Modulation of apoptosis during HTLV-1-mediated immortalization process in vitro.
Suppression of apoptosis has been proposed as a mechanism involved in the transforming action of human T-cell leukemia/lymphotropic virus type-1 (HTLV-1). However, there is evidence that HTLV-1 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 HTLV-1 infection in vitro. High levels of apoptosis in HTLV-1 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 IL-2 in the medium was replaced by IL-4, allowing the cells to be efficiently infected by HTLV-1 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 HTLV-1, but apoptosis was only partly reduced by caspase inhibitors. Even if spontaneous apoptosis was relatively low in long-term cultures of PBLs immortalized by HTLV-1 in vitro, Fas death-receptor expression and function were well conserved. These observations provide a new rationale for explaining the dual effect of HTLV-1 in controlling apoptosis.
Matteucci
Claudia
C
Department of Experimental Medicine and Biochemical Science, University of Rome Tor Vergata, Rome, Italy.
Balestrieri
Emanuela
E
Macchi
Beatrice
B
Mastino
Antonio
A
D017209:Apoptosis / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000821:virology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral / Q000502:physiology*; D004789:Enzyme Activation; D016679:Genome, Viral; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000473:pathology / Q000821:virology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019014:fas Receptor / Q000502:physiology
D019014:fas Receptor; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases