Evidence map›Paper›PMID 36695568›Full record

ArticleeLife2023

A concerted mechanism involving ACAT and SREBPs by which oxysterols deplete accessible cholesterol to restrict microbial infection.

David B Heisler, Kristen A Johnson, Duo H Ma, Maikke B Ohlson, Lishu Zhang, Michelle Tran, Chase D Corley, Michael E Abrams, Jeffrey G McDonald, John W Schoggins and 2 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
10.8field-weighted citation impact, top 1% 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

25 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Visualization of the interaction between sphingomyelin and cholesterol in lipid bilayer membranes.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025
    Review
  11. mBio · 2025
    Article
  12. Article
  13. Review
  14. Monitoring Accessible Cholesterol Levels in Immune Cells.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. 25-Hydroxycholesterol in health and diseases.Journal of lipid research · 2024
    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

12 authors at 1 institution in 1 country.

David B Heisler *Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, United States.ORCID https://orcid.org/0000-0002-6482-4215
Kristen A Johnson *Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, United States.ORCID https://orcid.org/0000-0003-2635-7406
Duo H MaDepartment of Microbiology, The University of Texas Southwestern Medical Center, Dallas, United States.ORCID https://orcid.org/0000-0002-6736-551X
Maikke B OhlsonDepartment of Microbiology, The University of Texas Southwestern Medical Center, Dallas, United States.
Lishu ZhangDepartment of Microbiology, The University of Texas Southwestern Medical Center, Dallas, United States.
Michelle TranDepartment of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, United States.
Chase D CorleyDepartment of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, United States.
Michael E AbramsDepartment of Microbiology, The University of Texas Southwestern Medical Center, Dallas, United States.
Jeffrey G McDonaldDepartment of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, United States.
John W SchogginsDepartment of Microbiology, The University of Texas Southwestern Medical Center, Dallas, United States.ORCID https://orcid.org/0000-0002-7944-6800
Neal M AltoDepartment of Microbiology, The University of Texas Southwestern Medical Center, Dallas, United States.ORCID https://orcid.org/0000-0002-7602-3853
Arun RadhakrishnanDepartment of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, United States.ORCID https://orcid.org/0000-0002-7266-7336
The University of Texas Southwestern Medical Center · US

Funding

Tissue Culture & Antibody Production CoreP01HL160487 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI Helen Haskell Hobbs · 2022 to 2026
$14.9M
UT Southwestern NORCP30DK127984 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI Jeff G McDonald · 2022 to 2026
$7.4M
MOLECULAR MICROBIOLOGY TRAINING GRANTT32AI007520 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI Julie K Pfeiffer · 1997 to 2026
$7.0M
Type III effector regulation of host signal transduction systemsR01AI083359 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI ALTO, NEAL MATHEW · 2009 to 2024
$6.3M
A functional evolutionary genetic approach to combat viral infectionDP1AI158124 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI SCHOGGINS, JOHN W. · 2020 to 2024
$5.7M
Oxysterol Regulation of Microbial PathogenesisR01AI158357 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI ALTO, NEAL MATHEW, RADHAKRISHNAN, ARUN · 2021 to 2025
$2.9M
Type III effector regulation of host GTPase signalingR56AI083359 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI ALTO, NEAL MATHEW · 2014 to 2014
$452k
NHLBI NIH HHS P01 HL160487NIAID NIH HHS DP1 AI158124NIAID NIH HHS R01 AI083359NIAID NIH HHS R01 AI158357NIAID NIH HHS R56 AI083359NIAID NIH HHS T32 AI007520NIDDK NIH HHS P30 DK127984NIH HHS 5T32AI007520NIH HHS AI083359NIH HHS AI158124NIH HHS AI158357NIH HHS HL160487
6 · The paper itself

Abstract

Most of the cholesterol in the plasma membranes (PMs) of animal cells is sequestered through interactions with phospholipids and transmembrane domains of proteins. However, as cholesterol concentration rises above the PM's sequestration capacity, a new pool of cholesterol, called accessible cholesterol, emerges. The transport of accessible cholesterol between the PM and the endoplasmic reticulum (ER) is critical to maintain cholesterol homeostasis. This pathway has also been implicated in the suppression of both bacterial and viral pathogens by immunomodulatory oxysterols. Here, we describe a mechanism of depletion of accessible cholesterol from PMs by the oxysterol 25-hydroxycholesterol (25HC). We show that 25HC-mediated activation of acyl coenzyme A: cholesterol acyltransferase (ACAT) in the ER creates an imbalance in the equilibrium distribution of accessible cholesterol between the ER and PM. This imbalance triggers the rapid internalization of accessible cholesterol from the PM, and this depletion is sustained for long periods of time through 25HC-mediated suppression of SREBPs and continued activation of ACAT. In support of a physiological role for this mechanism, 25HC failed to suppress Zika virus and human coronavirus infection in ACAT-deficient cells, and

Indexed as

OxysterolsZika VirusZika Virus InfectionAcyltransferasesAnimalsBacteriaCell MembraneCholesterolHumansMiceAcyltransferasesCholesterolOxysterolscell biologycoronavirusendoplasmic reticulumListeria monocytogenesmouseplasma membranevirusesZika virus

Identifiers

PMID36695568
PMCPMC9925056
OpenAlexW4317939786

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.