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1996-02-26
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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).