HIV-INFECTION OF HUMAN FETAL NEURAL CELLS IS MEDIATED BY GP120 BINDING TO A CELL MEMBRANE-ASSOCIATED MOLECULE THAT IS NOT CD4 NOR GALACTOCEREBROSIDE

HIV infection of central nervous system (CNS) tissue is a common findi ng in both adult and pediatric AIDS. Because most children are believe d to be infected perinatally, we have developed a model of HIV CNS inf ection that utilizes explant organotypic cultures of human fetal CNS t issue. Using this model we previously reported that both lymphocytotro pic and monocytotropic HIV isolates infect microglia and astrocytes. H owever, the mechanism by which HIV infects these cells remains to be e lucidated. We have observed that neural cell infection in these cultur es may be the result of receptor-mediated endocytosis. In order to con firm this observation and to determine the ligand responsible for this process, organotypic cultures were exposed to untreated HIV, HIV pret reated with soluble CD4 (sCD4) or, as a control, heat-inactivated HIV. To address the question of a putative receptor for HIV infection, CNS cultures were either untreated or pretreated with gp120 or with the d eglycosylated form of this protein. Other cultures were treated with a ntibodies to CD4 (anti-T4A) or to galactocerebroside (GC). Results dem onstrate that pretreatment of either HIV with sCD4 or CNS cultures wit h gp120 significantly inhibits HIV infection. The inhibition of infect ion was demonstrated by a reduction in the number of cells positive fo r HIV proteins and by decreases in HIV proviral DNA and p24 production . Pretreatment of CNS cultures with deglycosylated gp120, anti-T4A or anti-GC antibodies did not inhibit HIV infection. These data suggest t hat HIV gp120 is needed for binding to a surface molecule on CNS cells that is not CD4 nor GC and that this molecule may function as a recep tor and lead to infection of neural cells. (C) 1997 Elsevier Science B .V.