Evidence map›Paper›PMID 23135723›Full record

ArticleJournal of virology2013

Host mTORC1 signaling regulates andes virus replication.

Shannon McNulty, Mike Flint, Stuart T Nichol, Christina F Spiropoulou

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 18% 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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. COVID-19 and diabetes mellitus: how one pandemic worsens the other.Reviews in endocrine & metabolic disorders · 2020
    Review
  11. Article
  12. Drug repurposing against COVID-19: focus on anticancer agents.Journal of experimental & clinical cancer research : CR · 2020
    Review
  13. Article
  14. Hantavirus Infection Is Inhibited by Griffithsin in Cell Culture.Frontiers in cellular and infection microbiology · 2020
    Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Article
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

4 authors at 1 institution in 1 country.

Shannon McNultyViral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Mike Flint
Stuart T Nichol
Christina F Spiropoulou
Centers for Disease Control and Prevention · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hantavirus pulmonary syndrome (HPS) is a severe respiratory disease characterized by pulmonary edema, with fatality rates of 35 to 45%. Disease occurs following infection with pathogenic New World hantaviruses, such as Andes virus (ANDV), which targets lung microvascular endothelial cells. During replication, the virus scavenges 5'-m(7)G caps from cellular mRNA to ensure efficient translation of viral proteins by the host cell cap-dependent translation machinery. In cells, the mammalian target of rapamycin (mTOR) regulates the activity of host cap-dependent translation by integrating amino acid, energy, and oxygen availability signals. Since there is no approved pharmacological treatment for HPS, we investigated whether inhibitors of the mTOR pathway could reduce hantavirus infection. Here, we demonstrate that treatment with the FDA-approved rapamycin analogue temsirolimus (CCI-779) blocks ANDV protein expression and virion release but not entry into primary human microvascular endothelial cells. This effect was specific to viral proteins, as temsirolimus treatment did not block host protein synthesis. We confirmed that temsirolimus targeted host mTOR complex 1 (mTORC1) and not a viral protein, as knockdown of mTORC1 and mTORC1 activators but not mTOR complex 2 components reduced ANDV replication. Additionally, primary fibroblasts from a patient with tuberous sclerosis exhibited increased mTORC1 activity and increased ANDV protein expression, which were blocked following temsirolimus treatment. Finally, we show that ANDV glycoprotein Gn colocalized with mTOR and lysosomes in infected cells. Together, these data demonstrate that mTORC1 signaling regulates ANDV replication and suggest that the hantavirus Gn protein may modulate mTOR and lysosomal signaling during infection, thus bypassing the cellular regulation of translation.

Indexed as

Signal TransductionVirus ReplicationAntiviral AgentsCells, CulturedGene Knockdown TechniquesHumansMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesOrthohantavirusProtein Kinase InhibitorsSirolimusTOR Serine-Threonine KinasesAntiviral AgentsMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesProtein Kinase InhibitorsSirolimustemsirolimusTOR Serine-Threonine Kinases

Identifiers

PMID23135723
PMCPMC3554081
OpenAlexW2103090772

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.