MEMBRANE-INTERACTIVE PHOSPHOLIPIDS INHIBIT HIV TYPE 1-INDUCED CELL-FUSION AND SURFACE GP160 GP120 BINDING TO MONOCLONAL-ANTIBODY/

Membrane-interactive phospholipids (PLs), previously evaluated for act ivity against HIV-1 in vitro, are known to affect late steps in viral replication. Studies were done to determine the effects of PL analogs on posttranslational processing of HIV-1 proteins, binding of viral su rface gp160/gp120 to CD4 receptor, and HIV-1-induced cell fusion. Resu lts of this investigation indicated that PL alone ctadecanamido-2-etho xypropyl-rac-3-phosphocholine, CP-51) and PL-AZT conjugate xypropyl-ra c-3-phospho-3'-azido-3'-deoxythymidine, CP-92) have no effect on HIV-1 -induced syntheses or processing of gp160/gp120, pr51, p24, or p17 (in cluding myristoylation) in infected cells. Progeny HIV-1 particles mad e in CP-92-treated H9IIIB cells contained gp120, pr51, and p24; howeve r, these virus particles had reduced capacity to bind to CD4(+) cells. Both CP-51 and CP-92 inhibited syncytium (cell fusion) formation betw een treated HIV-1-infected cells and uninfected CD4(+) cells, and, the y reduced HIV-1 gp160/gp120 binding to CD4(+) cells and monoclonal ant ibody. These results suggest that anti-HIV-1 activity of PL compounds involves alteration of cell surface membranes and viral envelopes. Pho spholipid compounds are a novel class of membrane interactive compound s with potential use in blocking the spread of HIV-1 infection and pat hogenesis in AIDS.