The primary objective of this research is to characterize factors which may influence viral replication and the lymphoproliferative changes induced by bovine immunodeficiency-like virus (BIV) infection in cattle. Factors to be studied include viral genetic variation, specificity of the antibody response, co-infection with bovine leukemia virus (BLV), and immunosuppression. BIV is a lentivirus which induces mild lymphoproliferative changes in cattle and is genetically and antigenically related to HIV-1. BLV is an oncovirus known to be a cause of bovine leukemia and lymphosarcoma and is structurally similar to HTLV-1. A major goal of this project is to determine if in vivo or in vitro co-infection with BIV and BLV alters the replication or pathogenesis of either virus. Animals which have been infected with either BIV, BLV, or both BIV and BLV will continue to be monitored from 2 through 6 years post infection for virus replication, specificity of the antibody response, immune competence and clinical and hematologic changes. Sequential virus isolates and serum samples obtained from these animals will be characterized as to antigenic specificity and will be correlated with viral replication in vivo. The interaction of BIV and BLV in co-infected cells in vitro will be characterized by quantitation of cell free virus, monitoring for expression of viral regulatory proteins, and transactivation of heterologous virus promoters using transient expression assays. The role of viral variation in the pathogenesis of BIV will be studied by comparing differences in in vivo pathologic effects and cell tropism in vitro with genetic differences in regulatory, structural, and envelop sequences of the viral genome. The similarities between BIV and HIV-1 and between BLV and HTLV-1 suggest that these are very promising domestic animal models for retroviral-associated human malignancies. Characterizing how the various factors described above contribute to the regulation of BIV viral replication and induction of lymphoproliferative changes will help in the basic understanding of retroviral-induced lymphoproliferative diseases.
