title: HTLV-1 positive and negative T cells cloned from infected individuals display telomerase and telomere genes deregulation that predominate in activated but untransformed CD4+ T cells.
abstract: Untransformed HTLV-1 positive CD4(+)  cells from infected individuals are selected for expressing tax and displaying morphological features consistent with telomere dysfunctions. We show that in resting HTLV-1 positive CD4(+)  cells cloned from patients, hTERT expression parallels tax expression and cell cycling. Upon activation, these cells dramatically augment tax expression, whereas their increase in telomerase activity is about 20 times lower than that of their uninfected counterpart. Activated HTLV-1 positive CD4(+)  but not uninfected CD4(+)  or CD8(+)  clones also repress the transcription of TRF1, TPP1, TANK1, POT1, DNA-PKc and Ku80. Both infected and uninfected lymphocytes from infected individuals shared common telomere gene deregulations toward a pattern consistent with premature senescence. ATLL cells displayed the highest telomerase activity (TA) whereas recovered a telomere gene transcriptome close to that of normal CD4(+)  cells. In conclusion HTLV-1-dependent telomere modulations seem involved in clonal expansion, immunosuppression, tumor initiation and progression.
authors: Université de Lyon, Oncovirologie et Biothérapies, Centre Léon Bérard, Lyon, France.
authors: Linda
authors: L
authors: Zane
authors: David
authors: D
authors: Sibon
authors: Valérie
authors: V
authors: Capraro
authors: Perrine
authors: P
authors: Galia
authors: Maroun
authors: M
authors: Karam
authors: Marie-Hélène
authors: MH
authors: Delfau-Larue
authors: Eric
authors: E
authors: Gilson
authors: Antoine
authors: A
authors: Gessain
authors: Olivier
authors: O
authors: Gout
authors: Olivier
authors: O
authors: Hermine
authors: Franck
authors: F
authors: Mortreux
authors: Eric
authors: E
authors: Wattel
mesh_terms: D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002999:Clone Cells; D017931:DNA Primers; D015490:HTLV-I Infections / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D006706:Homeostasis; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification*; D006801:Humans; D008213:Lymphocyte Activation; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000089804:Shelterin Complex; D019098:Telomerase / Q000235:genetics*; D016615:Telomere; D034501:Telomere-Binding Proteins; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: C495876:ACD protein, human; D017931:DNA Primers; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D019098:Telomerase