title: Viral Specific Factors Contribute to Clinical Respiratory Syncytial Virus Disease Severity Differences in Infants.
abstract: BACKGROUND
  There is a wide range of severity of respiratory syncytial viral (RSV) disease in previously healthy infants. Host factors have been well demonstrated to contribute to disease severity differences. However the possibility of disease severity differences being produced by factors intrinsic to the virus itself has rarely been studied.
  
  
  METHODS
  Low-passage isolates of RSV collected prospectively from infants with different degrees of RSV disease severity were evaluatedin vitro, holding host factors constant, so as to assess whether isolates induced phenotypically different cytokine/chemokine concentrations in a human lung epithelial cell line. Sixty-seven RSV isolates from previously healthy infants (38 hospitalized for acute RSV infection (severe disease) and 29 never requiring hospitalization (mild disease)) were inoculated into A549, lung epithelial cells at precisely controlled, low multiplicity of infection to mimic natural infection. Cultures were evaluated at 48 hours, 60 hours, and 72 hours to evaluate area under the curve (AUC) cytokine/chemokine induction.
  
  
  RESULTS
  Cells infected with isolates from severely ill infants produced higher mean concentrations of all cytokine/chemokines tested (IL-1α, IL-6, IL-8 and RANTES) at all-time points tested. RSV isolates collected from infants with severe disease induced significantly higher AUCIL-8 and AUCRANTES secretion in infected cultures than mild disease isolates (p=0.028 and p=0.019 respectively). IL-8 and RANTES concentrations were 4 times higher at 48 hours for these severely ill infant isolates. Additionally, 38 isolates were evaluated at all-time points for quantity of virus. RSV concentration significantly correlated with both IL-8 and RANTES at all-time points. Neither cytokine/chemokine concentrations nor RSV concentrations were associated with RSV subgroup.
  
  
  CONCLUSIONS
  Infants' RSV disease severity differences may be due in part to intrinsic viral strain-specific characteristics.
authors.affiliation: University of Tennessee School of Medicine, Department of Pediatrics ; University of Arkansas for Medical Sciences, Department of Pediatric Emergency Medicine, Little Rock, AR 72202.
authors.forename: Tonya M
authors.initials: TM
authors.lastname: Thompson
authors.affiliation: University of Tennessee School of Medicine, Department of Pediatrics ; Le Bonheur Children's Hospital ; The Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, TN 38103.
authors.forename: Philippa L
authors.initials: PL
authors.lastname: Roddam
authors.affiliation: University of Tennessee School of Medicine, Department of Pediatrics ; Le Bonheur Children's Hospital ; The Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, TN 38103.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Harrison
authors.affiliation: University of Tennessee School of Medicine, Department of Pediatrics ; Le Bonheur Children's Hospital ; The Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, TN 38103.
authors.forename: Jody A
authors.initials: JA
authors.lastname: Aitken
authors.affiliation: University of Tennessee School of Medicine, Department of Pediatrics ; University of Tennessee Graduate School of Health Sciences, Department of Molecular Sciences ; Le Bonheur Children's Hospital ; The Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, TN 38103.
authors.forename: John P
authors.initials: JP
authors.lastname: DeVincenzo
keywords: Chemokines; Clinical isolates; Cytokines; Disease severity; Respiratory syncytial virus (RSV)