The interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis

PLoS One. 2017 Mar 7;12(3):e0172953. doi: 10.1371/journal.pone.0172953. eCollection 2017.

Abstract

Respiratory syncytial virus (RSV) causes significant infant morbidity and mortality. For decades severe RSV-induced disease was thought to result from an uncontrolled host response to viral replication, but recent work suggests that a strong innate immune response early in infection is protective. To shed light on host-virus interactions and the viral determinants of disease, copy numbers of five RSV genes (NS1, NS2, N, G, F) were measured by quantitative real-time polymerase chain reaction (qPCR) in nasal wash samples from children with RSV-associated bronchiolitis. Correlations were sought with host cytokines/chemokines and biomarkers. Associations with disposition from the emergency department (hospitalized or sent home) and pulse oximetry O2 saturation levels were also sought. Additionally, RNase P copy number was measured and used to normalize nasal wash data. RSV gene copy numbers were found to significantly correlate with both cytokine/chemokine and biomarker levels; and RNase P-normalized viral gene copy numbers (NS1, NS2, N and G) were significantly higher in infants with less severe disease. Moreover, three of the normalized viral gene copy numbers (NS1, NS2, and N) correlated significantly with arterial O2 saturation levels. The data support a model where a higher viral load early in infection can promote a robust innate immune response that protects against progression into hypoxic RSV-induced lower respiratory tract illness.

MeSH terms

  • Bronchiolitis / diagnosis
  • Bronchiolitis / immunology*
  • Bronchiolitis / virology*
  • Child, Preschool
  • Cytokines / metabolism
  • Emergency Service, Hospital
  • Female
  • Hospitalization
  • Humans
  • Immunity, Innate*
  • Infant
  • Infant, Newborn
  • Inflammation Mediators / metabolism
  • Male
  • Patient Outcome Assessment
  • Respiratory Syncytial Virus Infections / diagnosis
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / virology*
  • Respiratory Syncytial Virus, Human / immunology*
  • Risk Factors
  • Viral Load*

Substances

  • Cytokines
  • Inflammation Mediators

Grants and funding

This work was supported by the Department of Defense (https://urldefense.proofpoint.com/v2/url?u=http-3A__www.defense.gov_&d=DwIGaQ&c=ZQs-KZ8oxEw0p81sqgiaRA&r=8HfluFGqdfRYRuWe3HyiMA&m=PYV_85UrZLaXMsZpeX6cRhl19l8q2G5RutrxhnOWcMk&s=W5VY_4LzMqd1U6ND2m5hHnonN4l5-HBG7ygLctfsPEQ&e=) [W81XWH1010146 to RPG] and a Postdoctoral Fellowship from the National Institute of Environmental Health Sciences (https://urldefense.proofpoint.com/v2/url?u=http-3A__www.niehs.nih.gov_&d=DwIGaQ&c=ZQs-KZ8oxEw0p81sqgiaRA&r=8HfluFGqdfRYRuWe3HyiMA&m=PYV_85UrZLaXMsZpeX6cRhl19l8q2G5RutrxhnOWcMk&s=egZ4Nl6jAxKtJFK-tBHFo3Gy0OMiA1Q5EeZ72qgW7SM&e=) [T32-07254 to RM]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.