ADSORPTIVE ENDOCYTOSIS MEDIATES THE PASSAGE OF HIV-1 ACROSS THE BLOOD-BRAIN-BARRIER - EVIDENCE FOR A POST-INTERNALIZATION CORECEPTOR

HIV-1 induces the AIDS dementia complex and infects brain endothelial and glial cells. Because the endothelial cells comprising the blood-br ain barrier (BBB) do not possess CD4 receptors or galactosylceramide b inding sites, it is unclear how HIV-1 negotiates the BBB, Previous wor k has suggested that gp120, the glycoprotein viral coat of HIV-1, is c apable of inducing adsorptive endocytosis. Glycoprotein lectins like w heatgerm agglutinin induce adsorptive endocytosis and greatly potentia te the uptake by and passage across mouse endothelial cells in vivo an d in vitro. We show here that the wheatgerm agglutinin-induced binding of gp120 is dose-dependent and involves components of the cytoskeleto n, The uptake is partially dependent on temperature and energy and is modestly enhanced by potassium depletion. Glycosylation of gp120 is cr itical for its uptake by adsorptive endocytosis since the non-glycosyl ated form of gp120 is unaffected by wheatgerm agglutinin. Evidence is presented for the existence of a coreceptor sensitive to protamine sul fate that is primarily involved in membrane fusion after I-125-gp120 h as bound to the cell membrane and is probably activated after internal ization. This coreceptor probably contains a negatively charged hepari n sulfate group and could be a member of the chemokine receptor family .