Evidence that mannosyl residues are involved in human immunodeficiency virus type 1 (HIV-1) pathogenesis.
The Human Immunodeficiency Virus (HIV), the causative agent of AIDS, is thought to bind to T4+ (CD4+) target cells through the heavily glycosylated gp120 envelope glycoprotein. Plant lectins bind glycoproteins through noncovalent interaction with specific hexose residues; therefore, lectins were evaluated for their ability to inactivate HIV in vitro. The mannose-specific lectins concanavalin-A and succinyl concanavalin-A completely inactivated HIV while lentil lectin, wheat germ agglutinin, and phytohemagglutinin-P substantially inactivated HIV. BS-II, Vicia villosa (hairy vetch), and Ptilota plumosa (red marine algae) failed to alter the infectibility of HIV. Neither simple stearic hindrance, viral aggregation, nor lectin-cell interactions served to explain this phenomenon. Glycoprotein glycosylation was evaluated by differential lectin binding as well as molecular weight changes in gp120 when virus was produced in the presence of swainsonine, a glycosylation inhibitor. Lentil lectin bound gp120 better than concanavalin-A, suggesting the majority of glycosylation sites are fucosylated. The apparent molecular weight of gp120 was reduced by swainsonine, although HIV infectivity and concanavalin-A inactivation were retained. Thus, at least some N-glycosylation sites are complex-type glycoproteins but regions external to the (GlcNAc)2(Man)3 "core" pentasaccharide region are not required for HIV infectivity. It appears that the site or sites involved are nonfucosylated, high mannose and/or biantennary, nonsialylated, N-glycosylated regions of gp120 or gp41. Alternatively, they may be in close approximation to such carbohydrate regions.
Robinson
W E
WE
Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Montefiori
D C
DC
Mitchell
W M
WM
D000470:Alkaloids / Q000494:pharmacology; D001665:Binding Sites; D006031:Glycosylation; D006678:HIV / Q000187:drug effects / Q000472:pathogenicity*; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D037102:Lectins / Q000494:pharmacology*; D008358:Mannose / Q000502:physiology*; D012191:Retroviridae Proteins / Q000378:metabolism; D017026:Swainsonine; D014759:Viral Envelope Proteins / Q000378:metabolism
D000470:Alkaloids; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D037102:Lectins; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins; D008358:Mannose; D017026:Swainsonine