Evidence map›Paper›PMID 39431915›Full record

ArticleThe Journal of general virology2024

Poxin-deficient poxviruses are sensed by cGAS prior to genome replication.

Sian Lant, Alasdair J M Hood, Joe A Holley, Ailish Ellis, Lucy Eke, Rebecca P Sumner, David O Ulaeto, Carlos Maluquer de Motes

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Article in The Journal of general virology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

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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

4 citing papers in PubMed.

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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

8 authors.

Sian LantDepartment of Microbial Sciences, University of Surrey, Guildford, GU2 7XH, UK.
Alasdair J M HoodDepartment of Microbial Sciences, University of Surrey, Guildford, GU2 7XH, UK.
Joe A HolleyDepartment of Microbial Sciences, University of Surrey, Guildford, GU2 7XH, UK.
Ailish EllisDepartment of Microbial Sciences, University of Surrey, Guildford, GU2 7XH, UK.
Lucy EkeDepartment of Microbial Sciences, University of Surrey, Guildford, GU2 7XH, UK.
Rebecca P SumnerDepartment of Microbial Sciences, University of Surrey, Guildford, GU2 7XH, UK.
David O UlaetoCBR Division, Defence Science and Technology Laboratory, Salisbury, SP4 0JQ, UK.
Carlos Maluquer de MotesDepartment of Microbial Sciences, University of Surrey, Guildford, GU2 7XH, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Poxviruses are dsDNA viruses infecting a wide range of cell types, where they need to contend with multiple host antiviral pathways, including DNA and RNA sensing. Accordingly, poxviruses encode a variety of immune antagonists, most of which are expressed early during infection from within virus cores before uncoating and genome release take place. Amongst these antagonists, the poxvirus immune nuclease (poxin) counteracts the cyclic 2'3'-GMP-AMP (2'3'-cGAMP) synthase (cGAS)/stimulator of interferon genes DNA sensing pathway by degrading the immunomodulatory cyclic dinucleotide 2'3'-cGAMP, the product of activated cGAS. Here, we use poxviruses engineered to lack poxin to investigate how virus infection triggers the activation of STING and its downstream transcription factor interferon-responsive factor 3 (IRF3). Our results demonstrate that poxin-deficient vaccinia virus (VACV) and ectromelia virus (ECTV) induce IRF3 activation in primary fibroblasts and differentiated macrophages, although to a lower extent in VACV compared to ECTV. In fibroblasts, IRF3 activation was detectable at 10 h post-infection (hpi) and was abolished by the DNA replication inhibitor cytosine arabinoside (AraC), indicating that the sensing was mediated by replicated genomes. In macrophages, IRF3 activation was detectable at 4 hpi, and this was not affected by AraC, suggesting that the sensing in this cell type was induced by genomes released from incoming virions. In agreement with this, macrophages expressing short hairpin RNA (shRNA) against the virus uncoating factor D5 showed reduced IRF3 activation upon infection. Collectively, our data show that the viral genome is sensed by cGAS prior to and during genome replication, but immune activation downstream of it is effectively suppressed by poxin. Our data also support the model where virus uncoating acts as an immune evasion strategy to simultaneously cloak the viral genome and allow the expression of early immune antagonists.

Indexed as

NucleotidyltransferasesVaccinia virusVirus ReplicationAnimalsCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNA ReplicationEctromelia virusExonucleasesFibroblastsGenome, ViralHost-Pathogen InteractionsHumansInterferon Regulatory Factor-3MacrophagesMembrane ProteinsMesocricetuscGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseExonucleasesInterferon Regulatory Factor-3IRF3 protein, humanMembrane ProteinsNucleotidyltransferasesViral ProteinscGASEctromelia virusgenome uncoatingIRF3orthopoxvirusesSTINGvaccinia virus

Identifiers

PMID39431915
PMCPMC12453400

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.