title: CX3CR1 is an important surface molecule for respiratory syncytial virus infection in human airway epithelial cells.
abstract: Respiratory syncytial virus (RSV) is a major cause of severe pneumonia and bronchiolitis in infants and young children, and causes disease throughout life. Understanding the biology of infection, including virus binding to the cell surface, should help develop antiviral drugs or vaccines. The RSV F and G glycoproteins bind cell surface heparin sulfate proteoglycans (HSPGs) through heparin-binding domains. The G protein also has a CX3C chemokine motif which binds to the fractalkine receptor CX3CR1. G protein binding to CX3CR1 is not important for infection of immortalized cell lines, but reportedly is so for primary human airway epithelial cells (HAECs), the primary site for human infection. We studied the role of CX3CR1 in RSV infection with CX3CR1-transfected cell lines and HAECs with variable percentages of CX3CR1-expressing cells, and the effect of anti-CX3CR1 antibodies or a mutation in the RSV CX3C motif. Immortalized cells lacking HSPGs had low RSV binding and infection, which was increased markedly by CX3CR1 transfection. CX3CR1 was expressed primarily on ciliated cells, and ∼50 % of RSV-infected cells in HAECs were CX3CR1+. HAECs with more CX3CR1-expressing cells had a proportional increase in RSV infection. Blocking G binding to CX3CR1 with anti-CX3CR1 antibody or a mutation in the CX3C motif significantly decreased RSV infection in HAECs. The kinetics of cytokine production suggested that the RSV/CX3CR1 interaction induced RANTES (regulated on activation normal T-cell expressed and secreted protein), IL-8 and fractalkine production, whilst it downregulated IL-15, IL1-RA and monocyte chemotactic protein-1. Thus, the RSV G protein/CX3CR1 interaction is likely important in infection and infection-induced responses of the airway epithelium, the primary site of human infection.
authors: Department of Pediatrics and Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia, USA.
authors: Tatiana
authors: T
authors: Chirkova
authors: Department of Pediatrics and Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia, USA.
authors: Songbai
authors: S
authors: Lin
authors: Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, USA.
authors: Antonius G P
authors: AGP
authors: Oomens
authors: Department of Pediatrics and Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia, USA.
authors: Kelsey A
authors: KA
authors: Gaston
authors: Department of Pediatrics and Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia, USA.
authors: Seyhan
authors: S
authors: Boyoglu-Barnum
authors: Department of Pediatrics and Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia, USA.
authors: Jia
authors: J
authors: Meng
authors: Department of Pediatrics and Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia, USA.
authors: Christopher C
authors: CC
authors: Stobart
authors: Division of Pediatric Pulmonology, Case Western University, Cleveland, Ohio, USA.
authors: Calvin U
authors: CU
authors: Cotton
authors: Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine and Vanderbilt Center for Asthma and Environmental Health Sciences Research, Vanderbilt University, Nashville, Tennessee, USA.
authors: Tina V
authors: TV
authors: Hartert
authors: Department of Pediatrics and Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia, USA.
authors: Martin L
authors: ML
authors: Moore
authors: Department of Pediatrics and Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia, USA.
authors: Assem G
authors: AG
authors: Ziady
authors: Department of Pediatrics and Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia, USA.
authors: Larry J
authors: LJ
authors: Anderson
mesh_terms: D020816:Amino Acid Motifs; D000073883:CX3C Chemokine Receptor 1; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology; D006801:Humans; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000502:physiology*; D012137:Respiratory System / Q000166:cytology / Q000378:metabolism / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D019707:Receptors, Chemokine; D014759:Viral Envelope Proteins