       Document 0118
 DOCN  M9580118
 TI    Absolute dependence on kappa B responsive elements for initiation and
       Tat-mediated amplification of HIV transcription in blood CD4 T
       lymphocytes.
 DT    9506
 AU    Alcami J; Lain de Lera T; Folgueira L; Pedraza MA; Jacque JM; Bachelerie
       F; Noriega AR; Hay RT; Harrich D; Gaynor RB; et al; Servicio de
       Microbiologia, Hospital 12 de Octubre, Madrid,; Spain.
 SO    EMBO J. 1995 Apr 3;14(7):1552-60. Unique Identifier : AIDSLINE
       MED/95246748
 AB    The role of NF-kappa B-dependent signals in activating the
       transcriptional activity of the HIV regulatory region (LTR) was analyzed
       by systematic comparison of HIV LTR activity in human CD4 T cells
       purified from peripheral blood and a transformed lymphoblastoid T cell
       line. In normal CD4 T cells we also analyzed the role played by the
       viral kappa B responsive elements in HIV replication. Analysis of
       nuclear extracts of resting, normal T lymphocytes revealed the presence
       of the p50, but not the p65, NF-kappa B subunit and the induction by
       phorbol esters of bona fide (p50-p65) NF-kappa B complexes. In parallel,
       we observed clear enhancer-dependent HIV LTR transactivation comparable
       in intensity with that observed in lymphoblastoid cells. We show that
       unstimulated CD4 T lymphocytes offer a cellular environment of very low
       permissivity to HIV LTR functioning. This was in sharp contrast to the
       high spontaneous LTR activity observed in lymphoblastoid T cells, where
       LTR activity was essentially independent of kappa B-responsive elements.
       Due to the low basal LTR activity in resting T lymphocytes, NF-kappa
       B-dependent transactivation was a sine qua non event for induction of
       the HIV LTR. Surprisingly, even the function of HIV Tat in resting CD4 T
       lymphocytes was found to be absolutely dependent on LTR kappa B
       responsive elements. The relevance of these observations obtained in
       transient transfections was confirmed by the incapacity of blood CD4 T
       lymphocytes infected with an HIV infectious provirus carrying critical
       point mutations in the kappa B responsive elements to show any
       detectable transcriptional activity upon cell activation and prolonged
       culture in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Base Sequence  Cell Line, Transformed  Cells, Cultured  Comparative
       Study  CD4-Positive T-Lymphocytes/PHYSIOLOGY/*VIROLOGY  DNA,
       Viral/BIOSYNTHESIS  Enhancer Elements (Genetics)  *Gene Expression
       Regulation, Viral  Gene Products, tat/BIOSYNTHESIS/*METABOLISM  Human
       HIV/*GENETICS/*METABOLISM  Kinetics  Molecular Sequence Data  NF-kappa
       B/*METABOLISM  Proviruses/GENETICS/PHYSIOLOGY  RNA,
       Messenger/BIOSYNTHESIS  RNA, Viral/BIOSYNTHESIS  Signal Transduction
       Support, Non-U.S. Gov't  T-Lymphocytes/PHYSIOLOGY/*VIROLOGY
       Transcription, Genetic  Transfection  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

