A murine IgG mAb WR321 selected for the ability to bind to phosphatidylinositol-4-phosphate and phosphatidylinositol-4 5-bisphosphate but an inability to bind to any of 17 other lipids including phosphatidylinositol was examined as a probe for studying interactions of HIV-1 with primary human peripheral blood mononuclear cells The WR321 mAb broadly neutralized CCR5 tropic strains of HIV-1 to prevent infection of the cells The mAb also exhibited direct interaction with cells in the culture resulting in secretion of chemokines that interfered with the interaction of HIV-1 virions with CCR5 the coreceptor for HIV-1 on the susceptible cells leading to inhibition of infection by HIV-1 Phosphoinositides that are recognized by WR321 do not exist on the external surface of cells but are concentrated on the inner surface (cytoplasmic leaflet) of the plasma membrane Murine anti-phosphoinositide mAbs similar to WR321 have previously been directly microinjected Into a variety of cultured cells resulting in important changes in the functions of the cells The present results suggest that binding of a mAb to phosphoinositides resulting in secretion of beta-chemokines into the culture medium and neutralization of infection by CCR5-tropic HIV-1 of nearby susceptible cells occurred by uptake and binding of the mAb at an intracellular location in the cultured cells that then led to secretion of HIV-1-inhibitory beta-chemokines Published by Elsevier Inc