Association of Dynamic Changes in the CD4 T-Cell Transcriptome With Disease Severity During Primary Respiratory Syncytial Virus Infection in Young Infants

J Infect Dis. 2017 Nov 15;216(8):1027-1037. doi: 10.1093/infdis/jix400.

Abstract

Background: Nearly all children are infected with respiratory syncytial virus (RSV) within the first 2 years of life, with a minority developing severe disease (1%-3% hospitalized). We hypothesized that an assessment of the adaptive immune system, using CD4+ T-lymphocyte transcriptomics, would identify gene expression correlates of disease severity.

Methods: Infants infected with RSV representing extremes of clinical severity were studied. Mild illness (n = 23) was defined as a respiratory rate (RR) < 55 and room air oxygen saturation (SaO2) ≥ 97%, and severe illness (n = 23) was defined as RR ≥ 65 and SaO2 ≤ 92%. RNA from fresh, sort-purified CD4+ T cells was assessed by RNA sequencing.

Results: Gestational age, age at illness onset, exposure to environmental tobacco smoke, bacterial colonization, and breastfeeding were associated (adjusted P < .05) with disease severity. RNA sequencing analysis reliably measured approximately 60% of the genome. Severity of RSV illness had the greatest effect size upon CD4 T-cell gene expression. Pathway analysis identified correlates of severity, including JAK/STAT, prolactin, and interleukin 9 signaling. We also identified genes and pathways associated with timing of symptoms and RSV group (A/B).

Conclusions: These data suggest fundamental changes in adaptive immune cell phenotypes may be associated with RSV clinical severity.

Keywords: RNA sequencing; T cell; disease severity; gene espression; respiratory syncytial virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • Cohort Studies
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Respiratory Syncytial Virus Infections / genetics*
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Virus, Human / immunology*
  • Severity of Illness Index
  • Tobacco Smoke Pollution
  • Transcriptome*

Substances

  • Tobacco Smoke Pollution