INHIBITION OF HIV-1-INDUCED SYNCYTIA FORMATION AND INFECTIVITY BY LIPOPHOSPHOGLYCAN FROM LEISHMANIA

In HIV-1 infection, the appearance of syncytia-inducing (SI) isolates is associated with a more rapid decline of CD4(+) cells and progressio n to AIDS. Agents that inhibit either virus infection or syncytia form ation have the potential to be therapeutically useful. Lipophosphoglyc an (LPG), the major glycoconjugate of Leishmania, was recently shown t o be a potent nonspecific inhibitor of viral membrane fusion. In this study, LPG demonstrated a dose-dependent inhibition of HIV-1-induced s yncytia formation in CD4(+) MT-2 cells infected with distinct SI isola tes. Fragments of LPG were used to show that inhibition of syncytia fo rmation 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 mon onuclear cells at the highest concentrations used in these assays. Fur ther, LPG rapidly associated with the surface membrane of a human T ce ll line and subsequently disassociated over a 24-h period. The develop ment of compounds capable of inhibiting HIV-induced syncytia formation should provide novel therapeutic approaches to control the spread of virus and disease progression.