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| Status |
Public on Sep 30, 2024 |
| Title |
Activation of STAT3-mediated ciliated cell survival protects against severe infection by respiratory syncytial virus |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia mostly in infants. To identify molecular targets of intervention during RSV infection in infants, we investigate how age regulates RSV interaction with the bronchial epithelium barrier. Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium. In contrast, adult bronchial epithelium showed insignificant barrier damage and limited RSV infection. Single nuclear RNA-sequencing revealed age-related insufficiency of an anti-apoptotic STAT3 activation response to RSV infection in infant ciliated cells, which was exploited to facilitate virus spread via the extruded apoptotic ciliated cells carrying RSV. Activation of STAT3 and blockade of apoptosis rendered protection against severe RSV infection in infant bronchial epithelium. Lastly, apoptotic inhibitor treatment of a neonatal mouse model of RSV infection ameliorated infection and inflammation in the lung. Taken together, our findings identify a STAT3-mediated anti-apoptosis pathway as a target to battle severe RSV disease in infants.
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| Overall design |
Single nuclei of neonatal and adult air-liquid-interface (ALI) cultures were dissociated and isolated at 1 day post RSV infection and analyzed using single-nuclei RNA sequencing
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| Contributor(s) |
Zhao C, Ai X |
| Citation missing |
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| Submission date |
Aug 09, 2024 |
| Last update date |
Oct 01, 2024 |
| Contact name |
Caiqi Zhao |
| E-mail(s) |
czhao12@mgh.harvard.edu
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| Organization name |
MGH
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| Street address |
55 Fruit St
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| City |
Boston |
| ZIP/Postal code |
02114 |
| Country |
USA |
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| Platforms (1) |
| GPL34281 |
Illumina NovaSeq X (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1146463 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE274466_RAW.tar |
1.4 Gb |
(http)(custom) |
TAR (of MTX, TSV) |
| GSE274466_features.tsv.gz |
287.7 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
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