Evidence map›Paper›PMID 38652659›Full record

ArticleCell reports2024

HSV-1 employs UL56 to antagonize expression and function of cGAMP channels.

Henry T W Blest, Alexander Redmond, Jed Avissar, Jake Barker, Anne Bridgeman, Gerissa Fowler, Lise Chauveau, Jonny Hertzog, Iolanda Vendrell, Roman Fischer and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

10 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Monkeypox virus protein OPG188 antagonizes cGAS-STING antiviral signaling pathway to mediate immune evasion.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Vaccines · 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

17 authors at 5 institutions in 4 countries.

Henry T W BlestMedical Research Council Translational Immune Discovery Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, OX3 9DS Oxford, UK.
Alexander RedmondMedical Research Council Translational Immune Discovery Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, OX3 9DS Oxford, UK.
Jed AvissarMedical Research Council Translational Immune Discovery Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, OX3 9DS Oxford, UK.
Jake BarkerDepartment of Pathology, University of Cambridge, CB2 1QP Cambridge, UK.
Anne BridgemanMedical Research Council Translational Immune Discovery Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, OX3 9DS Oxford, UK.
Gerissa FowlerMedical Research Council Translational Immune Discovery Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, OX3 9DS Oxford, UK.
Lise ChauveauMedical Research Council Translational Immune Discovery Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, OX3 9DS Oxford, UK.
Jonny HertzogMedical Research Council Translational Immune Discovery Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, OX3 9DS Oxford, UK.
Iolanda VendrellTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Roman FischerTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Marie B IversenDepartment of Biomedicine, Aarhus University, Aarhus Aarhus C, Denmark.
Lichen JingDepartment of Medicine, University of Washington, Seattle, WA 98195, USA.
David M KoelleDepartment of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA; Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA; Benaroya Research Institute, Seattle, WA 98101, USA.
Søren R PaludanDepartment of Biomedicine, Aarhus University, Aarhus Aarhus C, Denmark.
Benedikt M KesslerTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Colin M CrumpDepartment of Pathology, University of Cambridge, CB2 1QP Cambridge, UK.
Jan RehwinkelMedical Research Council Translational Immune Discovery Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, OX3 9DS Oxford, UK. Electronic address: jan.rehwinkel@imm.ox.ac.uk.
University of Oxford · GBChinese Academy of Medical Sciences & Peking Union Medical College · CNAarhus University · DKUniversity of Cambridge · GBUniversity of Washington · US

Funding

Large Scale T Cell Epitope Discovery: Local and Systemic T cell Response to Herpes Simplex Virus75N93019C00063 · NIAID · UNIVERSITY OF WASHINGTON · PI MYER, TIM · 2019 to 2023
$5.5M
Genomic systems approach to measure HSV-1-specific T-cell dominance in humansR01AI094019 · NIAID · UNIVERSITY OF WASHINGTON · PI KOELLE, DAVID M · 2012 to 2016
$1.9M
European Research Council 786602Medical Research Council MC_UU_00008/8NIAID NIH HHS 75N93019C00063NIAID NIH HHS R01 AI094019Wellcome Trust 100954
6 · The paper itself

Abstract

DNA sensing is important for antiviral immunity. The DNA sensor cGAS synthesizes 2'3'-cyclic GMP-AMP (cGAMP), a second messenger that activates STING, which induces innate immunity. cGAMP not only activates STING in the cell where it is produced but cGAMP also transfers to other cells. Transporters, channels, and pores (including SLC19A1, SLC46A2, P2X7, ABCC1, and volume-regulated anion channels (VRACs)) release cGAMP into the extracellular space and/or import cGAMP. We report that infection with multiple human viruses depletes some of these cGAMP conduits. This includes herpes simplex virus 1 (HSV-1) that targets SLC46A2, P2X7, and the VRAC subunits LRRC8A and LRRC8C for degradation. The HSV-1 protein UL56 is necessary and sufficient for these effects that are mediated at least partially by proteasomal turnover. UL56 thereby inhibits cGAMP uptake via VRAC, SLC46A2, and P2X7. Taken together, HSV-1 antagonizes intercellular cGAMP transfer. We propose that this limits innate immunity by reducing cell-to-cell communication via the immunotransmitter cGAMP.

Indexed as

Herpesvirus 1, HumanNucleotides, CyclicAnimalsHEK293 CellsHerpes SimplexHumansViral Proteinscyclic guanosine monophosphate-adenosine monophosphateNucleotides, CyclicUL56 protein, Human herpesvirus 1Viral ProteinscGAMPcGAMP transportCP: ImmunologyCP: MicrobiologyDNA sensingherpes simplex virusLRRC8AP2X7SLC46A2STINGUL56VRAC

Identifiers

PMID38652659
PMCPMC7617956
OpenAlexW4395020725

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.