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1996-02-26
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Document 0529
DOCN M9620529
TI Triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18)
induces nuclear translocation of NF-kappa B (p50/p65) in human monocytes
and enhances viral replication in HIV-infected monocytic cells.
DT 9602
AU Thieblemont N; Haeffner-Cavaillon N; Haeffner A; Cholley B; Weiss L;
Kazatchkine MD; INSERM U430, Broussais Hospital, Paris, France.
SO J Immunol. 1995 Nov 15;155(10):4861-7. Unique Identifier : AIDSLINE
MED/96062305
AB Monocyte/macrophages may harbor HIV in a nonproductive fashion for
prolonged periods of time. Viral gene expression may be reactivated by
stimulation of the cells with LPS or cytokines such as TNF-alpha in
vitro. The effect of LPS and TNF-alpha is mediated by their ability to
induce nuclear translocation of the DNA-binding heterodimer NF-kappa B
(p50/p65), which binds to a specific sequence in the HIV-long terminal
repeat. The present study demonstrates that triggering of complement
receptors CR1 (CD35) and CR3 (CD11b/CD18) enhances viral replication in
HIV-infected human monocytic cells. Monocytic cell lines and normal
peripheral blood monocytes were infected with HIV-1 in vitro and
cultured in the presence or absence of F(ab')2 fragments of monoclonal
anti-CR1 or anti-CR3 Abs or with C3 fragments. Stimulation of CR1 or CR3
induces a two- to fourfold increase in the amount of cell-associated and
released p24 Ag in cell cultures that was equivalent to that observed in
control cultures triggered with LPS. We further observed that
stimulation of CR1 or CR3 induces the nuclear translocation of NF-kappa
B p50/p65 in infected cells. Translocation of NF-kappa B p50/p65 was
also observed following stimulation of CR1 or CR3 of uninfected
peripheral blood monocytes from HIV-seronegative donors. The amount of
protein translocated was similar to that observed when cells were
stimulated with rhTNF-alpha. TNF-alpha did not mediate the translocation
of NF-kappa B p50/p65 induced by triggering of complement receptors.
Taken together, these observations suggest that HIV gene expression may
be activated in infected monocytes through interaction of the cells with
complement-opsonized particles and that enhanced viral replication is
associated with C3 receptor-mediated nuclear translocation of the
NF-kappa B complex.
DE Antigens, CD11/*PHYSIOLOGY Biological Transport Cell
Nucleus/PHYSIOLOGY Cells, Cultured *DNA Replication Human HIV
Infections/IMMUNOLOGY/*PHYSIOPATHOLOGY HIV-1/*PHYSIOLOGY
Monocytes/PHYSIOLOGY/*VIROLOGY NF-kappa B/*PHYSIOLOGY Receptors,
Complement 3b/*PHYSIOLOGY Support, Non-U.S. Gov't *Virus Replication
JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).