Glycolipids as potential binding sites for HIV: topology in the sperm plasma membrane in relation to the regulation of membrane fusion

Although human sperm cells can bind human immunodeficiency virus (HIV-I), t hey lack CD4, galactoceramides (GalCer) and sulfogalactoceramides (SGalCer) as gp120 receptors. However, sperm specific glycolipids (sulfogalactosylal kylacylglycerol (SGalAAG) and galactosylalkylacylglycerol (GalAAG)) are str ucturally closely related to SGalCer and GalCer as predicted by computer si mulated molecular modelling. SGalAAG and GalAAG are exclusively localized i n the outer leaflet of the human sperm plasma membrane, and therefore we te sted whether they could serve as alternative receptors for the gp120. Purif ied SGalAAG and GalAAG had similar affinities to recombinant gp120 as the h ydroxy fatty acid (HFA) SGalCer and HFA-GalCer respectively. However, nonhy droxy fatty acid forms of (S)GalCer, galactosyldiacylglycerol and the deacy lated (sulfo)galactosyllipids did not recognize recombinant gp120. Data obt ained by surface pressure experiments revealed that the lipid monolayers th at contained HFA-GalCer or GalAAG resulted in a similar significant penetra tion of recombinant gp120 in the monolayer. The penetration was a factor of two lower in monolayers with HFA-SGalCer or SGalAAG. The binding of recomb inant gp120 to human sperm cells colocalized with GalAAG and could be block ed with monoclonal antibodies against galactolipids. The possible relevance of gp120 binding to glycolipids for HIV entry in sperm cells is discussed. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.