were determined, as were lymphocyte proliferative responses to TT, allogeneic cells, and concanavalin A. Cattle infected with BIV and BLV, or BLV only, were also included in this study to examine possible viral interactions. The only consistent BIV effect was a reduction in responses to concanavalin A. However, BLV-infected cattle had significantly enhanced secondary antibody responses to TT and bovine herpes virus-1. Although only one BLV-infected animal was persistently lymphocytotic, circulating B cell and CD4+ T cell numbers were generally increased in BLV-infected cattle. There was also evidence for increased lymphocyte activation in BLV-infected cattle, including: (1) increased percentage of B cells expressing MHCII in freshly isolated PBMC; (2) increased percentage of B cells expressing CD25 and; (3) increased percentage of T cells expressing MHCII following short term culture of PBMC. These findings suggest that BLV may induce a generalized lymphocyte activation.