title: Gene expression profiles during in vivo human rhinovirus infection: insights into the host response.
abstract: BACKGROUND
  Human rhinovirus infections cause colds and trigger exacerbations of lower airway diseases.
  
  
  OBJECTIVE
  To define changes in gene expression profiles during in vivo rhinovirus infections.
  
  
  METHODS
  Nasal epithelial scrapings were obtained before and during experimental rhinovirus infection, and gene expression was evaluated by microarray. Naturally acquired rhinovirus infections, cultured human epithelial cells, and short interfering RNA knockdown were used to further evaluate the role of viperin in rhinovirus infections.
  
  
  RESULTS
  Symptom scores and viral titers were measured in subjects inoculated with rhinovirus or sham control, and changes in gene expression were assessed 8 and 48 hours after inoculation. Real-time reverse transcription-polymerase chain reaction for viperin and rhinoviruses was used in naturally acquired infections, and viperin mRNA levels and viral titers were measured in cultured cells. Rhinovirus-induced changes in gene expression were not observed 8 hours after viral infection, but 11,887 gene transcripts were significantly altered in scrapings obtained 2 days postinoculation. Major groups of up-regulated genes included chemokines, signaling molecules, interferon-responsive genes, and antivirals. Viperin expression was further examined and also was increased in naturally acquired rhinovirus infections, as well as in cultured human epithelial cells infected with intact, but not replication-deficient, rhinovirus. Knockdown of viperin with short interfering RNA increased rhinovirus replication in infected epithelial cells.
  
  
  CONCLUSIONS
  Rhinovirus infection significantly alters the expression of many genes associated with the immune response, including chemokines and antivirals. The data obtained provide insights into the host response to rhinovirus infection and identify potential novel targets for further evaluation.
authors.affiliation: Department of Physiology and Biophysics, Health Sciences 1626, University of Calgary Faculty of Medicine, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1 Canada. dproud@ucalgary.ca
authors.forename: David
authors.initials: D
authors.lastname: Proud
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Turner
authors.forename: Birgit
authors.initials: B
authors.lastname: Winther
authors.forename: Shahina
authors.initials: S
authors.lastname: Wiehler
authors.forename: Jay P
authors.initials: JP
authors.lastname: Tiesman
authors.forename: Tim D
authors.initials: TD
authors.lastname: Reichling
authors.forename: Kenton D
authors.initials: KD
authors.lastname: Juhlin
authors.forename: Andy W
authors.initials: AW
authors.lastname: Fulmer
authors.forename: Begonia Y
authors.initials: BY
authors.lastname: Ho
authors.forename: Amy A
authors.initials: AA
authors.lastname: Walanski
authors.forename: Cathy L
authors.initials: CL
authors.lastname: Poore
authors.forename: Haruko
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Lynn
authors.initials: L
authors.lastname: Jump
authors.forename: Marsha L
authors.initials: ML
authors.lastname: Moore
authors.forename: Claudine K
authors.initials: CK
authors.lastname: Zukowski
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Clymer
mesh_terms: D000293:Adolescent; D018929:Cell Culture Techniques; D018925:Chemokines / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010850:Picornaviridae Infections / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012229:Rhinovirus / Q000235:genetics*; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult; D000090123:Viperin Protein
chemical_list: D018925:Chemokines; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins; C444427:RSAD2 protein, human; D000090123:Viperin Protein