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. 2024 Nov 1;134(21):e185689.
doi: 10.1172/JCI185689.

Enhanced susceptibility of pediatric airway epithelium to respiratory syncytial virus infection

Raymond J Pickles  1   2 , Gang Chen  1   3 , Scott H Randell  1   4
Affiliations

Enhanced susceptibility of pediatric airway epithelium to respiratory syncytial virus infection

Raymond J Pickles et al. J Clin Invest. .

Abstract

Immature innate and adaptive immunity and vulnerability of narrower airways to obstruction increase the susceptibility of infants to severe respiratory syncytial virus (RSV) disease. In this issue of the JCI, Zhao et al. illustrated greater intrinsic susceptibility of pediatric versus adult airway epithelial cells to RSV-induced cytopathology. Using precision cut lung slices (PCLS) and air-liquid interface (ALI) airway epithelial cell cultures, the authors showed that impaired STAT3 activation in RSV-infected pediatric multiciliated cells increased cell apoptosis and viral shedding, which enhanced the spread of infection. Bolstering STAT3 activation and treatment of neonatal mice with apoptosis inhibitors suppressed virus spread, suggesting that enhancing STAT3 activation may provide therapeutic benefit.

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Conflict of interest statement

Conflict of interest: SHR has patents, including “Light-triggered wound mimicking system”, U.S. Provisional Application No. 63/595,790; “Inhibition of the Epithelial Sodium Channel by the Cereblon E3 Ubiquitin Ligase Modulator, CC-90009”, U.S. Provisional Application No. 63/248,765; “Respiratory Delivery of Therapeutic Agents”, U.S. Provisional Application No. 63/256,416; “Epithelial Cell Spheroids and Methods of Making and Using the Same”, Patent No. US11357758B2; “Human Conducting Airway Model Comprising Multiple Fluidic Pathways”, Patent No. US2014335496A1. RJP has a patent titled “Targeted gene transfer using G protein coupled receptors”, United States Patent Application Publication 20030004123.

Figures

Figure 1
Figure 1. STAT3 hypoactivation in neonatal/pediatric airway epithelial cells increases spread of RSV infection.
RSV infection of airway epithelial cells from infant and adult lung tissue triggers STAT3 phosphorylation, causing STAT3 activation and nuclear translocation, particularly in multiciliated and basal cells. This process can be mediated by Janus kinase (JAK) following the binding of various ligands and agonists to their respective receptor complexes following infection. In pediatric airway epithelial cells, reduced STAT3 activation in response to RSV results in increased apoptosis, cell shedding, and mucin production compared with adult airway cells. Safely managing epithelial STAT3 activation may be a viable therapeutic strategy to control RSV infection in neonates.
See this image and copyright information in PMC

Comment on

  • Activation of STAT3-mediated ciliated cell survival protects against severe infection by respiratory syncytial virus

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