Human erythrocyte glycosphingolipids as alternative cofactors for human immunodeficiency virus type 1 (HIV-1) entry: Evidence for CD4-Induced interactions between HIV-1 gp120 and reconstituted membrane microdomains of glycosphingolipids (gb3 and GM3)

Glycosphingolipids from human erythrocytes mediate CD4-dependent fusion wit h cells expressing human immunodeficiency virus type 1 (HIV-1) envelope gly coproteins. To identify the glycosphingolipid(s) which participates in the fusion process, we have analyzed the interaction of HIV-1 gp120 (X4 and R5X 4 isolates) with reconstituted membrane microdomains of human erythrocyte g lycosphingolipids. We identified globotriaosylceramide (Gb3) and gangliosid e GM3 as the main glycosphingolipids recognized by gp120. In the presence o f CD4, Gb3 interacted preferentially with the X4 gp120, whereas GM3 interac ted exclusively with the R5X4 gp120. These data suggest that glycosphingoli pid microdomains are required in CD4-dependent fusion and that Gb3 and/or G M3 may function as alternative entry cofactors for selected HIV-1 isolates.