HIV infection of fetal human astrocytes: the potential role of a receptor-mediated endocytic pathway

HIV infects microglia and astrocytes both in vivo and in vitro. Although th ere is a significant amount of information about microglial infection, data regarding astrocytes are more limited. For example, little is known about the initial membrane events occurring between HIV and astrocytes. Also, the mechanism by which HIV enters these cells remains to be determined. To add ress these questions, we exposed human astrocyte cultures to either HIV or to the HIV glycoprotein gp120. The cultures were analyzed for viral infecti on and gp120 binding to cultured cells by light and electron microscopy (EM ) with and without immunocytochemistry, respectively; ligand-receptor bioch emistry; and, Western, Northern and Southern blot analyses. The results of these studies showed that HIV binds to astrocytes via gp120 and a cell surf ace molecule weighing approximately 65 kDa that is neither CD4 nor galactoc erebroside. Furthermore, binding or gp120 to astrocytes was concentration d ependent and displayed a curve consistent with ligand-receptor binding. Add itionally, radiolabeled gp120 binding was displaced by unlabeled gp120 but not by deglycosylated gp120, suggesting that the binding was specific. By E M, HIV virions were seen in clathrin-coated pits and in cytoplasmic vacuole s. This suggests linkage, in astrocytes, between a plasma membrane-associat ed protein that can act as a receptor for HN and an endosomal pathway. (C) 1999 Elsevier Science B.V. All rights resented.