Evidence map›Paper›PMID 21600055›Full record

ArticleVirology journal2011

Mutation of the elongin C binding domain of human respiratory syncytial virus non-structural protein 1 (NS1) results in degradation of NS1 and attenuation of the virus.

Claire P Straub, Wei-Har Lau, Faith M Preston, Madeleine J Headlam, Jeffery J Gorman, Peter L Collins, Kirsten M Spann

Open access · goldAbstract read
In one paragraph

Article in Virology journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.6field-weighted citation impact, top 30% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

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  15. Ubiquitination-mediated regulation of interferon responses.Growth factors (Chur, Switzerland) · 2012
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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

7 authors at 4 institutions in 2 countries.

Claire P StraubThe University of Queensland, Clinical Medical Virology Centre, QLD 4072, Australia.
Wei-Har Lau
Faith M Preston
Madeleine J Headlam
Jeffery J Gorman
Peter L Collins
Kirsten M Spann
QIMR Berghofer Medical Research Institute · AUBoston Children's Hospital · USNational Institutes of Health · USUniversity of Queensland · AU

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
Intramural NIH HHS
6 · The paper itself

Abstract

backgroundHuman respiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease in the paediatic population, immunocompromised individuals and the elderly worldwide. However, despite global efforts over the past several decades there are no commercially available vaccines. RSV encodes 2 non-structural proteins, NS1 and NS2, that are type I interferon antagonists. RSV restricts type I interferon signaling and the expression of antiviral genes by degrading STAT2. It has been proposed that NS1 binds to elongin C to form a ubiquitin ligase (E3) complex that targets STAT2 for ubiquitination and proteosomal degradation.

resultsHere, we have engineered a live recombinant RSV in which the 3 consensus amino acids of the NS1 elongin C binding domain have been replaced with alanine (NS1F-ELCmut). Mutation of this region of NS1 resulted in attenuation of RSV replication in A549 cells to levels similar to that observed when the NS1 gene is completely deleted (ΔNS1). This mutation also resulted in moderate attenuation in Vero cells. Attenuation was correlated to intracellular degradation of the mutated NS1 protein. Time course analysis showed that mutant NS1 protein accumulated in cytoplasmic bodies that contained the lysosomal marker LAMP1. However lack of cleavage of LC3 suggested that autophagy was not involved. Induction of IFN-β mRNA expression also was observed in association with the degradation of NS1 protein and attenuation of viral growth.

conclusionsThese results indicate that the elongin C binding region of NS1 is crucial for survival of the protein and that disruption of this region results in the degradation of NS1 and restriction of RSV replication.

Indexed as

Amino Acid SubstitutionAnimalsCell LineChlorocebus aethiopsElonginHumansMutant ProteinsProtein BindingRecombination, GeneticRespiratory Syncytial Virus, HumanTranscription FactorsViral Nonstructural ProteinsVirulence FactorsVirus ReplicationELOC protein, humanElonginMutant ProteinsTranscription FactorsViral Nonstructural ProteinsVirulence Factors

Identifiers

PMID21600055
PMCPMC3121706
OpenAlexW2050262336

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.