Evidence map›Paper›PMID 36226985›Full record

ArticleJournal of virology2022

Levels of Influenza A Virus Defective Viral Genomes Determine Pathogenesis in the BALB/c Mouse Model.

Rebecca Penn, John S Tregoning, Katie E Flight, Laury Baillon, Rebecca Frise, Daniel H Goldhill, Cecilia Johansson, Wendy S Barclay

Open access · hybridAbstract read
In one paragraph

Article in Journal of virology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
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  8. Spatio-temporal modelling ofbioRxiv : the preprint server for biology · 2025
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  20. Quantification of influenza virus mini viral RNA dynamics using Cas13.bioRxiv : the preprint server for biology · 2024
    Article
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 1 institution in 1 country.

Rebecca PennDepartment of Infectious Disease, Imperial College Londongrid.7445.2, London, United Kingdom.ORCID 0000-0001-8449-5124
John S TregoningDepartment of Infectious Disease, Imperial College Londongrid.7445.2, London, United Kingdom.ORCID 0000-0001-8093-8741
Katie E FlightDepartment of Infectious Disease, Imperial College Londongrid.7445.2, London, United Kingdom.
Laury BaillonDepartment of Infectious Disease, Imperial College Londongrid.7445.2, London, United Kingdom.
Rebecca FriseDepartment of Infectious Disease, Imperial College Londongrid.7445.2, London, United Kingdom.
Daniel H GoldhillDepartment of Infectious Disease, Imperial College Londongrid.7445.2, London, United Kingdom.ORCID 0000-0003-4597-5963
Cecilia JohanssonNational Heart and Lung Institute, Imperial College Londongrid.7445.2, London, United Kingdom.ORCID 0000-0002-6607-5000
Wendy S BarclayDepartment of Infectious Disease, Imperial College Londongrid.7445.2, London, United Kingdom.ORCID 0000-0002-3948-0895
Imperial College London · GB

Funding

Wellcome Trust 205100/Z/16/Z
6 · The paper itself

Abstract

Defective viral genomes (DVGs), which are generated by the viral polymerase in error during RNA replication, can trigger innate immunity and are implicated in altering the clinical outcome of infection. Here, we investigated the impact of DVGs on innate immunity and pathogenicity in a BALB/c mouse model of influenza virus infection. We generated stocks of influenza viruses containing the internal genes of an H5N1 virus that contained different levels of DVGs (indicated by different genome-to-PFU ratios). In lung epithelial cells, the high-DVG stock was immunostimulatory at early time points postinfection. DVGs were amplified during virus replication in myeloid immune cells and triggered proinflammatory cytokine production. In the mouse model, infection with the different virus stocks produced divergent outcomes. The high-DVG stock induced an early type I interferon (IFN) response that limited viral replication in the lungs, resulting in minimal weight loss. In contrast, the virus stock with low levels of DVGs replicated to high titers and amplified DVGs over time, resulting in elevated levels of proinflammatory cytokines accompanied by rapid weight loss and increased morbidity and mortality. Our results suggest that the timing and levels of immunostimulatory DVGs generated during infection contribute to H5N1 pathogenesis.

Indexed as

Influenza A virusInfluenza A Virus, H5N1 SubtypeAnimalsCytokinesDefective VirusesGenome, ViralMammalsMiceMice, Inbred BALB CVirus ReplicationWeight LossCytokinesdefective viral genomesinfluenzapathogenesis

Identifiers

PMID36226985
PMCPMC9645217
OpenAlexW4304957536

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.