Interleukin (IL) 15/IL-T production by the adult T-cell leukemia cell line HuT-102 is associated with a human T-cell lymphotrophic virus type I region /IL-15 fusion message that lacks many upstream AUGs that normally attenuates IL-15 mRNA translation

Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2897-902. doi: 10.1073/pnas.93.7.2897.

Abstract

We reported previously that the human T-cell lymphotrophic virus type I (HTLV-I)-associated adult T-cell leukemia line HuT-102 produces a cytokine designated interleukin (IL) T that requires interleukin (IL) 2 receptor beta-subunit expression for its action. Using anti-cytokine antibodies, we demonstrated that IL-T is identical to the simultaneously described IL-15. When compared to activated monocytes, IL-15 mRNA expression was 6- to 10-fold greater in HuT-102 cells. The predominant IL-15 message from HuT-102 is a chimeric mRNA joining a segment of the R region of the long terminal repeat of HTLV-I and the 5'-untranslated region (UTR) of IL-15. Normally, by alternative splicing, this 118-nucleotide R element represents the most 5' region of several HTLV-I transcripts including tax, rex, and env. The introduction of the R element eliminated over 200 nucleotides of the IL-15 5'-UTR, including 8 of 10 upstream AUGs that are present in normal IL-15 messages. On analysis of the 5'-UTR of normal IL-15, we demonstrated that the presence of these 10 upstream AUGs interferes with IL-15 mRNA translation. Thus, IL-15 synthesis by the adult T-cell leukemia line HuT- 102 involves an increase in IL-15 mRNA transcription and translation secondary to the production of an HTLV-I R element fusion message that lacks many upstream AUGs.

MeSH terms

  • Adult
  • Base Sequence
  • Cell Line
  • Codon
  • Gene Expression Regulation, Viral*
  • Human T-lymphotropic virus 1 / genetics
  • Human T-lymphotropic virus 1 / immunology*
  • Humans
  • Interleukin-15
  • Interleukins / biosynthesis*
  • Leukemia-Lymphoma, Adult T-Cell / immunology*
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Monocytes / immunology
  • Protein Biosynthesis*
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins / biosynthesis*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Codon
  • Interleukin-15
  • Interleukins
  • Lipopolysaccharides
  • RNA, Messenger
  • Recombinant Fusion Proteins

Associated data

  • GENBANK/S81555