Evidence map›Paper›PMID 40781068›Full record

ArticleNature communications2025

Human cytomegalovirus induces neuronal gene expression through IE1 for viral maturation.

Laurel E Kelnhofer-Millevolte, Julian R Smith, Daniel H Nguyen, Lea S Wilson, Hannah C Lewis, Edward A Arnold, Mia R Brinkley, Kihye Shin, Jin-Hyun Ahn, Eui Tae Kim and 4 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. A comprehensive method for quantifying human cytomegalovirus plaque assays.Frontiers in cellular and infection microbiology · 2026
    Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Laurel E Kelnhofer-MillevolteHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Julian R SmithHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Daniel H NguyenHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0009-0006-0431-9088
Lea S WilsonHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0009-0005-6531-3723
Hannah C LewisHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Edward A ArnoldHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Mia R BrinkleyHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Kihye ShinDepartment of Microbiology and Immunology, Jeju National University College of Medicine, Jeju, Republic of Korea.ORCID http://orcid.org/0000-0001-8044-4530
Jin-Hyun AhnDepartment of Microbiology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.ORCID http://orcid.org/0000-0002-9545-9062
Eui Tae KimDepartment of Microbiology and Immunology, Jeju National University College of Medicine, Jeju, Republic of Korea.ORCID http://orcid.org/0000-0002-1631-3197
Katarzyna KulejTow Center for Developmental Oncology, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Adam P GeballeHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-9279-6653
Srinivas RamachandranRNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO, USA.ORCID http://orcid.org/0000-0003-2929-1377
Daphne C AvgoustiHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. dxa1388@miami.edu.ORCID http://orcid.org/0000-0002-1700-3959

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
Diseases of Public Health Importance Training GrantT32AI007509 · NIAID · UNIVERSITY OF WASHINGTON · PI LUND, JENNIFER M · 1997 to 2024
$6.3M
University of Washington Medical Scientist Training ProgramT32GM153182 · NIGMS · UNIVERSITY OF WASHINGTON · PI MARSHALL S. HORWITZ · 2024 to 2026
$5.3M
Investigating chromatin mechanisms using viral systemsR35GM133441 · NIGMS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Daphne Christina Avgousti · 2019 to 2026
$3.8M
Viral Pathogenesis Training ProgramT32AI083203 · NIAID · UNIVERSITY OF WASHINGTON · PI BLOOM, JESSE D, LAGUNOFF, MICHAEL · 2009 to 2023
$2.7M
Maintenance of cellular memory through replicationR35GM133434 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI RAMACHANDRAN, SRINIVAS · 2019 to 2023
$2.0M
Evolution and mechanisms of cytomegalovirus antagonism of host cell defensesR01AI145945 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GEBALLE, ADAM P. · 2020 to 2023
$1.8M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA015704NIAID NIH HHS R01 AI145945NIAID NIH HHS T32 AI007509NIAID NIH HHS T32 AI083203NIGMS NIH HHS R35 GM133434NIGMS NIH HHS R35 GM133441NIGMS NIH HHS T32 GM153182U.S. Department of Health & Human Services | National Institutes of Health (NIH) AI145945U.S. Department of Health & Human Services | National Institutes of Health (NIH) GM133434U.S. Department of Health & Human Services | National Institutes of Health (NIH) GM133441
6 · The paper itself

Abstract

Viral invasion of the host cell causes some of the most dramatic changes in biology. Human cytomegalovirus (HCMV) extensively remodels host cells, altering nuclear shape and generating a cytoplasmic viral-induced assembly compartment (vIAC). How these striking morphology changes occur in the context of host gene regulation is still emerging. Histone variant macroH2A1 is both important for maintaining nuclear integrity and functions to promote herpes simplex virus infection. Therefore, we hypothesized it may also function in cytomegalovirus infection. Here, we discovered that macroH2A1 is necessary for HCMV-induced cellular reorganization and formation of infectious progeny. Using RNA-seq in infected cells, we find that while all viral genes are highly expressed in the absence of macroH2A1, many HCMV-induced host genes are not. Remarkably, hundreds of these HCMV-induced macroH2A1-dependent host genes are associated with a neuronal signature. Further, we find that HCMV immediate early protein, IE1, is both necessary and sufficient to induce these neuronal genes, providing a mechanism of activation. Together, our findings demonstrate that HCMV hijacks a dormant neuronal secretory pathway through chromatin manipulation for efficient virion maturation.

Indexed as

CytomegalovirusCytomegalovirus InfectionsImmediate-Early ProteinsNeuronsVirus AssemblyGene Expression RegulationHistonesHost-Pathogen InteractionsHumansHistonesIE1 protein, cytomegalovirusImmediate-Early Proteins

Identifiers

PMID40781068
PMCPMC12334593

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.