HTLV-1 transactivator induces interleukin-2 receptor expression through an NF-kappa B-like factor.
Like other viruses that infect primate cells, the human T lymphotropic virus-I (HTLV-I) stimulates production of some host cell proteins. In particular, HTLV-I infected T cells synthesize interleukin-2 receptor alpha (IL-2R alpha) chain, which is probably induced through the mediation of the tat-I gene product of the virus. Activated T cells contain a trascription factor called NF-kappa B, which stimulates the expression of human immunodeficiency virus-1 (HIV-1) by binding to an 11-base-pair enhancer sequence called kappa B. We have now found evidence that a similar transcription factor is involved in the induction of IL-2R alpha expression by tat-I. We have identified a sequence upstream of IL-2R alpha which is the same as the kappa B site at 9 of 11 base pairs, competes for binding to the kappa B sequence, and serves as a tat-I responsive element when multiple copies are inserted upstream of a heterologous promoter. The tat-I product also induces kappa B and the IL-2R alpha kappa B binding activity in transfected Jurkat T lymphoid leukaemia cells. Both HTLV-I and HIV-1 thus interact with NF-kappa B-like transcription factors which might normally regulate expression of a growth factor receptor gene.
Leung
K
K
Howard Hughes Medical Institute, University of Michigan Medical Center, Department of Internal Medicine, Ann Arbor 48109.
Nabel
G J
GJ
D001483:Base Sequence; D017977:Deltaretrovirus / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D015696:Gene Products, tat; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D008969:Molecular Sequence Data; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D015375:Receptors, Interleukin-2; D014157:Transcription Factors / Q000235:genetics*
D015696:Gene Products, tat; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D014157:Transcription Factors