Bovine Leukemia Virus-Induced Persistent Lymphocytosis in Cattle Does Not Correlate with Increased Ex Vivo Survival of B Lymphocytes

Abstract

Bovine leukemia virus (BLV) is an oncogenic retrovirus associated with B-cell lymphocytosis, leukemia, and lymphosarcoma in the ovine and bovine species. We have recently reported that in sheep, BLV protects the total population of peripheral blood mononuclear cells (PBMCs) from ex vivo spontaneous apoptosis. This global decrease in the apoptosis rates resulted from both direct and indirect mechanisms which allow extension of cell survival. Although sheep are not natural hosts for BLV, these animals are prone to develop virus-induced leukemia at very high frequencies. Most infected cattle, however, remain clinically healthy. This difference in the susceptibilities to development of leukemia in these two species might be related to alterations of the apoptotic processes. Therefore, we designed this study to unravel the mechanisms of programmed cell death in cattle. We have observed that PBMCs from persistently lymphocytotic BLV-infected cows were more susceptible to spontaneous ex vivo apoptosis than cells from uninfected or aleukemic animals. These higher apoptosis rates were the consequence of an increased proportion of B cells exhibiting lower survival abilities. About one-third of the BLV-expressing cells did not survive the ex vivo culture conditions, demonstrating that viral expression is not strictly associated with cell survival in cattle. Surprisingly, culture supernatants from persistently lymphocytotic cows exhibited efficient antiapoptotic properties on both uninfected bovine and uninfected ovine cells. It thus appears that indirect inhibition of cell death can occur even in the presence of high apoptosis rates. Together, these results demonstrate that the protection against spontaneous apoptosis associated with BLV is different in cattle and in sheep. The higher levels of ex vivo apoptosis occurring in cattle might indicate a decreased susceptibility to development of leukemia in vivo.

Cattle Infected with Bovine Leukaemia Virus may not only Develop Persistent B‐cell Lymphocytosis but also Persistent B‐cell Lymphopenia

“…Remarkably, these findings disagree with several reports that did not notice any changes in the B‐cell population of PL − animals (Gatei et al, 1989; Levkut et al, 1995; Dequiedt et al, 1999). To our knowledge, no reports exist describing a statistically significant reduction in B cells only.…”

“…In contrast, contradictory views exist on the distribution of B and T cells in the peripheral blood of BLVinfected cattle which are haematologically inconspicuous. Whereas in several investigations no differences in the percentage and number of B cells have been observed (Gatei et al, 1989;Sordillo et al, 1994;Levkut et al, 1995;Dequiedt et al, 1999;Lundberg and Splitter, 2000), a decrease in these cells has been detected by Meirom et al (1993).…”

Spontaneously proliferating lymphocytes from bovine leukaemia virus-infected, lymphocytotic cattle are not the virus-expressing lymphocytes, as these cells are delayed in G0/G1 of the cell cycle and are spared from apoptosis

“…Whether the proliferating B lymphocytes are infected with BLV is not known. In agreement with a previous report (Dequiedt et al , 1999 ) we observed that lymphocytes expressing BLV p24 during unstimulated culture were spared from apoptosis. Our results extend this observation and suggest that the ability of BLV expression to prevent apoptosis may be tied to its ability to arrest or delay cells in G 0 /G 1 of the cell cycle.…”

In vitro infection of cells of the monocytic/macrophage lineage with bovine leukaemia virus

“…Susceptibility to apoptosis associated with BLV infection seems to vary from one species to another. B cells from lymphocytotic sheep appear to be protected from ex vivo spontaneous programmed cell death (Dequiedt et al , 1997 ; Schwartz-Cornil et al , 1997 ), while PBMCs from persistently lymphocytotic BLV-infected cows are more susceptible to ex vivo apoptosis than PBMCs from uninfected or aleukaemic animals (Dequiedt et al , 1999 ). According to our results, primary macrophages from uninfected sheep and cows, infected in vitro with BLV, were similarly resistant to apoptosis.…”