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Inhibition of HIV-1-Induced Syncytia Formation and Infectivity by Lipophosphoglycan from Leishmania

Easterbrook, Mark D.; Levy, Michelle H.; Gomez, Ana M.; Turco, Salvatore J.; Epand, Richard M.; Rosenthal, Kenneth L.
JAIDS Journal of Acquired Immune Deficiency Syndromes: December 5th, 1995
BASIC SCIENCE: PDF Only

Summary: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 dosedependent 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.

Molecular Virology and Immunology Programme, Departments of Pathology and *Biochemistry, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada; and †Department of Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky, U.S.A.

Address correspondence and reprint requests to Dr. K. L. Rosenthal at Molecular Virology and Immunology Programme, Department of Pathology, McMaster University Health Sciences Centre, 1200 Main St. W., Hamilton, Ontario, Canada L8N 3Z5.

Manuscript received August 31, 1994; accepted June 11, 1995.

© Lippincott-Raven Publishers.