title: RAGE inhibits human respiratory syncytial virus syncytium formation by interfering with F-protein function.
abstract: Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection. Infection is critically dependent on the RSV fusion (F) protein, which mediates fusion between the viral envelope and airway epithelial cells. The F protein is also expressed on infected cells and is responsible for fusion of infected cells with adjacent cells, resulting in the formation of multinucleate syncytia. The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor that is constitutively highly expressed by type I alveolar epithelial cells. Here, we report that RAGE protected HEK cells from RSV-induced cell death and reduced viral titres in vitro. RAGE appeared to interact directly with the F protein, but, rather than inhibiting RSV entry into host cells, virus replication and budding, membrane-expressed RAGE or soluble RAGE blocked F-protein-mediated syncytium formation and sloughing. These data indicate that RAGE may contribute to protecting the lower airways from RSV by inhibiting the formation of syncytia, viral spread, epithelial damage and airway obstruction.
authors.affiliation: Research Department, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Tian
authors.affiliation: Research Department, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Huang
authors.affiliation: Research Department, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Research Department, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Svabek
authors.affiliation: Research Department, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Rowe
authors.affiliation: Research Department, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Yambasu
authors.initials: Y
authors.lastname: Brewah
authors.affiliation: Research Department, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Sanjuan
authors.affiliation: Research Department, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Andriani C
authors.initials: AC
authors.lastname: Patera
authors.affiliation: Research Department, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Roland
authors.initials: R
authors.lastname: Kolbeck
authors.affiliation: Research Department, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Herbst
authors.affiliation: Research Department, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Sims
mesh_terms: D002478:Cells, Cultured; D004847:Epithelial Cells / Q000821:virology*; D015726:Giant Cells / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D018113:Respiratory Syncytial Virus, Human / Q000472:pathogenicity*; D014760:Viral Fusion Proteins / Q000378:metabolism*
chemical_list: C526850:F protein, human respiratory syncytial virus; D000067759:Receptor for Advanced Glycation End Products; D014760:Viral Fusion Proteins
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