Human erythrocyte glycolipids promote HIV-1 envelope glycoprotein-mediated fusion of CD4+ cells

We examined the role of target membrane glycolipids in CD4-mediated HIV-1 fusion by altering the glycolipid levels in CD4(+) cells. CD4(+) human cells exhibited 50% reduction in extent of fusion with gp120-gp41 expressing cells (TF228) when grown in the presence of a glycolipid synthesis inhibitor PPMP. We added erythrocyte glycolipids (GL) to fusion-incompetent CD4(+) non-human cells by influenza-hemagglutinin-mediated fusion between GL-containing liposomes and target cells. Human erythrocyte GL (HuGL)-modified CD4(+) non-human cells became susceptible to fusion with TF228 cells. Transfer of bovine erythrocyte glycolipids (BoGL) to CD4(+) non-human cells under similar conditions did not complement HIV-1 fusion, Furthermore, addition of HuGL, but not BoGL, to PPMP-inhibited cells rescued fusion to the original levels. Our observations demonstrate that human erythrocyte glycolipids promote CD4-mediated HIV-1 fusion and certain glycolipid(s) from human erythrocytes may serve as alternative and/or additional cofactors in HIV-1 entry. (C) 1998 Academic Press.