Endothelial galectin-1 binds to specific glycans on nipah virus fusion protein and inhibits maturation, mobility, and function to block syncytia formation

Omai B Garner; Hector C Aguilar; Jennifer A Fulcher; Ernest L Levroney; Rebecca Harrison; Lacey Wright; Lindsey R Robinson; Vanessa Aspericueta; Maria Panico; Stuart M Haslam; Howard R Morris; Anne Dell; Benhur Lee; Linda G Baum

doi:10.1371/journal.ppat.1000993

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Endothelial galectin-1 binds to specific glycans on nipah virus fusion protein and inhibits maturation, mobility, and function to block syncytia formation

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Endothelial galectin-1 binds to specific glycans on nipah virus fusion protein and inhibits maturation, mobility, and function to block syncytia formation

Omai B Garner, Hector C Aguilar, Jennifer A Fulcher, Ernest L Levroney, Rebecca Harrison, Lacey Wright, Lindsey R Robinson, Vanessa Aspericueta, Maria Panico, Stuart M Haslam, …

PLoS pathogens, Vol.6(7), pp.e1000993-14

07/15/2010

DOI: https://doi.org/10.1371/journal.ppat.1000993

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https://hdl.handle.net/2376/109652

PMCID: PMC2904771

PMID: 20657665

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https://doi.org/10.1371/journal.ppat.1000993View

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Abstract

Galectin 1 - pharmacology

Viral Fusion Proteins - metabolism

Giant Cells - drug effects

Humans

Cells, Cultured

Galectin 1 - metabolism

Polysaccharides - metabolism

Henipavirus Infections

Protein Binding

Virus Physiological Phenomena - drug effects

Endothelial Cells - virology

Membrane Fusion - drug effects

Nipah Virus - chemistry

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.

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Title: Endothelial galectin-1 binds to specific glycans on nipah virus fusion protein and inhibits maturation, mobility, and function to block syncytia formation
Creators: Omai B Garner - Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
Hector C Aguilar
Jennifer A Fulcher
Ernest L Levroney
Rebecca Harrison
Lacey Wright
Lindsey R Robinson
Vanessa Aspericueta
Maria Panico
Stuart M Haslam
Howard R Morris
Anne Dell
Benhur Lee
Linda G Baum
Publication Details: PLoS pathogens, Vol.6(7), pp.e1000993-14
Academic Unit: Paul G. Allen School for Global Animal Health
Publisher: United States
Grant note: AI065359 / NIAID NIH HHS BBF0083091 / Biotechnology and Biological Sciences Research Council R01AI070495 / NIAID NIH HHS R01AI069317 / NIAID NIH HHS SF19107 / Biotechnology and Biological Sciences Research Council T32 HL069766 / NHLBI NIH HHS B19088 / Biotechnology and Biological Sciences Research Council U01 AI070495 / NIAID NIH HHS R01 AI060694 / NIAID NIH HHS R01 AI069317 / NIAID NIH HHS U54 AI065359 / NIAID NIH HHS R01AI060694 / NIAID NIH HHS T32HL69766 / NHLBI NIH HHS
Identifiers: 99900547223701842
Language: English
Resource Type: Journal article