Human T cell lymphotropic virus type I Tax protein trans-activates interleukin 15 gene transcription through an NF-kappaB site.
Interleukin 15 (IL-15) mRNA is expressed in a wide variety of tissue types. However, with the exception of some T cell lines, IL-15 transcript expression has not been described in T cells. Herein we demonstrate that IL-15 mRNA can be detected in freshly isolated normal T cells and T cell lines. Furthermore, its expression is 3- to 4-fold higher in human T cell lymphotropic virus type I (HTLV-I)-infected T cells. By using reporter constructs bearing the 5' regulatory region of the IL-15 gene, we observed a positive correlation between HTLV-I Tax protein expression and IL-15 promoter activity in HTLV-I-infected T cells. Additionally, by using a Jurkat T cell transfectant that expresses Tax under an inducible promoter, we demonstrated that the expression of IL-15 mRNA increased 3-fold as Tax was expressed, suggesting that the Tax protein activates IL-15 transcription. An NF-kappaB consensus sequence is located at the -75 and -65 region of the IL-15 5' regulatory region. Mutations in the NF-kappaB motif or deletion of this sequence abrogated the promoter activity in both HTLV-I-positive and Jurkat Tax-transfectant cells. These data represent evidence for trans-activation of the IL-15 gene by the HTLV-I Tax protein through an NF-kappaB motif and suggest a potential role for IL-15 in HTLV-I-associated diseases such as adult T cell leukemia and HTLV-I-associated myopathy/tropical spastic paraparesis.
Azimi
N
N
Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. nazli@helix.nih.gov
Brown
K
K
Bamford
R N
RN
Tagaya
Y
Y
Siebenlist
U
U
Waldmann
T A
TA
D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D016356:Gene Products, tax / Q000096:biosynthesis / Q000378:metabolism*; D017930:Genes, Reporter; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000235:genetics; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D016356:Gene Products, tax; D019409:Interleukin-15; D016328:NF-kappa B; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins