Evidence map›Paper›PMID 30381488›Full record

ArticleJournal of virology2019

Mutation of Influenza A Virus PA-X Decreases Pathogenicity in Chicken Embryos and Can Increase the Yield of Reassortant Candidate Vaccine Viruses.

Saira Hussain, Matthew L Turnbull, Helen M Wise, Brett W Jagger, Philippa M Beard, Kristina Kovacikova, Jeffery K Taubenberger, Lonneke Vervelde, Othmar G Engelhardt, Paul Digard

Open access · hybridAbstract read
In one paragraph

Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

17 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. PA and PA-X: two key proteins from segment 3 of the influenza viruses.Frontiers in cellular and infection microbiology · 2025
    Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Accessory Gene Products of Influenza A Virus.Cold Spring Harbor perspectives in medicine · 2021
    Review
  10. Article
  11. Article
  12. Article
  13. Article
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  15. Article
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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

10 authors at 4 institutions in 2 countries.

Saira HussainThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom.
Matthew L TurnbullThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom.
Helen M WiseThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom.
Brett W JaggerDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Philippa M BeardThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom.
Kristina KovacikovaThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom.
Jeffery K TaubenbergerNational Institutes of Health, Bethesda, Maryland, USA.
Lonneke VerveldeThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom.
Othmar G EngelhardtNational Institute for Biological Standards and Control, South Mimms, Hertfordshire, United Kingdom.
Paul DigardThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom paul.digard@roslin.ed.ac.uk.ORCID 0000-0002-0872-9440
Roslin Institute · GBNational Institutes of Health · USNational Institute for Biological Standards and Control · GBThe Pirbright Institute · GB

Funding

Influenza Viral PathogenesisZIAAI000986 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI TAUBENBERGER, JEFFERY · 2009 to 2025
$30.0M
Biotechnology and Biological Sciences Research Council BB/J01446X/1Biotechnology and Biological Sciences Research Council BB/P013740/1
6 · The paper itself

Abstract

The PA-X protein of influenza A virus has roles in host cell shutoff and viral pathogenesis. While most strains are predicted to encode PA-X, strain-dependent variations in activity have been noted. We found that PA-X protein from the A/PR/8/34 (PR8) strain had significantly lower repressive activity against cellular gene expression than PA-X proteins from the avian strains A/turkey/England/50-92/91 (H5N1) (T/E) and A/chicken/Rostock/34 (H7N1). Loss of normal PA-X expression, either by mutation of the frameshift site or by truncating the X open reading frame (ORF), had little effect on the infectious virus titer of PR8 or PR8 7:1 reassortants with T/E segment 3 grown in embryonated hens' eggs. However, in both virus backgrounds, mutation of PA-X led to decreased embryo mortality and lower overall pathology, effects that were more pronounced in the PR8 strain than in the T/E reassortant, despite the low shutoff activity of the PR8 PA-X. Purified PA-X mutant virus particles displayed an increased ratio of hemagglutinin (HA) to nucleoprotein (NP) and M1 compared to values for their wild-type (WT) counterparts, suggesting altered virion composition. When the PA-X gene was mutated in the background of poorly growing PR8 6:2 vaccine reassortant analogues containing the HA and neuraminidase (NA) segments from H1N1 2009 pandemic viruses or from an avian H7N3 strain, HA yield increased up to 2-fold. This suggests that the PR8 PA-X protein may harbor a function unrelated to host cell shutoff and that disruption of the PA-X gene has the potential to improve the HA yield of vaccine viruses.

Indexed as

MutationAnimalsChick EmbryoChickensDogsHEK293 CellsHumansInfluenza A virusInfluenza A Virus, H5N1 SubtypeInfluenza A Virus, H7N1 SubtypeInfluenza in BirdsMadin Darby Canine Kidney CellsReassortant VirusesRepressor ProteinsViral Nonstructural ProteinsPA-X protein, influenza A virusRepressor ProteinsViral Nonstructural ProteinsinfluenzaPA-Xshutoffvaccine

Identifiers

PMID30381488
PMCPMC6321911
OpenAlexW2892216701

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.