Evidence map›Paper›PMID 31217241›Full record

ArticleJournal of virology2019

Human Cytomegalovirus Disruption of Calcium Signaling in Neural Progenitor Cells and Organoids.

Samantha L Sison, Benjamin S O'Brien, Amanda J Johnson, Emily R Seminary, Scott S Terhune, Allison D Ebert

Abstract read
In one paragraph

Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

43 citing papers in PubMed, 60 citations in OpenAlex.

  1. Review
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  5. Organoids: physiologically relevantJournal of virology · 2025
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  6. Organoids: physiologically relevantJournal of virology · 2025
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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

6 authors at 1 institution in 1 country.

Samantha L SisonDepartment of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Benjamin S O'BrienDepartment of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Amanda J JohnsonDepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Emily R SeminaryDepartment of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Scott S TerhuneDepartment of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA sterhune@mcw.edu aebert@mcw.edu.
Allison D EbertDepartment of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA sterhune@mcw.edu aebert@mcw.edu.
Medical College of Wisconsin · US

Funding

Impact of HCMV proteins on viral replication and cellular signaling pathwaysR01AI083281 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI TERHUNE, SCOTT SLETTEN · 2011 to 2020
$3.2M
Cytomegalovirus manipulation of functional cortical tissue developmentR01AI132414 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI EBERT, ALLISON D, TERHUNE, SCOTT SLETTEN · 2018 to 2021
$1.9M
NIAID NIH HHS R01 AI083281NIAID NIH HHS R01 AI132414
6 · The paper itself

Abstract

The herpesvirus human cytomegalovirus (HCMV) is a leading cause of congenital birth defects. Infection can result in infants born with a variety of symptoms, including hepatosplenomegaly, microcephaly, and developmental disabilities. Microcephaly is associated with disruptions in the neural progenitor cell (NPC) population. Here, we defined the impact of HCMV infection on neural tissue development and calcium regulation, a critical activity in neural development. Regulation of intracellular calcium involves purinergic receptors and voltage-gated calcium channels (VGCC). HCMV infection compromised the ability of both pathways in NPCs as well as fibroblasts to respond to stimulation. We observed significant drops in basal calcium levels in infected NPCs which were accompanied by loss in VGCC activity and purinergic receptor responses. However, uninfected cells in the population retained responsiveness. Addition of the HCMV inhibitor maribavir reduced viral spread but failed to restore activity in infected cells. To study neural development, we infected three-dimensional cortical organoids with HCMV. Infection spread to a subset of cells over time and disrupted organoid structure, with alterations in developmental and neural layering markers. Organoid-derived infected neurons and astrocytes were unable to respond to stimulation whereas uninfected cells retained nearly normal responses. Maribavir partially restored structural features, including neural rosette formation, and dampened the impact of infection on neural cellular function. Using a tissue model system, we have demonstrated that HCMV alters cortical neural layering and disrupts calcium regulation in infected cells.

Indexed as

Calcium SignalingBenzimidazolesCell DifferentiationCell LineCytomegalovirusCytomegalovirus InfectionsDichlororibofuranosylbenzimidazoleHumansInduced Pluripotent Stem CellsNeural Stem CellsOrgan Culture TechniquesOrganoidsReceptors, PurinergicRibonucleosidesVirus ReplicationVoltage-Gated Sodium ChannelsBenzimidazolesDichlororibofuranosylbenzimidazolemaribavirReceptors, PurinergicRibonucleosidesVoltage-Gated Sodium Channelsastrocytescalcium signalingcytomegalovirusmaribavirmicrocephalyneural stem cellsneuronsorganoids

Identifiers

PMID31217241
PMCPMC6694809
OpenAlexW2951350064

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.