Evidence map›Paper›PMID 28060952›Full record

ArticlePLoS pathogens2017

TRIM25 Enhances the Antiviral Action of Zinc-Finger Antiviral Protein (ZAP).

Melody M H Li, Zerlina Lau, Pamela Cheung, Eduardo G Aguilar, William M Schneider, Leonia Bozzacco, Henrik Molina, Eugen Buehler, Akinori Takaoka, Charles M Rice and 2 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers.

0numbers the graph read from it
0cells of the map it votes in
157citing 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

157 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

97 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

12 authors.

Melody M H LiLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.ORCID 0000-0002-6905-7940
Zerlina LauIntegrated Screening Core, Experimental Therapeutics Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Pamela CheungIntegrated Screening Core, Experimental Therapeutics Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Eduardo G AguilarLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.ORCID 0000-0002-1531-1448
William M SchneiderLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Leonia BozzaccoLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Henrik MolinaProteomics Resource Center, The Rockefeller University, New York, New York, United States of America.ORCID 0000-0001-8950-4990
Eugen BuehlerTrans-NIH RNAi Screening Facility, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, Maryland, United States of America.
Akinori TakaokaDivision of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Charles M RiceLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Dan P FelsenfeldIntegrated Screening Core, Experimental Therapeutics Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Margaret R MacDonaldLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.

Funding

Transforming Translational Science and Education to Benefit Human HealthUL1TR000043 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2012 to 2015
$26.8M
Type I interferon-stimulated genes and the antiviral immune responseR01AI091707 · NIAID · ROCKEFELLER UNIVERSITY · PI RICE, CHARLES M · 2011 to 2020
$5.5M
ZAP isoforms in innate immunity-the long, the short and the extra-long of it allR01AI114873 · NIAID · ROCKEFELLER UNIVERSITY · PI MACDONALD, MARGARET R · 2015 to 2019
$1.9M
Genome wide siRNA screen for identifying host factors required for ZAP functionR03AI097089 · NIAID · ROCKEFELLER UNIVERSITY · PI MACDONALD, MARGARET R · 2012 to 2013
$188k
NCATS NIH HHS UL1 TR000043NIAID NIH HHS R01 AI091707NIAID NIH HHS R01 AI114873NIAID NIH HHS R03 AI097089
6 · The paper itself

Abstract

The host factor and interferon (IFN)-stimulated gene (ISG) product, zinc-finger antiviral protein (ZAP), inhibits a number of diverse viruses by usurping and intersecting with multiple cellular pathways. To elucidate its antiviral mechanism, we perform a loss-of-function genome-wide RNAi screen to identify cellular cofactors required for ZAP antiviral activity against the prototype alphavirus, Sindbis virus (SINV). In order to exclude off-target effects, we carry out stringent confirmatory assays to verify the top hits. Important ZAP-liaising partners identified include proteins involved in membrane ion permeability, type I IFN signaling, and post-translational protein modification. The factor contributing most to the antiviral function of ZAP is TRIM25, an E3 ubiquitin and ISG15 ligase. We demonstrate here that TRIM25 interacts with ZAP through the SPRY domain, and TRIM25 mutants lacking the RING or coiled coil domain fail to stimulate ZAP's antiviral activity, suggesting that both TRIM25 ligase activity and its ability to form oligomers are critical for its cofactor function. TRIM25 increases the modification of both the short and long ZAP isoforms by K48- and K63-linked polyubiquitin, although ubiquitination of ZAP does not directly affect its antiviral activity. However, TRIM25 is critical for ZAP's ability to inhibit translation of the incoming SINV genome. Taken together, these data uncover TRIM25 as a bona fide ZAP cofactor that leads to increased ZAP modification enhancing its translational inhibition activity.

Indexed as

Alphavirus InfectionsAnimalsAntiviral AgentsCell LineCricetinaeHEK293 CellsHumansInterferon Type IProtein DomainsProtein IsoformsRNA-Binding ProteinsRNA InterferenceRNA, Small InterferingSindbis VirusTranscription FactorsTripartite Motif ProteinsAntiviral AgentsInterferon Type IProtein IsoformsRNA-Binding ProteinsRNA, Small InterferingTranscription FactorsTRIM25 protein, humanTripartite Motif ProteinsUbiquitin-Protein LigasesZC3HAV1 protein, human

Identifiers

PMID28060952
PMCPMC5245905

What OpenQuestion holds

Textmetadata
LicenceCC0
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.