title: CX3CR1 Is Expressed in Differentiated Human Ciliated Airway Cells and Co-Localizes with Respiratory Syncytial Virus on Cilia in a G Protein-Dependent Manner.
abstract: Respiratory syncytial virus (RSV) is the principal cause of bronchiolitis in infants and a significant healthcare problem. The RSV Glycoprotein (G) mediates attachment of the virus to the cell membrane, which facilitates interaction of the RSV Fusion (F) protein with nucleolin, thereby triggering fusion of the viral and cellular membranes. However, a host protein ligand for G has not yet been identified. Here we show that CX3CR1 is expressed in the motile cilia of differentiated human airway epithelial (HAE) cells, and that CX3CR1 co-localizes with RSV particles. Upon infection, the distribution of CX3CR1 in these cells is significantly altered. Complete or partial deletion of RSV G results in viruses binding at least 72-fold less efficiently to cells, and reduces virus replication. Moreover, an antibody targeting an epitope near the G protein's CX3CR1-binding motif significantly inhibits binding of the virus to airway cells. Given previously published evidence of the interaction of G with CX3CR1 in human lymphocytes, these findings suggest a role for G in the interaction of RSV with ciliated lung cells. This interpretation is consistent with past studies showing a protective benefit in immunizing against G in animal models of RSV infection, and would support targeting the CX3CR1-G protein interaction for prophylaxis or therapy. CX3CR1 expression in lung epithelial cells may also have implications for other respiratory diseases such as asthma.
authors.affiliation: Sanofi Pasteur, Research North America, 38 Sidney St., Cambridge, MA 02139, United States of America.
authors.forename: Kwang-Il
authors.initials: KI
authors.lastname: Jeong
authors.affiliation: Genzyme, Department of Pathology, 5 The Mountain Rd., Framingham, MA 01701, United States of America.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Piepenhagen
authors.affiliation: Sanofi Pasteur, Research North America, 38 Sidney St., Cambridge, MA 02139, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Kishko
authors.affiliation: Sanofi Pasteur, Research North America, 38 Sidney St., Cambridge, MA 02139, United States of America.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: DiNapoli
authors.affiliation: Sanofi Pasteur, Research North America, 38 Sidney St., Cambridge, MA 02139, United States of America.
authors.forename: Rachel P
authors.initials: RP
authors.lastname: Groppo
authors.affiliation: Sanofi Pasteur, Research North America, 38 Sidney St., Cambridge, MA 02139, United States of America.
authors.forename: Linong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Sanofi Pasteur, Research North America, 38 Sidney St., Cambridge, MA 02139, United States of America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Almond
authors.affiliation: Sanofi Pasteur, Research North America, 38 Sidney St., Cambridge, MA 02139, United States of America.
authors.forename: Harry
authors.initials: H
authors.lastname: Kleanthous
authors.affiliation: Sanofi Pasteur, Research North America, 38 Sidney St., Cambridge, MA 02139, United States of America.
authors.forename: Simon
authors.initials: S
authors.lastname: Delagrave
authors.affiliation: Sanofi Pasteur, Research North America, 38 Sidney St., Cambridge, MA 02139, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Parrington
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D000073883:CX3C Chemokine Receptor 1; D002454:Cell Differentiation; D002648:Child; D002923:Cilia / Q000378:metabolism / Q000473:pathology / Q000821:virology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D061251:Primary Cell Culture; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D000906:Antibodies; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D000939:Epitopes; D019707:Receptors, Chemokine; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; C116204:attachment protein G