Characterization of lectin-mediated brain uptake of HIV-1 GP120.
The viral coat of the HIV-1 virus, gp120, has been shown to cross the blood-brain barrier (BBB) in lectin-like fashion by inducing adsorptive endocytosis (AE), a vesicular mechanism that could provide pathways into and across brain endothelial cells for virus and infected immune cells. Here, we extended those findings to show that gp120 slowly crossed the BBB with about 0.15% of an intravenously injected dose entering the brain after about 2 hr. The plant lectin glycoprotein wheat germ agglutinin (WGA) greatly enhanced gp120 crossing without disrupting the BBB. WGA enhanced the uptake of gp120 into all peripheral tissues studied, but the greatest percent increase occurred for brain, whereas another barrier tissue, the testis, had the least increase. Five other plant lectins tested had little or no effect on gp120 uptake by brain, suggesting a key role for sialic acid and N-acetyl-beta-D-glucosaminyl acid, the sugars to which WGA binds, in the uptake of gp120 by brain endothelial cells. WGA did not enhance the uptake of nonglycosylated gp120 and the uptake of gp120 was not self-inhibitable or altered by pretreatment of mice with aluminum. In conclusion, these studies show that gp120 crosses the BBB by a lectin-like mechanism resembling AE that is likely mediated by binding to specific sugar moieties and is rather selective for brain.
Banks
W A
WA
GRECC, Veterans Affairs Medical Center-St. Louis, Department of Internal Medicine, Saint Louis University School of Medicine, Missouri, USA.
Kastin
A J
AJ
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000097:blood / Q000378:metabolism*; D006207:Half-Life; D007275:Injections, Intravenous; D007700:Kinetics; D037102:Lectins / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010539:Permeability / Q000187:drug effects; D010949:Plasma; D012276:Ricin / Q000494:pharmacology; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D014909:Wheat Germ Agglutinins / Q000494:pharmacology
D015699:HIV Envelope Protein gp120; D037102:Lectins; D014909:Wheat Germ Agglutinins; D012276:Ricin