Specific Interaction of HIV-1 and HIV-2 Surface Envelope Glycoproteins with Monolayers of Galactosylceramide and Ganglioside GM3

Abstract

Cellular glycosphingolipids mediate the fusion between some viruses and the plasma membrane of target cells. In the present study, we have analyzed the interaction of human immunodeficiency virus (HIV)-1 and HIV-2 surface envelope glycoproteins from distinct viral isolates with monolayers of various glycosphingolipids at the air-water interface. The penetration of the viral glycoproteins into glycosphingolipid monolayers was detected as an increase in the surface pressure. We found that HIV-1 recombinant gp120 (IIIB isolate) could penetrate into a monomolecular film of ␣-hydroxylated galactosylceramide (GalCer-HFA), while ceramides, GluCer, and nonhydroxylated GalCer were totally inactive. The glycoproteins isolated from HIV-1 isolates LAI and NDK and from HIV-2(ROD) could also interact with a GalCer-HFA monolayer, whereas gp120 from HIV-1(SEN) and HIV-1(89.6) did not react. These data correlated with the ability of the corresponding viruses to gain entry into the CD4 ؊ /GalCer ؉ cell line HT-29, demonstrating the determinant role of GalCer-HFA in this CD4-independent pathway of HIV-1 and HIV-2 infection. In contrast, all HIV-1 and HIV-2 glycoproteins tested were found to interact with a monolayer of GM3, a ganglioside abundantly expressed in the plasma membrane of CD4 ؉ lymphocytes and macrophages. A V3 loop-derived synthetic peptide inhibitor of HIV-1 and HIV-2 infection in both CD4؊ and CD4 ؉ cells could penetrate into various glycosphingolipid monolayers, including GalCer-HFA and GM3. Taken together, these data suggest that the adsorption of human immunodeficiency viruses to the surface of target cells involves an interaction between the V3 domain of the surface envelope glycoprotein and specific glycosphingolipids, i.e. GalCer-HFA for CD4 ؊ cells and GM3 for CD4 ؉ cells.

Inefficient fusion due to a lack of attachment receptor/co-receptor restricts productive human immunodeficiency virus type 1 infection in human hepatoma Huh7.5 cells

“…One of them, GalCer was described previously as an HIV-1 alternate receptor on neural cell lines (Harouse et al, 1991) and also on human colon epithelial cells (Yahi et al, 1992). The propensity of the NDK isolate to infect CD4-negative epithelial cells through the GalCer cell surface constituent was confirmed in another study (Hammache et al, 1998). In order to determine if this CD4-independent infection process can ensue in Huh7.5 cells, we first assessed surface expression of GalCer by flow cytometry.…”

HIV-1 incorporation of host-cell–derived glycosphingolipid GM3 allows for capture by mature dendritic cells

“…On the basis of the capture profiles, we predicted that only the GM3-and GM1-enriched liposomes would competitively inhibit virus capture by mDCs. HIV-1 Env is known to bind GM3 (19); therefore, HIV Lai devoid of glycoprotein (HIV Lai ΔEnv) and Gag-eGFP VLPs were used in these assays. Mature DCs were first treated with 0.1% sodium azide (NaN 3 ) to prevent membrane recycling and internalization of the liposome.…”

Identification of a Common Sphingolipid-binding Domain in Alzheimer, Prion, and HIV-1 Proteins

“…Correspondingly, infectious prion rods were found to contain the two sphingolipids galactosylceramide (GalCer) and sphingomyelin, suggesting that both lipids may interact with normal and/or pathogenic prion proteins (4). Interestingly, the HIV-1 surface envelope glycoprotein gp120 also interacts with GalCer (5,6), as well as with a few other sphingolipids found in membrane rafts, i.e. the ceramide trihexoside Gb3, the monosialoganglioside GM3, and sphingomyelin (6 -10).…”