Endothelial galectin-1 binds to specific glycans on nipah virus fusion protein and inhibits maturation, mobility, and function to block syncytia formation.
Nipah virus targets human endothelial cells via NiV-F and NiV-G envelope glycoproteins, resulting in endothelial syncytia formation and vascular compromise. Endothelial cells respond to viral infection by releasing innate immune effectors, including galectins, which are secreted proteins that bind to specific glycan ligands on cell surface glycoproteins. We demonstrate that galectin-1 reduces NiV-F mediated fusion of endothelial cells, and that endogenous galectin-1 in endothelial cells is sufficient to inhibit syncytia formation. Galectin-1 regulates NiV-F mediated cell fusion at three distinct points, including retarding maturation of nascent NiV-F, reducing NiV-F lateral mobility on the plasma membrane, and directly inhibiting the conformational change in NiV-F required for triggering fusion. Characterization of the NiV-F N-glycome showed that the critical site for galectin-1 inhibition is rich in glycan structures known to bind galectin-1. These studies identify a unique set of mechanisms for regulating pathophysiology of NiV infection at the level of the target cell.
Garner
Omai B
OB
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
Aguilar
Hector C
HC
Fulcher
Jennifer A
JA
Levroney
Ernest L
EL
Harrison
Rebecca
R
Wright
Lacey
L
Robinson
Lindsey R
LR
Aspericueta
Vanessa
V
Panico
Maria
M
Haslam
Stuart M
SM
Morris
Howard R
HR
Dell
Anne
A
Lee
Benhur
B
Baum
Linda G
LG
D002478:Cells, Cultured; D042783:Endothelial Cells / Q000821:virology; D037483:Galectin 1 / Q000378:metabolism* / Q000494:pharmacology*; D015726:Giant Cells / Q000187:drug effects*; D045464:Henipavirus Infections; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects; D045405:Nipah Virus / Q000737:chemistry*; D011134:Polysaccharides / Q000378:metabolism*; D011485:Protein Binding; D014760:Viral Fusion Proteins / Q000378:metabolism*; D018406:Virus Physiological Phenomena / Q000187:drug effects*
D037483:Galectin 1; D011134:Polysaccharides; D014760:Viral Fusion Proteins