title: Stimulation of the human immunodeficiency virus type 1 enhancer by the human T-cell leukemia virus type I tax gene product involves the action of inducible cellular proteins.
abstract: The human immunodeficiency virus type 1 (HIV-1) preferentially infects CD4+ T lymphocytes and may exist as a latent provirus within these cells for extended periods. The transition to a productive retroviral infection results in T-cell death and clinically may lead to the acquired immune deficiency syndrome. Accelerated production of infectious HIV-1 virions appears to be closely linked to a heightened state of T-cell activation. The transactivator (Tax) protein of the type I human T-cell leukemia virus (HTLV-I) can produce such an activated T-cell phenotype and augments activity of the HIV-1 long terminal repeat. One Tax-responsive region within the HIV-1 long terminal repeat has been mapped to a locus composed of two 10-base-pair direct repeats sharing homology with the binding site for the eucaryotic transcription factor NF-kappaB (GGGACTTTCC). Tax-expressing Jurkat T cells contain one or more inducible cellular proteins that specifically associate with the HIV-1 enhancer at these binding sites. Microscale DNA affinity precipitation assays identified a Tax-inducible 86-kilodalton protein, HIVEN86A, as one of these HIV-1 enhancer-binding factors. The interaction of HIVEN86A, and presumably other cellular proteins, with the HIV-1 enhancer appears functionally important as oligonucleotides corresponding to this enhancer were sufficient to impart Tax inducibility to an unresponsive heterologous promoter. These findings suggest that the Tax-inducible cellular protein HIVEN86A plays an important role in the transcriptional activation of the HIV-1 enhancer. These specific protein-DNA interactions may also be important for the transition of HIV-1 from a latent to a productive mode of infection. Furthermore, these findings highlight an intriguing biological interplay between HTLV-1 and HIV-1 through a cellular transcriptional pathway that is normally involved in T-cell activation and growth.
authors: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
authors: E
authors: E
authors: Böhnlein
authors: M
authors: M
authors: Siekevitz
authors: D W
authors: DW
authors: Ballard
authors: J W
authors: JW
authors: Lowenthal
authors: L
authors: L
authors: Rimsky
authors: H
authors: H
authors: Bogérd
authors: J
authors: J
authors: Hoffman
authors: Y
authors: Y
authors: Wano
authors: B R
authors: BR
authors: Franza
authors: W C
authors: WC
authors: Greene
mesh_terms: D002460:Cell Line; D004252:DNA Mutational Analysis; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006678:HIV / Q000235:genetics*; D015486:HTLV-I Antigens / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008970:Molecular Weight; D011401:Promoter Regions, Genetic; D012191:Retroviridae Proteins / Q000502:physiology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D015486:HTLV-I Antigens; D012191:Retroviridae Proteins; D015534:Trans-Activators; D014157:Transcription Factors