Evidence map›Paper›PMID 38451085›Full record

ArticleJournal of virology2024

Human trophoblast stem cells restrict human cytomegalovirus replication.

Tyler B Rollman, Zachary W Berkebile, Hiroaki Okae, Vivian J Bardwell, Micah D Gearhart, Craig J Bierle

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

10 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Joining the dots: maternal cytomegalovirus, HIV and the placenta.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
    Review
  8. Article
  9. Article
  10. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Tyler B RollmanDivision of Pediatric Infectious Diseases, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0009-0001-7194-1540
Zachary W BerkebileDivision of Pediatric Infectious Diseases, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-9318-7470
Hiroaki OkaeDepartment of Informative Genetics, Tohoku University Graduate School of Medicine, Sendai, Japan.ORCID 0000-0002-1539-5063
Vivian J BardwellDevelopmental Biology Center, Department of Genetics, Cell Biology and Development and the Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Micah D GearhartDepartment of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-9873-1930
Craig J BierleDivision of Pediatric Infectious Diseases, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-7890-7409
University of Minnesota · USTohoku University · JP

Funding

Optimizing Immunity and Maternal Host Defense Against Congenital Cytomegalovirus InfectionR01HD098866 · NICHD · UNIVERSITY OF MINNESOTA · PI Craig John Bierle, Michael A McVoy · 2019 to 2026
$3.9M
Trophoblast development and placental susceptibility to cytomegalovirus infectionR01HD109252 · NICHD · UNIVERSITY OF MINNESOTA · PI Craig John Bierle · 2022 to 2026
$2.2M
Defining the viral determinants of cytomegalovirus transplacental transmissionR21HD087496 · NICHD · UNIVERSITY OF MINNESOTA · PI BIERLE, CRAIG JOHN · 2017 to 2018
$420k
NICHD NIH HHS R01 HD098866NICHD NIH HHS R01 HD109252NICHD NIH HHS R21 HD087496
6 · The paper itself

Abstract

Placental infection plays a central role in the pathogenesis of congenital human cytomegalovirus (HCMV) infections and is a cause of fetal growth restriction and pregnancy loss. HCMV can replicate in some trophoblast cell types, but it remains unclear how the virus evades antiviral immunity in the placenta and how infection compromises placental development and function. Human trophoblast stem cells (TSCs) can be differentiated into extravillous trophoblasts (EVTs), syncytiotrophoblasts (STBs), and organoids, and this study assessed the utility of TSCs as a model of HCMV infection in the first-trimester placenta. HCMV was found to non-productively infect TSCs, EVTs, and STBs. Immunofluorescence assays and flow cytometry experiments further revealed that infected TSCs frequently only express immediate early viral gene products. Similarly, RNA sequencing found that viral gene expression in TSCs does not follow the kinetic patterns observed during lytic infection in fibroblasts. Canonical antiviral responses were largely not observed in HCMV-infected TSCs and TSC-derived trophoblasts. Rather, infection dysregulated factors involved in cell identity, differentiation, and Wingless/Integrated signaling. Thus, while HCMV does not replicate in TSCs, infection may perturb trophoblast differentiation in ways that could interfere with placental function. IMPORTANCE: Placental infection plays a central role in human cytomegalovirus (HCMV) pathogenesis during pregnancy, but the species specificity of HCMV and the limited availability and lifespan of primary trophoblasts have been persistent barriers to understanding how infection impacts this vital organ. Human trophoblast stem cells (TSCs) represent a new approach to modeling viral infection early in placental development. This study reveals that TSCs, like other stem cell types, restrict HCMV replication. However, infection perturbs the expression of genes involved in differentiation and cell fate determination, pointing to a mechanism by which HCMV could cause placental injury.

Indexed as

CytomegalovirusStem CellsTrophoblastsVirus ReplicationCell DifferentiationCell LineageCytomegalovirus InfectionsFemaleHumansImmediate-Early ProteinsPlacentaPregnancyPregnancy Trimester, FirstImmediate-Early Proteinscongenital infectionshuman cytomegalovirusplacentatrophoblasttrophoblast stem cells

Identifiers

PMID38451085
PMCPMC11019952
OpenAlexW4392551213

What Socratic 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 Socratic graph.