Evidence map›Paper›PMID 24131713›Full record

ArticleJournal of virology2014

Rotavirus NSP1 protein inhibits interferon-mediated STAT1 activation.

Adrish Sen, Lusijah Rott, Nguyen Phan, Gourab Mukherjee, Harry B Greenberg

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

38 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. iScience · 2023
    Review
  5. Article
  6. Review
  7. STAT1 and Its Crucial Role in the Control of Viral Infections.International journal of molecular sciences · 2022
    Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
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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

5 authors at 2 institutions in 1 country.

Adrish SenDepartment of Microbiology and Immunology, Stanford University, Stanford, California, USA.
Lusijah Rott
Nguyen Phan
Gourab Mukherjee
Harry B Greenberg
Stanford University · USVA Palo Alto Health Care System · US

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Proteomics/GenomicsP30DK056339 · NIDDK · STANFORD UNIVERSITY · PI GREENBERG, HARRY BERNARD · 2001 to 2010
$10.4M
VIRAL GASTROENTERITIS--BASIS OF PROTECTION AND VIRULENCER01AI021362 · NIAID · STANFORD UNIVERSITY · PI GREENBERG, HARRY BERNARD · 1989 to 2014
$5.4M
NIAID NIH HHS AI057229NIAID NIH HHS R01 AI021362NIAID NIH HHS R01 AI021362-26NIAID NIH HHS U19 AI057229NIDDK NIH HHS P30 DK056339NIDDK NIH HHS P30DK56339
6 · The paper itself

Abstract

Rotavirus (RV) replicates efficiently in intestinal epithelial cells (IECs) in vivo despite the activation of a local host interferon (IFN) response. Previously, we demonstrated that homologous RV efficiently inhibits IFN induction in single infected and bystander villous IECs in vivo. Paradoxically, RV also induces significant type I IFN expression in the intestinal hematopoietic cell compartment in a relatively replication-independent manner. This suggests that RV replication and spread in IECs must occur despite exogenous stimulation of the STAT1-mediated IFN signaling pathway. Here we report that RV inhibits IFN-mediated STAT1 tyrosine 701 phosphorylation in human IECs in vitro and identify RV NSP1 as a direct inhibitor of the pathway. Infection of human HT29 IECs with simian (RRV) or porcine (SB1A or OSU) RV strains, which inhibit IFN induction by targeting either IFN regulatory factor 3 (IRF3) or NF-κB, respectively, resulted in similar regulation of IFN secretion. By flow cytometric analysis at early times during infection, neither RRV nor SB1A effectively inhibited the activation of Y701-STAT1 in response to exogenously added IFN. However, at later times during infection, both RV strains efficiently inhibited IFN-mediated STAT1 activation within virus-infected cells, indicating that RV encodes inhibitors of IFN signaling targeting STAT1 phosphorylation. Expression of RV NSP1 in the absence of other viral proteins resulted in blockage of exogenous IFN-mediated STAT1 phosphorylation, and this function was conserved in NSP1 from simian, bovine, and murine RV strains. Analysis of NSP1 determinants responsible for the inhibition of IFN induction and signaling pathways revealed that these determinants are encoded on discrete domains of NSP1. Finally, we observed that at later times during infection with SB1A, there was almost complete inhibition of IFN-mediated Y701-STAT1 in bystander cells staining negative for viral antigen. This property segregated with the NSP1 gene and was observed in a simian SA11 monoreassortant that encoded porcine OSU NSP1 but not in wild-type SA11 or a reassortant encoding simian RRV NSP1.

Indexed as

AnimalsChlorocebus aethiopsCOS CellsHT29 CellsHumansInterferon Regulatory Factor-3InterferonsNF-kappa BSignal TransductionSTAT1 Transcription FactorViral Nonstructural ProteinsInterferon Regulatory Factor-3InterferonsIRF3 protein, humanNF-kappa Bnsp1 protein, RotavirusSTAT1 protein, humanSTAT1 Transcription FactorViral Nonstructural Proteins

Identifiers

PMID24131713
PMCPMC3911692
OpenAlexW2024444641

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.