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

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

Author information

1
Division of Neonatology and Pediatric Molecular and Personalized Medicine Program.
2
Department of Medicine, University of Rochester Medical Center.
3
Department of Biostatistics and Computational Biology.
4
Department of Microbiology and Immunology.
5
Department of Medicine, Rochester General Hospital, Rochester, New York.
6
Division of Pediatric Infectious Diseases.

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

PMID:
28962005
PMCID:
PMC5853440
DOI:
10.1093/infdis/jix400
[Indexed for MEDLINE]
Free PMC Article

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