Endothelial Galectin-1 Binds to Specific Glycans on Nipah Virus Fusion Protein and Inhibits Maturation, Mobility, and Function to Block Syncytia Formation

PLoS Pathogens

Lindsey R. Robinson¹  Vanessa Aspericueta¹  Hector C. Aguilar¹  Ernest L. Levroney¹  Omai B. Garner²  Lacey Wright²  Linda G. Baum²  Jennifer A. Fulcher²  Maria Panico³  Rebecca Harrison³  Stuart M. Haslam³  Benhur Lee³  Howard R. Morris³  Anne Dell⁴ 

[1] Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America;Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America;Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College, London, United Kingdom;MSCAN Ltd., Millars Business Centre, Wokingham, Berks, United Kingdom

关键词: Cell fusion;    Endothelial cells;    Endocytosis;    Membrane fusion;    Glycoproteins;    Virus glycoproteins;    Cell binding;    Small interfering RNAs;   

DOI  :  10.1371/journal.ppat.1000993

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY