The fusion domain of HIV gp41 interacts specifically with heparan sulfate on the T-lymphocyte cell surface.
Studies of the interaction of the 16 residue fusion peptide domain of human immunodeficiency virus glycoprotein gp41 (gp41(FD)) with T lymphocytes are outlined. Fluorescence measurements of changes in the electrostatic surface and dipole potentials of the plasma membrane following the interaction with gp41(FD) are described. The results show that gp41(FD) interacts with heparan sulfate located on the cell surface. This interaction is blocked by interleukin-8 and abolished by pre-treating the cells with heparitinase. The specificity of the reaction was also assessed by observations that soluble heparan sulfate competes with the cell membrane interaction whereas soluble heparin (at the levels utilized) does not. Following binding to heparan sulfate, the interaction with the membrane seems to take place in a cooperative manner with the formation of gp41(FD) trimers. In simpler phospholipid membranes, however, a trimeric complex does not appear to be the dominant mode of interaction. Finally, by repeating some of these studies within an imaging regime, it appears that the gp41(FD)-T-cell interaction takes place within specific domains on the cell surface to similarly localized heparan sulfate moieties.
School of BioMedical Sciences, University of Nottingham, Nottingham NG7 2UH, UK.
J
J
Cladera
I
I
Martin
P
P
O'Shea
D001665:Binding Sites; D002462:Cell Membrane / Q000502:physiology / Q000821:virology; D006678:HIV / Q000187:drug effects / Q000502:physiology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D019169:Jurkat Cells; D007700:Kinetics; D008561:Membrane Fusion / Q000187:drug effects; D018613:Microscopy, Confocal; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D055672:Static Electricity; D013601:T-Lymphocytes / Q000502:physiology* / Q000821:virology*
D015700:HIV Envelope Protein gp41; D006497:Heparan Sulfate; D016209:Interleukin-8; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase