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Journal of Virology, February 1999, p. 1127-1137, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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

Franck Dequiedt,1,* Glenn H. Cantor,2 Valerie T. Hamilton,2 Suzanne M. Pritchard,2 William C. Davis,2 Pierre Kerkhofs,3 Arsène Burny,1,4 Richard Kettmann,1 and Lucas Willems1

Department of Applied Biochemistry and Biology, Molecular Biology and Animal Physiology Unit, Faculty of Agronomy, B5030 Gembloux,1 Veterinary and Agrochemical Research Centre, B1120 Uccle,3 and Department of Molecular Biology, University of Brussels, B1640 Rhode-St-Genèse,4 Belgium, and Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 991642

Received 19 June 1998/Accepted 9 October 1998

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.

* Corresponding author. Mailing address: Department of Applied Biochemistry and Biology, Molecular Biology and Animal Physiology Unit, Faculty of Agronomy, 13, Ave. Maréchal Juin, B5030 Gembloux, Belgium. Phone: 32-81-62-21-57. Fax: 32-81-61-38-88. E-mail: dequiedt.f{at}fsagx.ac.be.

Journal of Virology, February 1999, p. 1127-1137, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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