Integration of bovine leukaemia virus at all stages of enzootic bovine leukosis

Abstract

Integration of bovine leukaemia virus DNA was investigated at all stages of infection in cattle. We report here the detection of integrated proviral DNA in the majority of antibody positive animals without lymphocytosis. In all but one case virus was integrated at a number of different sites. Hybridization analysis failed to detect proviral sequences in animals shown to be BLV antibody-negative by the Agar Gel Immunodiffusion assay. The pattern of integration in leukocytes from animals with persistent lymphocytosis was similar to that in sero-positive animals without lymphocytosis in that multiple sites of integration were evident. As reported by others only one or a few sites of integration were detected in tumours from enzootic bovine leukosis animals. Tumours from different sites in individual animals were either monoclonal or oligoclonal.

Bovine leukemia virus gene expression in vivo

“…Transcripts for the envelope and the full-length RNAs were present in trace levels. The pattern of proviral integration in lymphocytes from animals with PL has been reported to be very similar to that in lymphocytes from seropositive animals without PL (2). Thus, it seems that the differences between aleukemic and PL animals observed here reflect differential transcriptional processing.…”

Enzootic bovine leukosis in a two-month-old calf

“…However, the BLV genome and antibody are detectable in some sporadic bovine leukosis (SBL) cases, including the juvenile form, which was unrelated to BLV infection (Jacobs et al, 1992). The confirmation of only one or a few sites of BLV integration within a sampled tumor tissue is diagnostic of EBL because EBL tumors are mono-or oligoclonal in origin (Kettmann et al, 1980;Kettmann et al, 1983;Coulston et al, 1991;Murakami et al, 2011). In the present study, we investigated a case of EBL in a two-month-old calf diagnosed by an integration site analysis of tumor tissues.…”

Detection of monoclonal integration of bovine leukemia virus proviral DNA as a malignant marker in two enzootic bovine leukosis cases with difficult clinical diagnosis

“…This finding suggests the monoclonal proliferation of lymphocytes in patients with ATL and is used as a marker of malignant transformation of infected lymphocytes [ 4 , 15 ]. Similarly, integration of BLV has also been studied in cattle with EBL [ 6 , 8 , 9 , 10 , 11 ]. Proviral DNA reportedly integrates at one or a few sites into the genomes of neoplastic cells in host cattle with lymphosarcoma [ 8 , 11 ].…”

“…The digested DNA was run on 1.0% agarose gels at 50 V for 7.5 hr. After electrophoresis and washing the gel with distilled water, DNA fragments were transferred from agarose gels to a hydrophobic polyvinylidene difluoride (PVDF) membrane (RPN303B; Amersham Hybond TM -P, GE Healthcare, Buckinghamshire, U.K.), as described in a previous report [ 6 ].…”

“…Since BLV randomly integrates into the genomic DNA of B-lymphocytes [ 19 ], polyclonal integration of BLV proviral DNA into the host genome should be observed in cattle without tumors, including clinically normal PL cattle or BLV carriers, as assessed by Southern blot [ 6 , 8 , 9 ]. Yet, once malignant transformation of lymphocytes occurs, B lymphocytes undergo monoclonal proliferation, and only DNA fragments of a specific length are amplified [ 6 , 8 , 9 ]. Thus, monoclonal proliferation of B-lymphocytes would result in one or several distinct bands in EBL samples.…”