Evidence map›Paper›PMID 38682259›Full record

ArticleJournal of cell science2024

SARS-CoV-2 NSP5 antagonizes MHC II expression by subverting histone deacetylase 2.

Nima Taefehshokr, Alex Lac, Angela M Vrieze, Brandon H Dickson, Peter N Guo, Catherine Jung, Eoin N Blythe, Corby Fink, Amena Aktar, Jimmy D Dikeakos and 2 more

Abstract read
In one paragraph

Article in Journal of cell science, 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
–field-weighted citation impact
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.

  1. Article
  2. Article
  3. Review
  4. Article
  5. 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

12 authors.

Nima TaefehshokrDepartment of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, CanadaN6A 5C1.ORCID 0000-0001-6039-2921
Alex LacDepartment of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, CanadaN6A 5C1.
Angela M VriezeDepartment of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, CanadaN6A 5C1.
Brandon H DicksonDepartment of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, CanadaN6A 5C1.
Peter N GuoDepartment of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, CanadaN6A 5C1.
Catherine JungDepartment of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, CanadaN6A 5C1.
Eoin N BlytheDepartment of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, CanadaN6A 5C1.ORCID 0000-0002-0861-1813
Corby FinkDepartment of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, CanadaN6A 5C1.
Amena AktarDepartment of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, CanadaN6A 5C1.
Jimmy D DikeakosDepartment of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, CanadaN6A 5C1.
Gregory A DekabanDepartment of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, CanadaN6A 5C1.
Bryan HeitDepartment of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, CanadaN6A 5C1.ORCID 0000-0003-2392-468X

Funding

CIHR PJT-162203University of Western Ontario
6 · The paper itself

Abstract

SARS-CoV-2 interferes with antigen presentation by downregulating major histocompatibility complex (MHC) II on antigen-presenting cells, but the mechanism mediating this process is unelucidated. Herein, analysis of protein and gene expression in human antigen-presenting cells reveals that MHC II is downregulated by the SARS-CoV-2 main protease, NSP5. This suppression of MHC II expression occurs via decreased expression of the MHC II regulatory protein CIITA. CIITA downregulation is independent of the proteolytic activity of NSP5, and rather, NSP5 delivers HDAC2 to the transcription factor IRF3 at an IRF-binding site within the CIITA promoter. Here, HDAC2 deacetylates and inactivates the CIITA promoter. This loss of CIITA expression prevents further expression of MHC II, with this suppression alleviated by ectopic expression of CIITA or knockdown of HDAC2. These results identify a mechanism by which SARS-CoV-2 limits MHC II expression, thereby delaying or weakening the subsequent adaptive immune response.

Indexed as

Histocompatibility Antigens Class IIHistone Deacetylase 2Nuclear ProteinsPromoter Regions, GeneticSARS-CoV-2Trans-ActivatorsAntigen PresentationAntigen-Presenting CellsCoronavirus 3C ProteasesCOVID-19Cysteine EndopeptidasesDown-RegulationHEK293 CellsHumansInterferon Regulatory Factor-3Viral Nonstructural Proteins3C-like proteinase, SARS-CoV-2Coronavirus 3C ProteasesCysteine EndopeptidasesHDAC2 protein, humanHistocompatibility Antigens Class IIHistone Deacetylase 2Interferon Regulatory Factor-3IRF3 protein, humanMHC class II transactivator proteinNuclear ProteinsTrans-ActivatorsViral Nonstructural ProteinsAntigen presentationCIITADendritic cellsIRF3MacrophagesMHC IINSP5SARS-CoV-2

Identifiers

PMID38682259
PMCPMC11166459

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.