Evidence map›Paper›PMID 26716879›Full record

ArticleVirology2016

Essential role of protein kinase R antagonism by TRS1 in human cytomegalovirus replication.

Jacquelyn E Braggin, Stephanie J Child, Adam P Geballe

Abstract read
In one paragraph

Article in Virology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

18 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. RNA recognition by PKR during DNA virus infection.Journal of medical virology · 2024
    Review
  6. Antagonism of Protein Kinase R by Large DNA Viruses.Pathogens (Basel, Switzerland) · 2022
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. 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

3 authors at 2 institutions in 2 countries.

Jacquelyn E BragginDepartment of Microbiology, University of Washington Seattle, WA 98115, United States; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States. Electronic address: jbraggin@uw.edu.
Stephanie J ChildDivisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States. Electronic address: schild@fhcrc.org.
Adam P GeballeDepartment of Microbiology, University of Washington Seattle, WA 98115, United States; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States; Department of Medicine, University of Washington, Seattle, WA 98115, United States. Electronic address: ageballe@fhcrc.org.
University of Washington · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZA

Funding

TRAINING IN MOLECULAR AND CELLULAR BIOLOGYT32GM007270 · NIGMS · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 1985 to 2020
$21.0M
TRANSLATIONAL CONTROL OF CYTOMEGALOVIRUS GENE EXPRESSIONR01AI026672 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GEBALLE, ADAM P. · 1994 to 2017
$6.9M
NIAID NIH HHS R01 AI026672NIAID NIH HHS R01AI027762NIGMS NIH HHS T32 GM007270NIGMS NIH HHS T32GM007270
6 · The paper itself

Abstract

Human cytomegalovirus (HCMV) lacking TRS1 and IRS1 (HCMV[ΔI/ΔT]) cannot replicate in cell culture. Although both proteins can block the protein kinase R (PKR) pathway, they have multiple other activities and binding partners. It remains unknown which functions are essential for HCMV replication. To investigate this issue, we first identified a TRS1 mutant that is unable to bind to PKR. Like HCMV[ΔI/ΔT], a recombinant HCMV containing this mutant (HCMV[TRS1-Mut 1]) did not replicate in wild-type cells. However, HCMV[ΔI/ΔT] did replicate in cells in which PKR expression was reduced by RNA interference. Moreover, HCMV[ΔI/ΔT] and HCMV[TRS1-Mut 1] replicated to similar levels as virus containing wild-type TRS1 in cell lines in which PKR expression was knocked out by CRISPR/Cas9-mediated genome editing. These results demonstrate that the sole essential function of TRS1 is to antagonize PKR and that its other activities do not substantially enhance HCMV replication, at least in cultured human fibroblasts.

Indexed as

CytomegalovirusCytomegalovirus InfectionseIF-2 KinaseHeLa CellsHumansProtein BindingViral ProteinsVirus ReplicationeIF-2 KinaseTRS1 protein, Human herpesvirus 5Viral ProteinsCytomegalovirusDouble-stranded RNAHost defenseIRS1PKRTranslationTRS1

Identifiers

PMID26716879
PMCPMC4761322
OpenAlexW2197058601

What OpenQuestion holds

Textmetadata
LicenceTDM
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.