COMPLETE BOVINE LEUKEMIA-VIRUS (BLV) PROVIRUS IS CONSERVED IN BLV-INFECTED CATTLE THROUGHOUT THE COURSE OF B-CELL LYMPHOSARCOMA DEVELOPMENT

Bovine leukemia virus (BLV) and human T-celi leukemia virus types 1 an d 2 (HTLV-1 and HTLV-2) belong to the same subfamily of oncoviruses. D efective HTLV-1 proviral genomes have been found in more than half of all patients with adult T-cell leukemia examined. We have characterize d the genomic structure of integrated BLV proviruses in peripheral blo od lymphocytes and tumor tissue taken from animals with lymphomas at v arious stages. Genomic Southern hybridization with SacI, which generat es two major fragments of BLV proviral DNA, yielded only bands that co rresponded to a full-size provirus in all of 23 cattle at the lymphoma stage and in 7 BLV-infected but healthy cattle. Long PCR with primers located in long terminal repeats clearly demonstrated that almost the complete provirus was retained in all of 27 cattle with lymphomas and in 19 infected but healthy cattle. However, in addition to a PCR prod uct that corresponded to a full-size provirus, a fragment shorter than that of the complete virus was produced in only one of the 27 animals with lymphomas. Moreover, when we performed conventional PCR with a v ariety of primers that spanned the entire BLV genome to detect even sm all defects, PCR products were produced that specifically covered the entire BLV genome in all of the 40 BLV-infected cattle tested. Therefo re, it appears` that at least one copy of the full-length BLV proviral genome was maintained in each animal throughout the course of the dis ease and, in addition, that either large or small deletions of provira l genomes may be very rare events in BLV-infected cattle.