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LABORATORY ANIMALS --- RODENTS

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LABORATORY ANIMALS --- SWINE

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Chlamydia --- Infection --- In vivo experimentation --- Laboratory animals --- Immune response

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Animal diseases --- Carcinogens --- Laboratory experimentation --- Cattle --- viruses. --- viruses --- Laboratory animals

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The relative importance of cell proliferation versus apoptosis during pathogenesis induced by the HTLV-1 and BLV oncoviruses (Human T-Lymphotropic Virus type 1 and Bovine Leukemia Virus) has been difficult to assess due to conflicting data from a range of in vitro and ex vivo experimental systems. Here, we aim to resolve this issue by studying the cell dynamics, in vivo, in three animal models of HTLV-1 : (i) BLV-infected sheep, (ii) BLV-infected cattle and (iii) Saimiri sciureus infected with HTLV-1. In all three systems, we used the same method based on the intravenous injection of bromodeoxyuridine. In BLV-infected sheep, we show that B-lymphocytes proliferate significantly faster than in uninfected controls. This difference in proliferation became even more evident at the terminal neoplastic stage of the disease. In contrast, the rates of cell death were not significantly different between aleukemic BLV-infected and control sheep. We conclude that the increase in the number of B cells during BLV-induced lymphocytosis results from higher proliferation rates but is not due to a significant decrease in apoptosis. In this model, we have also shown that the primo-infection period is associated with a transient B cell lymphocytosis resulting at least, in part, in an increase of B cell proliferation. In the second model, persistently lymphocytotic cattle infected with BLV, the B-cell turnover is characterized by a combination of a reduction in proliferation as well as a default in cell death. Finally, in Saimiri sciureus infected by HTLV-1, the turnover of the CD4-positive lymphocytes is unaltered. However, at the leukemic stage, the proliferation rate was reduced in a leukemic monkey. In summary, we have quantified the dynamic parameters associated with oncoviral pathogenesis in three experimental systems. These data are important for understanding the processes of leukemogenesis and open new prospects for therapy.

Sheep --- Sheep --- Cattle --- Cattle --- Laboratory animals --- Laboratory animals --- Bovine leukosis --- Bovine leukosis --- cell division --- cell division --- apoptosis --- apoptosis --- pathogenesis --- pathogenesis