Evidence map›Paper›PMID 24713657›Full record

Trial reportThe Journal of clinical investigation2014

RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction.

Rachael M Liesman, Ursula J Buchholz, Cindy L Luongo, Lijuan Yang, Alan D Proia, John P DeVincenzo, Peter L Collins, Raymond J Pickles

Open access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 1 pooled it
6.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

95 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.

  1. Frontiers in immunology · 2021
    Pooled it
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  7. RelA Signaling inInternational journal of molecular sciences · 2026
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35 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Rachael M Liesman
Ursula J Buchholz
Cindy L Luongo
Lijuan Yang
Alan D Proia
John P DeVincenzo
Peter L Collins
Raymond J Pickles
National Institutes of Health · USDuke University Hospital · USUniversity of Tennessee Health Science Center · US

Funding

Laboratory Studies of Human Respiratory Syncytial Virus and Other PneumovirusesZIAAI000372 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BUCHHOLZ, URSULA · 2009 to 2025
$21.8M
The Mucus Transport Apparatus: Why Two Layers?P50HL084934 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOUCHER, RICHARD CHARLES · 2006 to 2010
$15.6M
Molecular Biology of Viral Diseases Predoctoral Training GrantT32AI007419 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Mark T Heise, CARY A MOODY · 1993 to 2026
$4.7M
CFTR Delivery to Ciliated Airway Cells by PIV VectorsR01HL077844 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PICKLES, RAYMOND J · 2005 to 2009
$1.9M
The role of mucin-protein interactions in the innate defense of the lungR01HL103940 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KESIMER, MEHMET · 2010 to 2014
$1.8M
Why Are Steroids Ineffective at Suppressing RSV BronchiolitisR21AI103617 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PICKLES, RAYMOND J · 2013 to 2014
$407k
Howard Hughes Medical InstituteNHLBI NIH HHS P50 HL084934NHLBI NIH HHS P50HL084934NHLBI NIH HHS R01 HL077844NHLBI NIH HHS R01 HL103940NHLBI NIH HHS R01HL103940NHLBI NIH HHS R01HL77844NIAID NIH HHS R21 AI103617NIAID NIH HHS T32 AI007419NIAID NIH HHS T32AI007419
6 · The paper itself

Abstract

Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in young children. The factors that contribute to the increased propensity of RSV-induced distal airway disease compared with other commonly encountered respiratory viruses remain unclear. Here, we identified the RSV-encoded nonstructural 2 (NS2) protein as a viral genetic determinant for initiating RSV-induced distal airway obstruction. Infection of human cartilaginous airway epithelium (HAE) and a hamster model of disease with recombinant respiratory viruses revealed that NS2 promotes shedding of infected epithelial cells, resulting in two consequences of virus infection. First, epithelial cell shedding accelerated the reduction of virus titers, presumably by clearing virus-infected cells from airway mucosa. Second, epithelial cells shedding into the narrow-diameter bronchiolar airway lumens resulted in rapid accumulation of detached, pleomorphic epithelial cells, leading to acute distal airway obstruction. Together, these data indicate that RSV infection of the airway epithelium, via the action of NS2, promotes epithelial cell shedding, which not only accelerates viral clearance but also contributes to acute obstruction of the distal airways. Our results identify RSV NS2 as a contributing factor for the enhanced propensity of RSV to cause severe airway disease in young children and suggest NS2 as a potential therapeutic target for reducing the severity of distal airway disease.

Indexed as

AdolescentAdultAirway ObstructionAnimalsCell LineChildChild, PreschoolCricetinaeEpithelial CellsFemaleHumansMaleMesocricetusRespiratory MucosaRespiratory Syncytial VirusesRespiratory Syncytial Virus InfectionsNS2 protein, human respiratory syncytial virusViral Nonstructural Proteins

Identifiers

PMID24713657
PMCPMC4001550
OpenAlexW2010411959

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.