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Journal of Virology, December 2003, p. 13073-13083, Vol. 77, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.24.13073-13083.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Reduced Cell Turnover in Bovine Leukemia Virus-Infected, Persistently Lymphocytotic Cattle

Christophe Debacq,¹ Becca Asquith,² Michal Reichert,³ Arsène Burny,¹ Richard Kettmann,¹ and Luc Willems^1*

Molecular and Cellular Biology, FUSAGx, Gembloux, Belgium,¹ Department of Immunology, Imperial College School of Medicine, London, United Kingdom,² Department of Pathology, National Veterinary Research Institute, Pulawy, Poland³

Received 7 May 2003/ Accepted 3 September 2003

Although nucleotide analogs like bromodeoxyuridine have been extensively used to estimate cell proliferation in vivo, precise dynamic parameters are scarce essentially because of the lack of adequate mathematical models. Besides recent developments on T cell dynamics, the turnover rates of B lymphocytes are largely unknown particularly in the context of a virally induced pathological disorder. Here, we aim to resolve this issue by determining the rates of cell proliferation and death during the chronic stage of the bovine leukemia virus (BLV) infection, called bovine persistent lymphocytosis (PL). Our methodology is based on direct intravenous injection of bromodeoxyuridine in association with subsequent flow cytometry. By this in vivo approach, we show that the death rate of PL B lymphocytes is significantly reduced (average death rate, 0.057 day^-1 versus 0.156 day^-1 in the asymptomatic controls). Concomitantly, proliferation of the PL cells is also significantly restricted compared to the controls (average proliferation rate, 0.0046 day^-1 versus 0.0085 day^-1). We conclude that bovine PL is characterized by a decreased cell turnover resulting both from a reduction of cell death and an overall impairment of proliferation. The cell dynamic parameters differ from those measured in sheep, an experimental model for BLV infection. Finally, cells expressing p24 major capsid protein ex vivo were not BrdU positive, suggesting an immune selection against proliferating virus-positive lymphocytes. Based on a comparative leukemia approach, these observations might help to understand cell dynamics during other lymphoproliferative disease such as chronic lymphocytic leukemia or human T-cell lymphotropic virus-induced adult T-cell leukemia in humans.

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* Corresponding author. Mailing address: Department of Applied Biochemistry and Biology, Faculté Universitaire des Sciences Agronomiques (FUSAGx), 13 avenue Maréchal Juin, 5030 Gembloux, Belgium. Phone: 32-81-622157. Fax: 32-81-6133888. E-mail: Willems.l{at}fsagx.ac.be.

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Journal of Virology, December 2003, p. 13073-13083, Vol. 77, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.24.13073-13083.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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