Evidence map›Paper›PMID 29073079›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

Inhibition of DAI-dependent necroptosis by the Z-DNA binding domain of the vaccinia virus innate immune evasion protein, E3.

Heather Koehler, Samantha Cotsmire, Jeffrey Langland, Karen V Kibler, Daniel Kalman, Jason W Upton, Edward S Mocarski, Bertram L Jacobs

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

111 citing papers in PubMed, 143 citations in OpenAlex.

  1. Review
  2. Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026
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51 more citing papers are in PubMed but not listed here.

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 3 institutions in 1 country.

Heather KoehlerCenter for Immunotherapy, Vaccines, and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287.
Samantha CotsmireCenter for Immunotherapy, Vaccines, and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287.
Jeffrey LanglandCenter for Immunotherapy, Vaccines, and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287.
Karen V KiblerCenter for Immunotherapy, Vaccines, and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287.
Daniel KalmanDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322.
Jason W UptonDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712.
Edward S MocarskiDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.
Bertram L JacobsCenter for Immunotherapy, Vaccines, and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287; bjacobs@asu.edu.ORCID 0000-0002-9529-8107
Arizona State University · USEmory University · USThe University of Texas at Austin · US

Funding

Monkeypox virus, Interferon, and NecroptosisR01AI095394 · NIAID · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI JACOBS, BERTRAM L. · 2012 to 2024
$4.9M
Bacterial factors modulating host immunityR01DK074731 · NIDDK · EMORY UNIVERSITY · PI KALMAN, DANIEL · 2008 to 2018
$2.4M
Innate activation and death signals in health and diseaseR01AI118853 · NIAID · EMORY UNIVERSITY · PI EDWARD S MOCARSKI, EDWARD S. · 2015 to 2018
$1.7M
NIAID NIH HHS R01 AI095394NIAID NIH HHS R01 AI118853NIDDK NIH HHS R01 DK074731
6 · The paper itself

Abstract

Vaccinia virus (VACV) encodes an innate immune evasion protein, E3, which contains an N-terminal Z-nucleic acid binding (Zα) domain that is critical for pathogenicity in mice. Here we demonstrate that the N terminus of E3 is necessary to inhibit an IFN-primed virus-induced necroptosis. VACV deleted of the Zα domain of E3 (VACV-E3LΔ83N) induced rapid RIPK3-dependent cell death in IFN-treated L929 cells. Cell death was inhibited by the RIPK3 inhibitor, GSK872, and infection with this mutant virus led to phosphorylation and aggregation of MLKL, the executioner of necroptosis. In 293T cells, induction of necroptosis depended on expression of RIPK3 as well as the host-encoded Zα domain-containing DNA sensor, DAI. VACV-E3LΔ83N is attenuated in vivo, and pathogenicity was restored in either RIPK3- or DAI-deficient mice. These data demonstrate that the N terminus of the VACV E3 protein prevents DAI-mediated induction of necroptosis.

Indexed as

AnimalsCaspasesCell DeathCell LineCell SurvivalDNA, Z-FormGlycoproteinsHumansImmunity, InnateInterferon Type IMiceProtein DomainsReceptor-Interacting Protein Serine-Threonine KinasesRNA-Binding ProteinsVaccinia virusViral ProteinsCaspasesDNA, Z-FormE3L protein, Vaccinia virusGlycoproteinsInterferon Type IReceptor-Interacting Protein Serine-Threonine KinasesRipk3 protein, mouseRNA-Binding ProteinsViral ProteinsZbp1 protein, mousenecroptosisRIPK3type 1 interferonvacciniaZ-DNA binding domain

Identifiers

PMID29073079
PMCPMC5664489
OpenAlexW2762118399

What OpenQuestion holds

Textmetadata
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.