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1996-03-04
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Document 0763
DOCN M9640763
TI Inhibition of HIV-1-induced syncytia formation and infectivity by
lipophosphoglycan from Leishmania.
DT 9604
AU Easterbrook MD; Levy MH; Gomez AM; Turco SJ; Epand RM; Rosenthal KL;
Department of Pathology, McMaster University Health Sciences; Centre,
Hamilton, Ontario, Canada.
SO J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Dec 15;10(5):496-505.
Unique Identifier : AIDSLINE MED/96142211
AB In HIV-1 infection, the appearance of syncytia-inducing (SI) isolates is
associated with a more rapid decline of CD4+ cells and progression to
AIDS. Agents that inhibit either virus infection or syncytia formation
have the potential to be therapeutically useful. Lipophosphoglycan
(LPG), the major glycoconjugate of Leishmania, was recently shown to be
a potent nonspecific inhibitor of viral membrane fusion. In this study,
LPG demonstrated a dose-dependent inhibition of HIV-1-induced syncytia
formation in CD4+ MT-2 cells infected with distinct SI isolates.
Fragments of LPG were used to show that inhibition of syncytia formation
was dependent on the length of the LPG fragment. Treatment of CD4+ cells
or HIV-1 isolates with LPG inhibited infection in vitro. Furthermore,
LPG inhibited the replication of SI viral isolates in CD4+ T cells in
vitro. LPG had no toxic effects on peripheral blood mononuclear cells at
the highest concentrations used in these assays. Further, LPG rapidly
associated with the surface membrane of a human T cell line and
subsequently disassociated over a 24-h period. The development of
compounds capable of inhibiting HIV-induced syncytia formation should
provide novel therapeutic approaches to control the spread of virus and
disease progression.
DE Animal Cell Division/DRUG EFFECTS Cell Fusion/*DRUG EFFECTS Cell
Membrane/DRUG EFFECTS Cells, Cultured CD4-Positive T-Lymphocytes/DRUG
EFFECTS/*VIROLOGY Dose-Response Relationship, Drug Giant Cells/DRUG
EFFECTS/VIROLOGY Glycosphingolipids/ISOLATION &
PURIF/*PHARMACOLOGY/TOXICITY Human HIV-1/*DRUG EFFECTS/PHYSIOLOGY
Leishmania donovani/*CHEMISTRY Leishmania major/*CHEMISTRY Leukocytes,
Mononuclear/DRUG EFFECTS Support, Non-U.S. Gov't Virus
Replication/DRUG EFFECTS JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).