title: Host-soluble galectin-1 promotes HIV-1 replication through a direct interaction with glycans of viral gp120 and host CD4.
abstract: Sexual transmission of HIV-1 requires virus adsorption to a target cell, typically a CD4(+) T lymphocyte residing in the lamina propria, beneath the epithelium. To escape the mucosal clearance system and reach its target cells, HIV-1 has evolved strategies to circumvent deleterious host factors. Galectin-1, a soluble lectin found in the underlayers of the epithelium, increases HIV-1 infectivity by accelerating its binding to susceptible cells. By comparison, galectin-3, a family member expressed by epithelial cells and part of the mucosal clearance system, does not perform similarly. We show here that galectin-1 directly binds to HIV-1 in a β-galactoside-dependent fashion through recognition of clusters of N-linked glycans on the viral envelope gp120. Unexpectedly, this preferential binding of galectin-1 does not rely on the primary sequence of any particular glycans. Instead, glycan clustering arising from the tertiary structure of gp120 hinders its binding by galectin-3. Increased polyvalency of a specific ligand epitope is a common strategy for glycans to increase their avidity for lectins. In this peculiar occurrence, glycan clustering is instead exploited to prevent binding of gp120 by galectin-3, which would lead to a biological dead-end for the virus. Our data also suggest that galectin-1 binds preferentially to CD4, the host receptor for gp120. Together, these results suggest that HIV-1 exploits galectin-1 to enhance gp120-CD4 interactions, thereby promoting virus attachment and infection events. Since viral adhesion is a rate-limiting step for HIV-1 entry, modulation of the gp120 interaction with galectin-1 could thus represent a novel approach for the prevention of HIV-1 transmission.
authors: Glycobiology and Bioimaging Laboratory, Faculty of Medicine, Laval University, 2705 Boul. Laurier, Quebec G1V 4G2, Canada.
authors: Christian
authors: C
authors: St-Pierre
authors: Hiroshi
authors: H
authors: Manya
authors: Michel
authors: M
authors: Ouellet
authors: Gary F
authors: GF
authors: Clark
authors: Tamao
authors: T
authors: Endo
authors: Michel J
authors: MJ
authors: Tremblay
authors: Sachiko
authors: S
authors: Sato
mesh_terms: D037483:Galectin 1 / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008954:Models, Biological; D011134:Polysaccharides / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D037483:Galectin 1; D015699:HIV Envelope Protein gp120; D011134:Polysaccharides; C514793:gp120 protein, Human immunodeficiency virus 1