Evidence map›Paper›PMID 21734039›Full record

ArticleJournal of virology2011

Human cytomegalovirus infection maintains mTOR activity and its perinuclear localization during amino acid deprivation.

Amy J Clippinger, Tobi G Maguire, James C Alwine

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 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

41 citing papers in PubMed, 54 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Repurposing Antifungals for Host-Directed Antiviral Therapy?Pharmaceuticals (Basel, Switzerland) · 2022
    Review
  6. Article
  7. Autophagy impairment by African swine fever virus.The Journal of general virology · 2021
    Article
  8. Article
  9. Article
  10. Article
  11. Lysosomes as dynamic regulators of cell and organismal homeostasis.Nature reviews. Molecular cell biology · 2020
    Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. mTOR Senses Intracellular pH through Lysosome Dispersion from RHEB.BioEssays : news and reviews in molecular, cellular and developmental biology · 2019
    Article
  20. Common Mechanisms of Viral Injury to the Kidney.Advances in chronic kidney disease · 2019
    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 1 country.

Amy J ClippingerDepartment of Cancer Biology, 314 Biomedical Research Building, 421 Curie Blvd., School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6142, USA.
Tobi G Maguire
James C Alwine
University of Pennsylvania · USCancer Research Institute · US

Funding

Training In Tumor VirologyT32CA115299 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ROBERTSON, ERLE S. · 2006 to 2021
$4.7M
Cytomegalovirus-mediated modification of host cell metabolismR01CA157679 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ALWINE, JAMES C · 2011 to 2015
$1.6M
NCI NIH HHS R01 CA157679NCI NIH HHS R01 CA157679-01NCI NIH HHS T32 CA115299NCI NIH HHS T32CA115299-04
6 · The paper itself

Abstract

The mammalian target of rapamycin (mTOR) kinase is present in 2 functionally distinct complexes, mTOR complex 1 (mTORC1) and complex 2 (mTORC2). Active mTORC1 mediates phosphorylation of eIF4E-binding protein (4E-BP) and p70 S6 kinase (S6K), which is important for maintaining translation. During human cytomegalovirus (HCMV) infection, cellular stress responses are activated that normally inhibit mTORC1; however, previous data show that HCMV infection circumvents stress responses and maintains mTOR kinase activity. Amino acid deprivation is a stress response that normally inhibits mTORC1 activity. Amino acids can signal to mTORC1 through the Rag proteins, which promote the colocalization of mTORC1 with its activator Rheb-GTP in a perinuclear region, thereby inducing 4E-BP and S6K phosphorylation. As expected, our results show that amino acid depletion in mock-infected cells caused loss of mTORC1 activity and loss of the perinuclear localization; however, there was no loss of activity or perinuclear localization in HCMV-infected cells where the perinuclear localization of Rheb-GTP and mTOR coincided with the perinuclear assembly compartment (AC). This suggested that HCMV infection bypasses normal Rag-dependent amino acid signaling. This was demonstrated by short hairpin RNA (shRNA) depletion of Rag proteins, which had little effect on mTORC1 activity in infected cells but inhibited activity in mock-infected cells. Our data show that HCMV maintains mTORC1 activity in an amino acid- and Rag-independent manner through the colocalization of mTOR and Rheb-GTP, which occurs in association with the formation of the AC, thus bypassing inhibition that may result from lowered amino acid levels.

Indexed as

Amino AcidsCell LineCytomegalovirusCytomegalovirus InfectionsHumansTOR Serine-Threonine KinasesAmino AcidsMTOR protein, humanTOR Serine-Threonine Kinases

Identifiers

PMID21734039
PMCPMC3165763
OpenAlexW2140115339

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.