Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2 Tax Oncoproteins Modulate Cell Cycle Progression and Apoptosis
Open Access
- 1 October 2004
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 78 (19) , 10399-10409
- https://doi.org/10.1128/jvi.78.19.10399-10409.2004
Abstract
Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia and lymphoma, an aggressive clonal malignancy of human CD4-bearing T lymphocytes. HTLV-2, although highly related to HTLV-1 at the molecular level, has not been conclusively linked to development of lymphoproliferative disorders. Differences between the biological activities of the respectivetaxgene products (Tax1 and Tax2) may be one factor which accounts for the differential pathogenicities associated with infection. To develop an in vitro model to investigate and compare the effects of constitutive expression of Tax1 and Tax2, Jurkat T-cell lines were infected with lentivirus vectors encoding Tax1 and Tax2 in conjunction with green fluorescent protein, and stably transduced clonal cell lines were generated by serial dilution in the absence of drug selection. Jurkat cells that constitutively express Tax1 and Tax2 (Tax1/Jurkat and Tax2/Jurkat, respectively) showed notably reduced kinetics of cellular replication, and Tax1 inhibited cellular replication to a higher degree in comparison to Tax2. Tax1 markedly activated transcription from the cdk inhibitor p21cip1/waf1promoter in comparison to Tax2, suggesting that upregulation of p21cip1/waf1may account for the differential inhibition of cellular replication kinetics displayed by Tax1/Jurkat and Tax2/Jurkat cells. The presence of binucleated and multinucleated cells, reminiscent of large lymphocytes with cleaved or cerebriform nuclei often seen in HTLV-1- and -2-seropositive patients, was noted in cultures expressing Tax1 and Tax2. Although Tax1 and Tax2 expression mediated elevated resistance to apoptosis in Jurkat cells after serum deprivation, Tax1 was unique in protection from apoptosis after exposure to camptothecin and etoposide, inhibitors of topoisomerase I and II, respectively. Characterization of the unique phenotypes displayed by Tax1 and Tax2 in vitro will provide information as to the relative roles of these oncoproteins and their contribution to HTLV-1 and -2 pathogenesis in vivo.Keywords
This publication has 67 references indexed in Scilit:
- Block of a Mitochondrial-Mediated Apoptotic Pathway in Tax-Expressing Murine FibroblastsExperimental Cell Research, 2001
- Accelerated G1 Phase Progression Induced by the Human T Cell Leukemia Virus Type I (HTLV-I) Tax OncoproteinPublished by Elsevier ,2001
- Phosphoinositide-3 kinase-PKB/Akt pathway activation is involved in fibroblast Rat-1 transformation by human T-cell leukemia virus type I taxOncogene, 2001
- Genetic Evidence of a Role for ATM in Functional Interaction between Human T-Cell Leukemia Virus Type 1 Tax and p53Journal of Virology, 2001
- Tax-Dependent Stimulation of G1Phase-Specific Cyclin-Dependent Kinases and Increased Expression of Signal Transduction Genes Characterize HTLV Type 1-Transformed T CellsAIDS Research and Human Retroviruses, 2000
- HTLV-1 Tax oncoprotein represses the p53-mediated trans-activation function through coactivator CBP sequestrationOncogene, 2000
- Human T cell lymphotropic virus type I genomic expression and impact on intracellular signaling pathways during neurodegenerative disease and leukemiaFrontiers in Bioscience-Landmark, 2000
- ICE-proteases mediate HTLV-I Tax-induced apoptotic T-cell deathOncogene, 1997
- HTLV-1 oncoprotein Tax deregulates transcription of cellular genes through multiple mechanismsZeitschrift für Krebsforschung und Klinische Onkologie, 1995
- Inhibition of Apoptosis in T Cells Expressing Human T Cell Leukemia Virus Type I TaxAIDS Research and Human Retroviruses, 1994