Genomic integration of bovine leukemia provirus and lack of viral RNA expression in the target cells of cattle with different responses to BLV infection.

Enzootic bovine leukosis (EBL) is a contagious lymphoproliferative disease whose etiological agent is a retrovirus, the bovine leukemia virus (BLV). EBL is a complex disease. So on after infection a strong humoral antibody response develops and persists for the animal 's entire life. Such BLV-infected cattle can remain asymptomatic virus carriers for many years. They can also at a given time develop persistent lymphocytosis (PL) characterized by a permanent large number of peripheral lymphocytes. A variable but always significant percentage of PL animals develop lymphoid tumors, the terminal tumor phase of EBL. The remnant tumor cases develop suddenly in BLV carriers without any previous hematologic disorder. In general, the fate of BLV -infected animals is variable and depends upon several factors, including age, genetic make-up, environmental factors, and immunologic surveillance (see Burny et al. 1980 for a review). In the present investigation we studied BLV integration sites in DNA preparations from target tissues of BLV -infected animals and viral RNA expression in the same cells. DNA was digested by bacterial restriction endonucleases and submitted to electrophoresis in agarose gels. After transfer to nitrocellulose paper, the DNA fragments were annealed to a specific BLV e2p) cDNA probe. Genomic DNA fragments containing viral information appear after autoradiographic development as individual bands and sometimes as smears. The results of OUT study allow comparison of BLV provirus integration and viral RNA expression in leucocytes of animals showing different responses to BLV infection, namely, in asymptomatic BLV carriers (Ab+ änimals), animals in PL (PL + animals), and tumor cases (T+ animals). Our major findings are: (1) No BLV proviral sequences are detected in Ab + cases by the technique used; (2) Circulating leucocytes of PL animals accomodate BLV provirus at many possible sites; (3) Lymphocytes infected by BLV and found in EBL tumors constitute monoclonal populations of cells carrying one copy of the proviral genome which is integrated at one genomic site; and (4) In the vast majority of cases studied, no viral RNA expression was detectable in the lymphoid tumor cells or circulating leucocytes of affected animals.