Evidence map›Paper›PMID 38538832›Full record

ArticleNature microbiology2024

FEAR antiviral response pathway is independent of interferons and countered by poxvirus proteins.

Emily A Rex, Dahee Seo, Sruthi Chappidi, Chelsea Pinkham, Sabrynna Brito Oliveira, Aaron Embry, David Heisler, Yang Liu, Moiz Munir, Karolin Luger and 5 more

Open access · greenAbstract read
In one paragraph

Article in Nature microbiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

8 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Activation and Evasion of the FEAR Pathway by RNA Viruses.bioRxiv : the preprint server for biology · 2025
    Article
  6. A year of microbiology.Nature microbiology · 2024
    Article
  7. Article
  8. Primal FEAR protects against infection.Nature microbiology · 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

15 authors at 5 institutions in 2 countries.

Emily A RexDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Dahee SeoDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Sruthi ChappidiDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Chelsea PinkhamDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Sabrynna Brito OliveiraLaboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Aaron EmbryDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
David HeislerDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yang LiuDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO, USA.
Moiz MunirDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Karolin LugerDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO, USA.ORCID http://orcid.org/0000-0001-5136-5331
Neal M AltoDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-7602-3853
Flávio Guimarães da FonsecaLaboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Robert OrchardDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-8216-4946
Dustin C HancksDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0003-2720-2545
Don B GammonDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA. don.gammon@utsouthwestern.edu.ORCID http://orcid.org/0000-0003-1144-4152
The University of Texas Southwestern Medical Center · USUniversidade Federal de Minas Gerais · BRHoward Hughes Medical Institute · USSouthwestern Medical Center · USUniversity of Colorado Boulder · US

Funding

MOLECULAR MICROBIOLOGY TRAINING GRANTT32AI007520 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI Julie K Pfeiffer · 1997 to 2026
$7.0M
Exploiting Pathogen-Encoded Immune Evasion Proteins to Uncover Evolutionarily Conserved Antiviral Host MachineryR35GM137978 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI Don Brad Gammon · 2020 to 2026
$2.5M
Evolution-guided Studies of Mitochondrial FunctionsR35GM142689 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI HANCKS, DUSTIN · 2021 to 2025
$2.0M
Overcoming host Genetic Redundancy and Pathogen Subversion to Define new host-viral InterfacesR35GM142684 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI ORCHARD, ROBERT C. · 2021 to 2025
$2.0M
Defining Arbovirus-Host Interactions Using a Novel Caenorhabditis elegans-based SystemR21AI144203 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI GAMMON, DON BRAD · 2019 to 2020
$446k
TEM for UT Southwestern Electron Microscopy Core FacilityS10OD021685 · OD · UT SOUTHWESTERN MEDICAL CENTER · PI LUBY-PHELPS, KATHERINE J · 2017 to 2017
$398k
NIAID NIH HHS R21 AI144203NIAID NIH HHS T32 AI007520NIGMS NIH HHS R35 GM137978NIGMS NIH HHS R35 GM142684NIGMS NIH HHS R35 GM142689NIH HHS S10 OD021685Welch Foundation I-2062-20210327
6 · The paper itself

Abstract

The human facilitates chromatin transcription (FACT) complex is a chromatin remodeller composed of human suppressor of Ty 16 homologue (hSpt16) and structure-specific recognition protein-1 subunits that regulates cellular gene expression. Whether FACT regulates host responses to infection remained unclear. We identify a FACT-mediated, interferon-independent, antiviral pathway that restricts poxvirus replication. Cell culture and bioinformatics approaches suggest that early viral gene expression triggers nuclear accumulation of SUMOylated hSpt16 subunits required for the expression of E26 transformation-specific sequence-1 (ETS-1)-a transcription factor that activates virus restriction programs. However, biochemical studies show that poxvirus-encoded A51R proteins block ETS-1 expression by outcompeting structure-specific recognition protein-1 binding to SUMOylated hSpt16 and by tethering SUMOylated hSpt16 to microtubules. Furthermore, A51R antagonism of FACT enhances poxvirus replication in human cells and virulence in mice. Finally, we show that FACT also restricts rhabdoviruses, flaviviruses and orthomyxoviruses, suggesting broad roles for FACT in antiviral immunity. Our study reveals the FACT-ETS-1 antiviral response (FEAR) pathway to be critical for eukaryotic antiviral immunity and describes a unique mechanism of viral immune evasion.

Indexed as

Immune EvasionInterferonsAnimalsChromatinHumansMiceChromatinInterferons

Identifiers

PMID38538832
PMCPMC11331548
OpenAlexW4393225348

What OpenQuestion holds

Textmetadata
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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.