Bovine leukemia virus interferes with the cellular mechanisms of apoptosis
1997
Dequiedt, F.
For multicellular organisms, apoptosis is an efficient way of eliminating cells which have been infected by a virus. In this work, the dysregulation of physiological apoptotic processes as an event promoting bovine leukemia virus (BLVD-induced leukemogenesis was investigated. Owing to the major role of p53 in the apoptotic mechanisms, the genes coding for the ovine and bovine p53 proteins were cloned and characterized. Sequence analyses have shown that tumors development in BLV-infected cattle is often associated with mutations within the p53 gene. On the other hand, no p53 genomic alteration can be related to the BLV-induced tumorigenesis. These results have demonstrated that different molecular mechanisms are involved during BLV leukemogenesis in the two hosts and could also explain the differences observed in disease susceptibility of these two species. Indeed, whereas a small number of infected cattle develop leukemia after long latency periods (five to ten years), a leukemia occurs in the majority of infected sheep within three years post-infection. The apoptotic processes that take place in BLV-infected animals were then investigated. We have enlightened a drastic reduction of the occurrence of apoptosis during cultivation of peripheral blood mononuclear cells isolated from infected animals. This reduction appeared to result from a direct protection conferred by the virus to the infected cells as well as from an indirect rescue of the uninfected cells. In summary, our results show the existence of a particular strategy developed by the bovine leukemia virus to interfere with the apoptotic processes in vivo.
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