title: Timing of galectin-1 exposure differentially modulates Nipah virus entry and syncytium formation in endothelial cells.
abstract: Nipah virus (NiV) is a deadly emerging enveloped paramyxovirus that primarily targets human endothelial cells. Endothelial cells express the innate immune effector galectin-1 that we have previously shown can bind to specific N-glycans on the NiV envelope fusion glycoprotein (F). NiV-F mediates fusion of infected endothelial cells into syncytia, resulting in endothelial disruption and hemorrhage. Galectin-1 is an endogenous carbohydrate-binding protein that binds to specific glycans on NiV-F to reduce endothelial cell fusion, an effect that may reduce pathophysiologic sequelae of NiV infection. However, galectins play multiple roles in regulating host-pathogen interactions; for example, galectins can promote attachment of HIV to T cells and macrophages and attachment of HSV-1 to keratinocytes but can also inhibit influenza entry into airway epithelial cells. Using live Nipah virus, in the present study, we demonstrate that galectin-1 can enhance NiV attachment to and infection of primary human endothelial cells by bridging glycans on the viral envelope to host cell glycoproteins. In order to exhibit an enhancing effect, galectin-1 must be present during the initial phase of virus attachment; in contrast, addition of galectin-1 postinfection results in reduced production of progeny virus and syncytium formation. Thus, galectin-1 can have dual and opposing effects on NiV infection of human endothelial cells. While various roles for galectin family members in microbial-host interactions have been described, we report opposing effects of the same galectin family member on a specific virus, with the timing of exposure during the viral life cycle determining the outcome.
  
  
  OBJECTIVE
  Nipah virus is an emerging pathogen that targets endothelial cells lining blood vessels; the high mortality rate (up to 70%) in Nipah virus infections results from destruction of these cells and resulting catastrophic hemorrhage. Host factors that promote or prevent Nipah virus infection are not well understood. Endogenous human lectins, such as galectin-1, can function as pattern recognition receptors to reduce infection and initiate immune responses; however, lectins can also be exploited by microbes to enhance infection of host cells. We found that galectin-1, which is made by inflamed endothelial cells, can both promote Nipah virus infection of endothelial cells by "bridging" the virus to the cell, as well as reduce production of progeny virus and reduce endothelial cell fusion and damage, depending on timing of galectin-1 exposure. This is the first report of spatiotemporal opposing effects of a host lectin for a virus in one type of host cell.
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Omai B
authors.initials: OB
authors.lastname: Garner
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Yun
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Pernet
authors.affiliation: Paul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
authors.forename: Hector C
authors.initials: HC
authors.lastname: Aguilar
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Arnold
authors.initials: A
authors.lastname: Park
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bowden
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Freiberg
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA benhur.lee@mssm.ed lbaum@mednet.ucla.edu.
authors.forename: Benhur
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA benhur.lee@mssm.ed lbaum@mednet.ucla.edu.
authors.forename: Linda G
authors.initials: LG
authors.lastname: Baum
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology / Q000502:physiology* / Q000821:virology*; D037483:Galectin 1 / Q000276:immunology / Q000378:metabolism*; D015726:Giant Cells / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D045405:Nipah Virus / Q000276:immunology / Q000502:physiology*; D053586:Virus Internalization
chemical_list: D037483:Galectin 1; C445499:LGALS1 protein, human