       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).

