Evidence map›Paper›PMID 22291597›Full record

ArticlePLoS pathogens2012

HCMV targets the metabolic stress response through activation of AMPK whose activity is important for viral replication.

Jessica McArdle, Nathaniel J Moorman, Joshua Munger

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

78 citing papers in PubMed, 118 citations in OpenAlex.

  1. Article
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  11. Targeting AMP-activated protein kinase in sepsis.Frontiers in endocrinology · 2024
    Review
  12. Abnormal glucose metabolism in virus associated sepsis.Frontiers in cellular and infection microbiology · 2023
    Review
  13. Article
  14. Human cytomegalovirus induces neuronal enolase to support virally mediated metabolic remodeling.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  15. Article
  16. Article
  17. Article
  18. Review
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18 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

3 authors at 2 institutions in 1 country.

Jessica McArdleDepartment of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York, United States of America.
Nathaniel J Moorman
Joshua Munger
University of Rochester Medical Center · USUniversity of North Carolina at Chapel Hill · US

Funding

Training in HIV Replication and PathogenesisT32AI049815 · NIAID · UNIVERSITY OF ROCHESTER · PI WEDEKIND, JOSEPH E · 2001 to 2020
$3.5M
Metabolic regulatory mechanisms essential for Human Cytomegalovirus replicationR01AI081773 · NIAID · UNIVERSITY OF ROCHESTER · PI MUNGER, JOSHUA C · 2010 to 2014
$1.7M
Metabolic regulatory mechanisms essential for Human Cytomegalovirus replicationR56AI081773 · NIAID · UNIVERSITY OF ROCHESTER · PI MUNGER, JOSHUA C · 2015 to 2015
$384k
NIAID NIH HHS R01 AI081773NIAID NIH HHS R01AI081773NIAID NIH HHS R56 AI081773NIAID NIH HHS T32 AI049815
6 · The paper itself

Abstract

Human Cytomegalovirus (HCMV) infection induces several metabolic activities that have been found to be important for viral replication. The cellular AMP-activated protein kinase (AMPK) is a metabolic stress response kinase that regulates both energy-producing catabolic processes and energy-consuming anabolic processes. Here we explore the role AMPK plays in generating an environment conducive to HCMV replication. We find that HCMV infection induces AMPK activity, resulting in the phosphorylation and increased abundance of several targets downstream of activated AMPK. Pharmacological and RNA-based inhibition of AMPK blocked the glycolytic activation induced by HCMV-infection, but had little impact on the glycolytic pathway of uninfected cells. Furthermore, inhibition of AMPK severely attenuated HCMV replication suggesting that AMPK is an important cellular factor for HCMV replication. Inhibition of AMPK attenuated early and late gene expression as well as viral DNA synthesis, but had no detectable impact on immediate-early gene expression, suggesting that AMPK activity is important at the immediate early to early transition of viral gene expression. Lastly, we find that inhibition of the Ca²⁺-calmodulin-dependent kinase kinase (CaMKK), a kinase known to activate AMPK, blocks HCMV-mediated AMPK activation. The combined data suggest a model in which HCMV activates AMPK through CaMKK, and depends on their activation for high titer replication, likely through induction of a metabolic environment conducive to viral replication.

Indexed as

GlycolysisStress, PhysiologicalVirus ReplicationAMP-Activated Protein Kinase KinasesCalcium-Calmodulin-Dependent Protein Kinase KinaseCell LineCytomegalovirusCytomegalovirus InfectionsDNA, ViralEnzyme ActivationGene Expression Regulation, ViralHumansProtein KinasesAMP-Activated Protein Kinase KinasesCalcium-Calmodulin-Dependent Protein Kinase KinaseDNA, ViralProtein Kinases

Identifiers

PMID22291597
PMCPMC3266935
OpenAlexW2014255712

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.