Activation of Bcl-2 expression in human endothelial cells chronically expressing the human T-cell lymphotropic virus type I.
Programmed cell death (PCD) characteristically involves chromatin condensation, membrane blebbing, and DNA oligonucleosomal fragmentation. These events, collectively referred to as apoptosis, represent an active cell suicide mechanism that eliminates cellular threats including potentially cancerous or virus-infected cells. Various types of programmed cell death can be blocked by the proto-oncogene Bcl-2. Levels of this protein are consistently low or undetectable in human endothelial cells (EC), which are important for immunoregulation through their interactions with circulating lymphocytes and are potential targets for infection by virus-bearing T-cells. Accumulating evidence suggests that EC may be infected in vivo to play an important role in HTLV-I-associated neuromyelopathy. In the present study, we report the establishment and characterization of human endothelial cell lines stably transfected with an HTLV-I-derived molecular clone. We observed constitutive expression of HTLV-I genes coinciding with activated Bcl-2 expression. Transient transfection of EC with the viral transactivator Tax and a reporter construct Bcl-2 promoter-CAT did not result in a significant increase in CAT activity and suggests that, in EC, expression of a second viral protein might be required for Bcl-2 activation. Further, Tax-induced apoptosis in rat fibroblasts has been shown to be blocked by Bcl-2 expression. Thus, HTLV-I-mediated induction of Bcl-2 expression in EC may provide protection against viral-induced apoptosis or extend cellular survival and create a reservoir for viral gene expression.
Nicot
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C
Department of Microbiology and Immunology, Room B4125, 4301 Jones Bridge Road, Bethesda, Maryland 20814, USA.
Astier-Gin
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T
Guillemain
B
B
D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000502:physiology*; D005347:Fibroblasts; D016356:Gene Products, tax / Q000096:biosynthesis / Q000378:metabolism*; D005814:Genes, Viral; D019254:Genes, bcl-2; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014162:Transfection
D017931:DNA Primers; D016356:Gene Products, tax; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D015500:Chloramphenicol O-Acetyltransferase