Evidence map›Paper›PMID 21307186›Full record

ArticleJournal of virology2011

The early interferon response to rotavirus is regulated by PKR and depends on MAVS/IPS-1, RIG-I, MDA-5, and IRF3.

Adrish Sen, Andrea J Pruijssers, Terence S Dermody, Adolfo García-Sastre, Harry B Greenberg

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
7.1field-weighted citation impact, top 2% 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

85 citing papers in PubMed, 141 citations in OpenAlex.

  1. How loss-of-function mutations inJournal of translational autoimmunity · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review

25 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

5 authors at 3 institutions in 1 country.

Adrish SenDepartment of Microbiology, Stanford University, Stanford, CA 94305-5101, USA.
Andrea J Pruijssers
Terence S Dermody
Adolfo García-Sastre
Harry B Greenberg
Stanford University · USVanderbilt University · USIcahn School of Medicine at Mount Sinai · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
TRANSGENIC MOUSE/ ES CELL SHARES RESOURCESP60DK020593 · NIDDK · VANDERBILT UNIVERSITY · PI MCGUINNESS, OWEN P · 1986 to 2011
$28.1M
Proteomics/GenomicsP30DK056339 · NIDDK · STANFORD UNIVERSITY · PI GREENBERG, HARRY BERNARD · 2001 to 2010
$10.4M
TRIM mediated host antiviral responses during influenza virus infectionsU19AI083025 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JUNG, JAE U · 2009 to 2013
$10.0M
BIOCHEMICAL &CHEMICAL TRAINING FOR CANCER RESEARCHT32CA009582 · NCI · VANDERBILT UNIVERSITY · PI David K Cortez · 1987 to 2026
$8.8M
VIRAL GASTROENTERITIS--BASIS OF PROTECTION AND VIRULENCER01AI021362 · NIAID · STANFORD UNIVERSITY · PI GREENBERG, HARRY BERNARD · 1989 to 2014
$5.4M
Mechanisms of Reovirus-Induced ApoptosisR01AI050080 · NIAID · VANDERBILT UNIVERSITY · PI DERMODY, TERENCE S. · 2001 to 2011
$3.0M
Function and mechanisms of reovirus-induced apoptosisF32NS071986 · NINDS · VANDERBILT UNIVERSITY · PI PRUIJSSERS, ARDINA JANNETJE · 2010 to 2012
$159k
NCI NIH HHS P30 CA068485NCI NIH HHS P30 CA68485NCI NIH HHS T32 CA009582NIAID NIH HHS R01 AI021362NIAID NIH HHS R01 AI021362-26NIAID NIH HHS R01 AI050080NIAID NIH HHS U19 AI083025NIAID NIH HHS U19AI083025NIDDK NIH HHS P30 DK056339NIDDK NIH HHS P30DK56339NIDDK NIH HHS P60 DK020593NIDDK NIH HHS P60 DK20593NINDS NIH HHS F32 NS071986
6 · The paper itself

Abstract

In mouse embryonic fibroblasts (MEFs), the bovine rotavirus (UK strain) but not the simian rhesus rotavirus (RRV) robustly triggers beta interferon (IFN-β) secretion, resulting in an IFN-dependent restriction of replication. We now find that both rotavirus strains trigger antiviral transcriptional responses early during infection and that both transcriptional responses and IFN-β secretion are completely abrogated in MAVS/IPS-1(-/-) MEFs. Replication of UK virus could be rescued in MAVS/IPS-1(-/-) MEFs, and synthesis of viral RNA significantly increased early during virus infection. UK virus induced IFN-β secretion and transcription of IFN-stimulated genes (ISGs) in both RIG-I(-/-) and MDA-5(-/-) MEFs, and neither receptor was essential by itself for the antiviral response to UK rotavirus. However, when receptors RIG-I and MDA-5 were depleted using RNA interference, we found that both contribute to the magnitude of the IFN response. IRF3 was found to be essential for MAVS/IPS-1-directed ISG transcription and IFN-β secretion during rotavirus infection. Interestingly, absence of the double-stranded RNA-dependent protein kinase PKR led to a profound defect in the capacity of host cells to secrete IFN-β in response to virus. Both PKR and IRF3 restricted the early replication of UK as indicated by significant increases in viral RNA in fibroblasts lacking either gene. Despite the loss in IFN-β secretion in PKR(-/-) MEFs, we did not observe decreased IRF3- or NF-κB-dependent early ISG transcription in these cells. Levels of transcripts encoding IFN-α4, IFN-α5, and IFN-β were high in infected PKR(-/-) MEFs, indicating that during rotavirus infection, PKR functions at a stage between IFN gene transcription and subsequent IFN-β secretion. These findings reveal that activation of the antiviral response by rotavirus is dependent on MAVS/IPS-1 and IRF3 and involves both RIG-I and MDA-5 and that IFN-β secretion during rotavirus infection is regulated by PKR.

Indexed as

Gene Expression RegulationAdaptor Proteins, Signal TransducingAnimalsDEAD Box Protein 58DEAD-box RNA HelicaseseIF-2 KinaseGene DeletionInterferon-betaInterferon-Induced Helicase, IFIH1Interferon Regulatory Factor-3MiceMice, KnockoutRotavirusAdaptor Proteins, Signal TransducingDdx58 protein, mouseDEAD Box Protein 58DEAD-box RNA HelicaseseIF-2 KinaseIfih1 protein, mouseInterferon-betaInterferon-Induced Helicase, IFIH1Interferon Regulatory Factor-3Irf3 protein, mouseMAVS protein, mouse

Identifiers

PMID21307186
PMCPMC3126121
OpenAlexW2169076520

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.