Summary auto-generated
Bovine leukaemia virus (BLV) is a retrovirus that causes persistent B lymphocyte expansion and lymphosarcoma in infected animals. This study investigated mechanisms of BLV-induced lymphocytosis in experimentally infected sheep by analyzing B cell survival and proliferation. Researchers collected peripheral blood mononuclear cells from control, asymptomatic, and lymphocytotic sheep and measured apoptosis using the TUNEL assay and propidium iodide staining. B cells from lymphocytotic sheep showed significantly reduced spontaneous apoptosis (29% cell death) compared to asymptomatic (42%) and control sheep (57%) in 24-hour cultures. Virus capsid protein synthesis was predominantly detected in B cells, and the percentage of virus-producing B cells strongly correlated with B cell survival (R²=0.949), suggesting that BLV replication protects B lymphocytes from programmed cell death. However, this enhanced survival was not associated with increased Bcl-2 mRNA expression or changes in CD43 membrane protein levels. Fresh B cells from lymphocytotic sheep showed a slight increase in S-phase cycling (0.12–0.61%) compared to controls. The findings indicate that BLV-induced lymphocytosis involves both reduced B cell apoptosis and modest increases in B cell proliferation, with viral replication appearing to promote B lymphocyte survival through mechanisms independent of classical anti-apoptotic pathways.
Key findings
- B cells from BLV-infected lymphocytotic sheep show reduced spontaneous apoptosis (29% death) compared to control sheep (57% death) in ex vivo cultures
- BLV capsid protein production in B cells correlates strongly with enhanced B cell survival, suggesting viral replication protects lymphocytes from apoptosis
- Increased B cell survival in BLV infection occurs independently of Bcl-2 mRNA upregulation or CD43 expression changes
- Lymphocytotic sheep show modestly increased B cell proliferation (5-fold increase in S-phase cycling) compared to uninfected sheep
- BLV-induced lymphocytosis results from both decreased B cell apoptosis and increased proliferation, with viral expression appearing to suppress programmed cell death
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Abstract
I Schwartz-Cornil, N Chevallier, C Belloc, D Le Rhun, V Laine, M Berthelemy, A Mateo and D Levy
URA INRA d'Immuno Pathologie Cellulaire et Moleculaire, Maisons-Alfort, France. schwartz@jouy.inra.fr
Experimental inoculation of sheep with bovine leukaemia virus (BLV), a retrovirus homologous to the human T-lymphotropic virus type 1 (HTLV- 1), induces a chronic expansion of the B lymphocyte population (persistent lymphocytosis) and the development of a B cell leukaemia/lymphosarcoma syndrome. To gain insight into the mechanisms of BLV-induced lymphocytosis, we tested B cell survival capacity and cycling activity in peripheral blood mononuclear cells (PBMCs) from lymphocytotic, asymptomatic and control sheep. Interestingly, B cells from lymphocytotic sheep presented a lower level of spontaneous apoptosis (29%) in ex vivo cultures compared to that obtained with infected asymptomatic (42%) and control (57%/o) sheep PBMCs. Virus capsid (CA) synthesis was mainly found among surviving B cells and the percentage of CA-producing B cells correlated with the extent of B cell survival, indicating that BLV replication in B lymphocytes may promote protection from cell death. B cell survival was not linked with increases in expression of Bcl-2 mRNA or membrane leukosialin (CD43), although both are documented to be involved in some aspects of the B cell life-span. Finally, cell cycle analyses in freshly isolated PBMCs from lymphocytotic sheep revealed a slightly increased proportion of B cells in S phase compared to controls. Altogether, these data suggest that both BLV-induced B cell proliferation and extended survival are involved in the lymphocytotic stage encountered in BLV infection in sheep.