Evidence map›Paper›PMID 27907166›Full record

ArticlePLoS pathogens2016

Vaccinia Virus Protein C6 Inhibits Type I IFN Signalling in the Nucleus and Binds to the Transactivation Domain of STAT2.

Jennifer H Stuart, Rebecca P Sumner, Yongxu Lu, Joseph S Snowden, Geoffrey L Smith

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

48 citing papers in PubMed, 67 citations in OpenAlex.

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  14. A comprehensive review of monkeypox virus and mpox characteristics.Frontiers in cellular and infection microbiology · 2024
    Review
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  20. Comprehensive literature review of monkeypox.Emerging microbes & infections · 2022
    Review
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

5 authors at 1 institution in 1 country.

Jennifer H StuartDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Rebecca P SumnerDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Yongxu LuDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Joseph S SnowdenDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0001-7857-0634
Geoffrey L SmithDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0002-3730-9955
University of Cambridge · GB

Funding

Wellcome Trust 090315
6 · The paper itself

Abstract

The type I interferon (IFN) response is a crucial innate immune signalling pathway required for defense against viral infection. Accordingly, the great majority of mammalian viruses possess means to inhibit this important host immune response. Here we show that vaccinia virus (VACV) strain Western Reserve protein C6, is a dual function protein that inhibits the cellular response to type I IFNs in addition to its published function as an inhibitor of IRF-3 activation, thereby restricting type I IFN production from infected cells. Ectopic expression of C6 inhibits the induction of interferon stimulated genes (ISGs) in response to IFNα treatment at both the mRNA and protein level. C6 inhibits the IFNα-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway at a late stage, downstream of STAT1 and STAT2 phosphorylation, nuclear translocation and binding of the interferon stimulated gene factor 3 (ISGF3) complex to the interferon stimulated response element (ISRE). Mechanistically, C6 associates with the transactivation domain of STAT2 and this might explain how C6 inhibits the type I IFN signalling very late in the pathway. During virus infection C6 reduces ISRE-dependent gene expression despite the presence of the viral protein phosphatase VH1 that dephosphorylates STAT1 and STAT2. The ability of a cytoplasmic replicating virus to dampen the immune response within the nucleus, and the ability of viral immunomodulators such as C6 to inhibit multiple stages of the innate immune response by distinct mechanisms, emphasizes the intricacies of host-pathogen interactions and viral immune evasion.

Indexed as

Signal TransductionCell LineCell NucleusFlow CytometryHost-Pathogen InteractionsHumansImmunity, InnateImmunoprecipitationInterferon Type IMicroscopy, ConfocalReal-Time Polymerase Chain ReactionSTAT2 Transcription FactorTranscriptional ActivationVaccinia virusViral ProteinsInterferon Type ISTAT2 protein, humanSTAT2 Transcription FactorViral Proteins

Identifiers

PMID27907166
PMCPMC5131898
OpenAlexW2558439626

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.