Abstract
Suppression of apoptosis has been proposed as a mechanism involved in the transforming action of human Tโcell leukemia/lymphotropic virus typeโ1 (HTLVโ1). However, there is evidence that HTLVโ1 and its protein Tax also induce apoptosis. To resolve this apparent paradox, apoptosis was monitored in primary cultures of peripheral blood lymphocytes (PBLs) from healthy donors, following HTLVโ1 infection in vitro. High levels of apoptosis in HTLVโ1 infected cultures during the first weeks after infection were detected. Apoptosis was not related to the presence of uninfected cells, as revealed by a fluorescence in situ hybridization assay. Successively, a progressive decrease in apoptosis in infected cultures going towards immortalization, was observed. When ILโ2 in the medium was replaced by ILโ4, allowing the cells to be efficiently infected by HTLVโ1 but not immortalized, apoptosis levels tended to increase, instead of decreasing, with the ongoing time. The caspase cascade was remarkably activated in PBLs recently infected in vitro by HTLVโ1, but apoptosis was only partly reduced by caspase inhibitors. Even if spontaneous apoptosis was relatively low in longโterm cultures of PBLs immortalized by HTLVโ1 in vitro, Fas deathโreceptor expression and function were well conserved. These observations provide a new rationale for explaining the dual effect of HTLVโ1 in controlling apoptosis. J. Med. Virol. 74:473โ483, 2004. ยฉ 2004 WileyโLiss, Inc.