About: Insufficiency in airway interferon activation defines clinical severity to infant RSV infection

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About: Insufficiency in airway interferon activation defines clinical severity to infant RSV infection Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Insufficiency in airway interferon activation defines clinical severity to infant RSV infection
Creator	Wang, Lu Wang, Qian Pryhuber, Gloria Corbett, Anthony Holden-Wiltse, Jeanne »more»
source	BioRxiv; MedRxiv
abstract	Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants. Other than age at the time of infection, the causes and correlates of severe illness in infants lacking known risk factors are poorly defined. We recruited a cohort of confirmed RSV-infected infants and simultaneously assayed the presence of resident airway microbiota and the molecular status of their airways using a novel method. Rigorous statistical analyses identified a molecular airway gene expression signature of severe illness dominated by excessive chemokine expression. Global 16S rRNA sequencing confirmed an association between H. influenzae and clinical severity. Interestingly, adjusting for H. influenzae in our gene expression analysis revealed an association between severity and airway lymphocyte accumulation. Exploring the relationship between airway gene expression and the time of onset of clinical symptoms revealed a robust, acute activation of interferon (IFN) signaling, which was absent in subjects with severe illness. Finally, we explored the relationship between IFN activity, airway gene expression and productive RSV infection using a novel in vitro model of bona fide pediatric human airway epithelial cells. Interestingly, blocking IFN signaling, but not IFN ligand production, in these cells leads to increased viral infection. Our data reveal that acute airway interferon responses are physiologically relevant in the context of infant RSV infection and may be a target for therapeutic intervention. Additionally, the airway gene expression signature we define may be useful as a biomarker for efficacy of intervention responses.
has issue date	2019-05-20(xsd:dateTime)
bibo:doi	10.1101/641795
has license	medrxiv
sha1sum (hex)	6a8d26d75bd44c7666c9b7ed782c13a57f409122
schema:url	https://doi.org/10.1101/641795
resource representing a document's title	Insufficiency in airway interferon activation defines clinical severity to infant RSV infection
schema:publication	bioRxiv
resource representing a document's body	covid:6a8d26d75bd44c7666c9b7ed782c13a57f409122#body_text
is schema:about of	named entity 'dominated' named entity 'subjects' named entity 'Exploring' named entity 'IFN' named entity 'chemokine' »more»

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