Evidence map›Paper›PMID 38461415›Full record

ArticleCell reports2024

HDAC5 enhances IRF3 activation and is targeted for degradation by protein C6 from orthopoxviruses including Monkeypox virus and Variola virus.

Yongxu Lu, Yiqi Zhao, Chen Gao, Shreehari Suresh, Jinghao Men, Amelia Sawyers, Geoffrey L Smith

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 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

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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

7 authors at 3 institutions in 2 countries.

Yongxu LuDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK; Chinese Academy of Medical Sciences-Oxford Institute, University of Oxford, Oxford, UK. Electronic address: yongxu.lu@path.ox.ac.uk.
Yiqi ZhaoDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK; Chinese Academy of Medical Sciences-Oxford Institute, University of Oxford, Oxford, UK.
Chen GaoDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Shreehari SureshDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Jinghao MenDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Amelia SawyersDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Geoffrey L SmithDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK; The Pirbright Institute, Surrey, UK; Chinese Academy of Medical Sciences-Oxford Institute, University of Oxford, Oxford, UK. Electronic address: geoffrey.smith@path.ox.ac.uk.
University of Cambridge · GBChinese Academy of Medical Sciences & Peking Union Medical College · CNUniversity of Oxford · GB

Funding

Research Training in Pediatric OncologyT32CA136432 · NCI · DANA-FARBER CANCER INST · PI SCOTT A ARMSTRONG · 2009 to 2026
$7.9M
NCI NIH HHS T32 CA136432Wellcome Trust
6 · The paper itself

Abstract

Histone deacetylases (HDACs) regulate gene expression and innate immunity. Previously, we showed that HDAC5 is degraded during Vaccinia virus (VACV) infection and is a restriction factor for VACV and herpes simplex virus type 1. Here, we report that HDAC5 promotes interferon regulatory factor 3 (IRF3) activation downstream of Toll-IL-1 receptor (TIR) domain-containing adaptor molecule-1 or Sendai virus-mediated stimulation without requiring HDAC activity. Loss of HDAC5-mediated IRF3 activation is restored by re-introduction of HDAC5 but not HDAC1 or HDAC4. The antiviral activity of HDAC5 is antagonized by VACV protein C6 and orthologs from the orthopoxviruses cowpox, rabbitpox, camelpox, monkeypox, and variola. Infection by many of these viruses induces proteasomal degradation of HDAC5, and expression of C6 alone can induce HDAC5 degradation. Mechanistically, C6 binds to the dimerization domain of HDAC5 and prevents homodimerization and heterodimerization with HDAC4. Overall, this study describes HDAC5 as a positive regulator of IRF3 activation and provides mechanistic insight into how the poxviral protein C6 binds to HDAC5 to antagonize its function.

Indexed as

OrthopoxvirusVariola virusHistone DeacetylasesInterferon Regulatory Factor-3Monkeypox virusVaccinia virusHistone DeacetylasesInterferon Regulatory Factor-3CP: MicrobiologyHDAC4HDAC5immune evasionInnate immunityIRF3monkeypox virusproteasome-mediated degradationprotein C6vaccinia virusvariola virus

Identifiers

PMID38461415
PMCPMC11650635
OpenAlexW4392764379

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.