title: Rhinovirus Detection in Symptomatic and Asymptomatic Children: Value of Host Transcriptome Analysis.
abstract: BACKGROUND
  Rhinoviruses (RVs) are a major cause of symptomatic respiratory tract infection in all age groups. However, RVs can frequently be detected in asymptomatic individuals.
  
  
  OBJECTIVE
  To evaluate the ability of host transcriptional profiling to differentiate between symptomatic RV infection and incidental detection in children.
  
  
  METHODS
  Previously healthy children younger than 2 years old (n = 151) were enrolled at four study sites and classified into four clinical groups: RV- healthy control subjects (n = 37), RV+ asymptomatic subjects (n = 14), RV+ outpatients (n = 30), and RV+ inpatients (n = 70). Host responses were analyzed using whole-blood RNA transcriptional profiles.
  
  
  RESULTS
  RV infection induced a robust transcriptional signature, which was validated in three independent cohorts and by quantitative real-time polymerase chain reaction with high prediction accuracy. The immune profile of symptomatic RV infection was characterized by overexpression of innate immunity and underexpression of adaptive immunity genes, whereas negligible changes were observed in asymptomatic RV+ subjects. Unsupervised hierarchical clustering identified two main clusters of subjects. The first included 93% of healthy control subjects and 100% of asymptomatic RV+ subjects, and the second comprised 98% of RV+ inpatients and 88% of RV+ outpatients. Genomic scores of healthy control subjects and asymptomatic RV+ children were similar and significantly lower than those of RV+ inpatients and outpatients (P < 0.0001).
  
  
  CONCLUSIONS
  Symptomatic RV infection induced a robust and reproducible transcriptional signature, whereas identification of RV in asymptomatic children was not associated with significant systemic transcriptional immune responses. Transcriptional profiling represents a useful tool to discriminate between active infection and incidental virus detection.
authors.affiliation: 1 Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, and.
authors.forename: Santtu
authors.initials: S
authors.lastname: Heinonen
authors.affiliation: 2 Department of Pediatrics and.
authors.forename: Tuomas
authors.initials: T
authors.lastname: Jartti
authors.affiliation: 3 Division of Pediatric Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Carla
authors.initials: C
authors.lastname: Garcia
authors.affiliation: 4 Division of Pediatric Emergency Medicine and Critical Care, Regional University Hospital of Malaga, Malaga, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Oliva
authors.affiliation: 5 Baylor Institute for Immunology Research, Dallas, Texas.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Smitherman
authors.affiliation: 5 Baylor Institute for Immunology Research, Dallas, Texas.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Anguiano
authors.affiliation: 6 Department of Pediatric Immunology and Infectious Diseases, The Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, the Netherlands; and.
authors.forename: Wouter A A
authors.initials: WA
authors.lastname: de Steenhuijsen Piters
authors.affiliation: 7 Department of Clinical Virology, Turku University Hospital, Turku, Finland.
authors.forename: Tytti
authors.initials: T
authors.lastname: Vuorinen
authors.affiliation: 2 Department of Pediatrics and.
authors.forename: Olli
authors.initials: O
authors.lastname: Ruuskanen
authors.affiliation: 1 Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, and.
authors.forename: Blerta
authors.initials: B
authors.lastname: Dimo
authors.affiliation: 1 Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, and.
authors.forename: Nicolas M
authors.initials: NM
authors.lastname: Suarez
authors.affiliation: 5 Baylor Institute for Immunology Research, Dallas, Texas.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual
authors.affiliation: 1 Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, and.|8 Division of Pediatric Infectious Diseases, Nationwide Children's Hospital, Columbus, Ohio.|9 The Ohio State University College of Medicine, Columbus, Ohio.
authors.forename: Octavio
authors.initials: O
authors.lastname: Ramilo
authors.affiliation: 1 Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, and.|8 Division of Pediatric Infectious Diseases, Nationwide Children's Hospital, Columbus, Ohio.|9 The Ohio State University College of Medicine, Columbus, Ohio.
authors.forename: Asuncion
authors.initials: A
authors.lastname: Mejias
mesh_terms: D058345:Asymptomatic Infections; D015415:Biomarkers / Q000097:blood; D001772:Blood Cell Count; D005260:Female; D005387:Finland; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007223:Infant; D008297:Male; D009820:Ohio; D010850:Picornaviridae Infections / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000821:virology*; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012141:Respiratory Tract Infections / Q000097:blood / Q000235:genetics / Q000821:virology*; D012229:Rhinovirus / Q000235:genetics / Q000302:isolation & purification*; D013030:Spain; D013781:Texas
chemical_list: D015415:Biomarkers
keywords: asymptomatic; children; rhinovirus; transcriptional profiling; viral detection