title: Chemokine-receptor upregulation and disease severity in respiratory syncytial virus infection.
abstract: Respiratory Syncytial Virus (RSV) infection is an important cause of severe infant bronchiolitis, partly due to lower airway inflammation orchestrated by virus-induced chemokine secretion. Chemokine receptors may therefore be therapeutic targets. We investigated RSV-induced chemokine receptor (CCR) 1, 2 and 5 surface expressions in a cellular model and in infants. RSV infection increased human monocytic CCR1, 2 and 5 expression, as assessed by FACS, via replication-dependent mechanisms. CCR1 and CCR5 levels peaked at 36 h and CCR2 levels at 48 h. Monocytes from infants with RSV-bronchiolitis significantly increased CCR1 expression after ex vivo RSV infection compared to controls. Expression of CCR5 also increased, and correlated with CCR1 expression (r=0.78, p<0.0001). CCR1 upregulation correlated with disease severity markers. Monocyte CCR1 receptors were functionally active as stimulation resulted in calcium influx. CCR1/5 blocking strategies may be useful in decreasing cellular inflammation in RSV infection.
authors.affiliation: Department of Infectious Diseases and Immunity, Hammersmith Campus, Imperial College London, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Morrison
authors.forename: Mike
authors.initials: M
authors.lastname: Sharland
authors.forename: Lynette H
authors.initials: LH
authors.lastname: Thomas
authors.forename: Soumendu
authors.initials: S
authors.lastname: Manna
authors.forename: Jenny
authors.initials: J
authors.lastname: Handforth
authors.forename: Shane
authors.initials: S
authors.lastname: Tibby
authors.forename: Jon S
authors.initials: JS
authors.lastname: Friedland
mesh_terms: D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007223:Infant; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D054389:Receptors, CCR1 / Q000096:biosynthesis*; D054390:Receptors, CCR2 / Q000096:biosynthesis*; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism* / Q000503:physiopathology*; D015854:Up-Regulation
chemical_list: C515300:CCR1 protein, human; C515334:CCR2 protein, human; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019713:Receptors, CCR5