Tax protein of human T-cell leukaemia virus type 1 induces interleukin 17 gene expression in T cells.
Tax protein of human T-cell leukaemia virus type 1 (HTLV-1) induces the expression of several cellular genes that are involved in T cell activation and proliferation. In this study, it was observed that Tax upregulated the expression of human interleukin 17 (IL17), a cytokine mainly produced by activated CD4(+) memory T cells. Indeed, IL17 mRNA was highly expressed in HTLV-1-infected T cells as well as in Tax-expressing Jurkat T cells, whereas it was not detectable in HTLV-1-negative T cell lines. The clinical relevance of these observations was further demonstrated by quantitative assessment of IL17 expression in lymphocytes isolated from one HTLV-1-infected patient. To define the transcriptional activation of the IL17 gene by Tax, the 5'-flanking region of this gene was cloned and a reporter gene analysis performed. The presence of a Tax-responsive region spanning 614 bp upstream of the initiation start site was identified, in HeLa as well as in Jurkat cells, stimulated with phorbol myristate acetate and Ca(2+) ionophore. Finally, Tax mutants were used to show that the transcriptional activation of the IL17 promoter by Tax was dependent on the CREB/ATF pathway. As IL17 upregulates the expression of several pro-inflammatory cytokines, these observations provide new insights into the involvement of the Tax protein in the pathophysiology of HTLV-1-associated inflammatory disorders.
Dodon
Madeleine Duc
MD
Virologie Humaine INSERM-U412, Ecole Normale Supérieure de Lyon, IFR 128 BioSciences Lyon-Gerland, 46 allée d'Italie, 69364 Lyon Cedex 07, France.
Li
Zhenlin
Z
Biologie Moléculaire de la Différenciation, Université Paris 7 Denis Diderot, 2 place Jussieu, case 7136, 75251 Paris Cedex 05, France.
Hamaia
Samir
S
Virologie Humaine INSERM-U412, Ecole Normale Supérieure de Lyon, IFR 128 BioSciences Lyon-Gerland, 46 allée d'Italie, 69364 Lyon Cedex 07, France.
Gazzolo
Louis
L
Virologie Humaine INSERM-U412, Ecole Normale Supérieure de Lyon, IFR 128 BioSciences Lyon-Gerland, 46 allée d'Italie, 69364 Lyon Cedex 07, France.
D001483:Base Sequence; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019256:Cadmium Chloride / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000276:immunology*; D016356:Gene Products, tax / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000235:genetics*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000235:genetics / Q000276:immunology
D017931:DNA Primers; D004268:DNA-Binding Proteins; D016356:Gene Products, tax; D020381:Interleukin-17; D012333:RNA, Messenger; D012367:RNA, Viral; D004247:DNA; D019256:Cadmium Chloride