Evidence map›Paper›PMID 25481026›Full record

ArticleVirology journal2014

The SARS coronavirus papain like protease can inhibit IRF3 at a post activation step that requires deubiquitination activity.

Krystal Matthews, Alexandra Schäfer, Alissa Pham, Matthew Frieman

Open access · goldAbstract read
In one paragraph

Article in Virology journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
1.1field-weighted citation impact, top 25% 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

40 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review
  3. Article
  4. A Method to Monitor Activity of SARS-CoV-2 Nsp3 from Cells.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Control of Innate Immune Activation by Severe Acute Respiratory Syndrome Coronavirus 2 and Other Coronaviruses.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2021
    Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. 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

4 authors at 3 institutions in 1 country.

Krystal MatthewsDepartment of Microbiology and Immunology, University of Maryland at Baltimore, 685 West Baltimore St., Room 380, Baltimore, MD, 21201, USA. kmatthews@som.umaryland.edu.
Alexandra SchäferDepartment of Epidemiology, University of North Carolina, 3304 Michael Hooker Research Building, Chapel Hill, NC, 27599, USA. aschaefe@email.unc.edu.
Alissa PhamDepartment of Microbiology, Icahn School of Medicine at Mt. Sinai, New York, NY, 10029, USA. alissapham@gmail.com.
Matthew FriemanDepartment of Microbiology and Immunology, University of Maryland at Baltimore, 685 West Baltimore St., Room 380, Baltimore, MD, 21201, USA. mfrieman@som.umaryland.edu.
University of Maryland, Baltimore · USNYU Langone Health · USUniversity of North Carolina at Chapel Hill · US

Funding

Inhibition of the Innate Immune Response by the SARS CoronavirusK22AI077797 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI FRIEMAN, MATTHEW BRYAN · 2009 to 2010
$266k
NIAID NIH HHS K22 AI077797NIAID NIH HHS K22AI077797
6 · The paper itself

Abstract

backgroundThe outcome of a viral infection is regulated by complex interactions of viral and host factors. SARS coronavirus (SARS-CoV) engages and regulates several innate immune response pathways during infection. We have previously shown that the SARS-CoV Papain-like Protease (PLpro) inhibits type I interferon (IFN) by inhibiting IRF3 phosphorylation thereby blocking downstream Interferon induction. This finding prompted us to identify other potential mechanisms of inhibition of PLpro on IFN induction.

methodsWe have used plasmids expressing PLpro and IRF3 including an IRF3 mutant that is constitutively active, called IRF3(5D). In these experiments we utilize transfections, chromatin immunoprecipitation, Electro-mobility Shift Assays (EMSA) and protein localization to identify where IRF3 and IRF3(5D) are inhibited by PLpro.

resultsHere we show that PLpro also inhibits IRF3 activation at a step after phosphorylation and that this inhibition is dependent on the de-ubiquitination (DUB) activity of PLpro. We found that PLpro is able to block the type I IFN induction of a constitutively active IRF3, but does not inhibit IRF3 dimerization, nuclear localization or DNA binding. However, inhibition of PLpro's DUB activity by mutagenesis blocked the IRF3 inhibition activity of PLpro, suggesting a role for IRF3 ubiquitination in induction of a type I IFN innate immune response.

conclusionThese results demonstrate an additional mechanism that PLpro is able to inhibit IRF3 signaling. These data suggest novel innate immune antagonism activities of PLpro that may contribute to SARS-CoV pathogenesis.

Indexed as

Cell LineChromatin ImmunoprecipitationCoronavirus 3C ProteasesCysteine EndopeptidasesElectrophoretic Mobility Shift AssayHumansInterferon Regulatory Factor-3Severe acute respiratory syndrome-related coronavirusTransfectionUbiquitinViral ProteinsCoronavirus 3C ProteasesCysteine EndopeptidasesInterferon Regulatory Factor-3IRF3 protein, humanUbiquitinViral Proteins

Identifiers

PMID25481026
PMCPMC4272517
OpenAlexW2003861830

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.