title: Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus.
abstract: OBJECTIVE
  Human airway epithelial cells are the principal target of human rhinovirus (HRV), a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1) to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2) to identify gene expression patterns associated with asthma intrinsically and/or after HRV infection using this model.
  
  
  METHODS
  Air-liquid interface (ALI) human airway epithelial cell cultures were prepared from 6 asthmatic and 6 non-asthmatic donors. The effects of rhinovirus RV-A16 on ALI cultures were compared. Genome-wide gene expression changes in ALI cultures following HRV infection at 24 hours post exposure were further analyzed using RNA-seq technology. Cellular gene expression and cytokine/chemokine secretion were further evaluated by qPCR and a Luminex-based protein assay, respectively.
  
  
  RESULTS
  ALI cultures were readily infected by HRV. RNA-seq analysis of HRV infected ALI cultures identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial structure and remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1, MUC5AC, CDHR3), and novel ones that were identified for the first time in this study (e.g. CCRL1).
  
  
  CONCLUSIONS
  ALI-cultured human airway epithelial cells challenged with HRV are a useful translational model for the study of HRV-induced responses in airway epithelial cells, given that gene expression profile using this model largely recapitulates some important patterns of gene responses in patients during clinical HRV infection. Furthermore, our data emphasize that both abnormal airway epithelial structure and inflammatory signaling are two important asthma signatures, which can be further exacerbated by HRV infection.
authors.affiliation: Merck Research Laboratories, Boston, Massachusetts, United States of America.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Bai
authors.affiliation: Merck Research Laboratories, Boston, Massachusetts, United States of America.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Smock
authors.affiliation: MatTek Corporation, Ashland, Massachusetts, United States of America.
authors.forename: George R
authors.initials: GR
authors.lastname: Jackson
authors.affiliation: Merck Research Laboratories, Boston, Massachusetts, United States of America.
authors.forename: Kenzie D
authors.initials: KD
authors.lastname: MacIsaac
authors.affiliation: Merck Research Laboratories, Boston, Massachusetts, United States of America.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Huang
authors.affiliation: MatTek Corporation, Ashland, Massachusetts, United States of America.
authors.forename: Courtney
authors.initials: C
authors.lastname: Mankus
authors.affiliation: MatTek Corporation, Ashland, Massachusetts, United States of America.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Oldach
authors.affiliation: Merck Research Laboratories, Boston, Massachusetts, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Roberts
authors.affiliation: Merck Research Laboratories, Boston, Massachusetts, United States of America.
authors.forename: Yu-Lu
authors.initials: YL
authors.lastname: Ma
authors.affiliation: Merck Research Laboratories, Boston, Massachusetts, United States of America.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Klappenbach
authors.affiliation: Merck Research Laboratories, Boston, Massachusetts, United States of America.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Crackower
authors.affiliation: Merck Research Laboratories, Boston, Massachusetts, United States of America.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Alves
authors.affiliation: MatTek Corporation, Ashland, Massachusetts, United States of America.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hayden
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics* / Q000821:virology*; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics; D002648:Child; D004847:Epithelial Cells / Q000821:virology*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D010850:Picornaviridae Infections / Q000235:genetics* / Q000821:virology; D012137:Respiratory System / Q000821:virology*; D012229:Rhinovirus; D015398:Signal Transduction / Q000235:genetics
chemical_list: D018925:Chemokines