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-1), they lack CD4, galactoceramides (GalCer) and sulfogalactoceramides (SGalCer) as gp120 receptors. However, sperm specific glycolipids (sulfogalactosylalkylacylglycerol (SGalAAG) and galactosylalkylacylglycerol (GalAAG)) are structurally closely related to SGalCer and GalCer as predicted by computer simulated molecular modelling. SGalAAG and GalAAG are exclusively localized in the outer leaflet of the human sperm plasma membrane, and therefore we tested whether they could serve as alternative receptors for the gp120. Purified SGalAAG and GalAAG had similar affinities to recombinant gp120 as the hydroxy fatty acid (HFA) SGalCer and HFA-GalCer respectively. However, nonhydroxy fatty acid forms of (S)GalCer, galactosyldiacylglycerol and the deacylated (sulfo)galactosyllipids did not recognize recombinant gp120. Data obtained by surface pressure experiments revealed that the lipid monolayers that contained HFA-GalCer or GalAAG resulted in a similar significant penetration of recombinant gp120 in the monolayer. The penetration was a factor of two lower in monolayers with HFA-SGalCer or SGalAAG. The binding of recombinant gp120 to human sperm cells colocalized with GalAAG and could be blocked with monoclonal antibodies against galactolipids. The possible relevance of gp120 binding to glycolipids for HIV entry in sperm cells is discussed.
Gadella
B M
BM
Department of Herd Health and Reproduction, Faculty of Veterinary Medicine, Graduate School of Animal Health, Utrecht University, The Netherlands. B.Gadella@biochem.dgk.ruu.nl
Hammache
D
D
Piéroni
G
G
Colenbrander
B
B
van Golde
L M
LM
Fantini
J
J
D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D006017:Glycolipids / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008297:Male; D008561:Membrane Fusion / Q000502:physiology*; D015728:Receptors, HIV / Q000378:metabolism*; D013094:Spermatozoa / Q000378:metabolism / Q000821:virology*
D006017:Glycolipids; D015699:HIV Envelope Protein gp120; D015728:Receptors, HIV; C009233:seminolipid