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

• Published in: The Journal of Infectious Diseases 2017-11, Vol.216 (8), p.1027-1037
• Main Authors: Mariani, Thomas J., Qiu, Xing, Chu, ChinYi, Wang, Lu, Thakar, Juilee, Holden-Wiltse, Jeanne, Corbett, Anthony, Topham, David J., Falsey, Ann R., Caserta, Mary T., Walsh, Edward E.
• Format: Article
• Language: English
• Subjects: CD4-Positive T-Lymphocytes - immunology; Cohort Studies; Female; Humans; Infant; Infant, Newborn; Major and Brief Reports; Male; PATHOGENESIS AND HOST RESPONSE; Respiratory Syncytial Virus Infections - genetics; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Virus, Human - immunology; Severity of Illness Index; Tobacco Smoke Pollution; Transcriptome
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jix400

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