       Document 0229
 DOCN  M9620229
 TI    Coexpression of NF-kappa B/Rel and Sp1 transcription factors in human
       immunodeficiency virus 1-induced, dendritic cell-T-cell syncytia.
 DT    9602
 AU    Granelli-Piperno A; Pope M; Inaba K; Steinman RM; Laboratory of Cellular
       Physiology and Immunology, Rockefeller; University, New York, NY 10021,
       USA.
 SO    Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):10944-8. Unique Identifier
       : AIDSLINE MED/96074623
 AB    Productive infection of T cells with human immunodeficiency virus 1
       (HIV-1) typically requires that the T cells be stimulated with antigens
       or mitogens. This requirement has been attributed to the activation of
       the transcription factor NF-kappa B, which synergizes with the
       constitutive transcription factor Sp1 to drive the HIV-1 promoter.
       Recently, we have found that vigorous replication of HIV-1 takes place
       in nonactivated memory T cells after syncytium formation with dendritic
       cells (DCs). These syncytia lack activated cells as determined by an
       absence of staining for Ki-67 cell cycle antigen. The expression and
       activity of NF-kappa B and Sp1 were, therefore, analyzed in isolated T
       cells and DCs from humans and mice. We have used immunolabeling, Western
       blot analysis, and electrophoretic mobility shift and supershift assays.
       T cells lack active NF-kappa B but express Sp1 as expected. DCs express
       high levels of all known NF-kappa B and Rel proteins, with activity
       residing primarily within RelB, p50, and p65. However, DCs lack Sp1,
       which may explain the failure of HIV-1 to replicate in purified DCs.
       Coexpression of NF-kappa B and Sp1 occurs in the heterologous DC-T-cell
       syncytia that are induced by HIV-1. Therefore, HIV-1-induced cell fusion
       brings together factors that upregulate virus transcription. Since DCs
       and memory T cells frequently traffic together in situ, these unusual
       heterologous syncytia could develop in infected individuals and lead to
       chronic HIV-1 replication without ostensible immune stimulation.
 DE    Animal  Base Sequence  Cells, Cultured  Dendritic
       Cells/CYTOLOGY/*METABOLISM/MICROBIOLOGY  Gene Expression Regulation,
       Viral  Giant Cells/*METABOLISM  Hela Cells  Human  HIV
       Infections/*METABOLISM  HIV-1/GROWTH & DEVELOPMENT  Mice  Molecular
       Sequence Data  NF-kappa B/*METABOLISM
       Oligodeoxyribonucleotides/CHEMISTRY  Promoter Regions (Genetics)
       Proto-Oncogene Proteins/*METABOLISM  RNA, Messenger/GENETICS
       Skin/CYTOLOGY/METABOLISM  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  T-Lymphocytes/*METABOLISM/MICROBIOLOGY  Transcription Factor,
       Sp1/*METABOLISM  Virus Replication  JOURNAL ARTICLE

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

