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Persistent microglial activation following neonatal CMV infection mediates neurodegeneration.

Overview

Authors: Jessica L McCord1, Debotri Chatterjee2, John Y S Han3, Drew Scoles4, Richard J Smeyne2, Nancy J Philp3, Christopher M Snyder1
ORCID iDs: Jessica L McCord, Debotri Chatterjee, John Y S Han, Drew Scoles, Richard J Smeyne, Nancy J Philp, Christopher M Snyder
  1. Department of Microbiology and Immunology, Jefferson Center for Vaccines and Pandemic Preparedness, Sidney Kimmel Medical College, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
  2. Jefferson Comprehensive Parkinson’s Center, Vickie & Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, PA, USA
  3. Department of Pathology and Genomic Medicine, Sidney Kimmel Medical College, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
  4. Department of Ophthalmology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Institutions: Thomas Jefferson University (United States); Sidney Kimmel Cancer Center (United States); Children's Hospital of Philadelphia (United States)
Journal: Science advances, volume 12, issue 11, article eadz1686
Dates: received 20 May 2025; accepted 6 February 2026; published online 11 March 2026; in print March 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1126/sciadv.adz1686 · PMID 41811959 · PMCID PMC12978234 · OpenAlex W7135035356
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), mouse (organism), other condition (population)
Methods: Statistics, Smoothing, state filtering, decompositions, Physiology & signal measures
MeSH: Cytomegalovirus*, Cytomegalovirus Infections*, Microglia*, Neurodegenerative Diseases*, Animals, Animals, Newborn, Brain, Disease Models, Animal, Humans, Mice, Muromegalovirus, Nerve Degeneration, Retina (* major topic)
Topic: Cytomegalovirus and herpesvirus research (Epidemiology, Medicine), according to OpenAlex
Funding: NIAID NIH HHS (R01 AI146235, R03 AI169437); National Eye Institute (1R01EY035772); National Institutes of Health (S10OD025128); National Institute of Allergy and Infectious Diseases (RO3AI169437, RO1AI146235)
Citations: cited by 2 papers (Europe PMC); 114 references in the paper

Abstract

Human cytomegalovirus (HCMV) causes the most common congenital viral infection in the United States, with well-known acute and late-onset neurological pathologies. Moreover, HCMV, like multiple herpesviruses, has been associated with neuroinflammation and neurodegeneration. Using a well-established neonatal murine (M)CMV infection model, we found that early-life infection drove adult-onset neuron loss and neuropathology in the retina and brain, without evident viral reactivation. Pathology was associated with the persistence of highly activated and inflammatory damage-associated microglia. Transient depletion of these microglia before the development of pathology resulted in repopulation of the tissue by microglia with a more reparative profile, which was then sustained over time. Transient microglia depletion alone was sufficient to preserve retinal structure and photoreceptor neurons, promote healing of some existing retinal damage, and preserve brain neuron density in adult infected mice. Thus, early-life infection by MCMV promoted dysfunctional and pathogenic microglia that drove adult-onset neurodegeneration in the eye and brain.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

The paper's code and data availability statement is in the Data section.

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Data

Datasets cited

Data, code, and materials availability

All data and code needed to evaluate and reproduce the results in the paper are present in the paper and/or the Supplementary Materials. No new materials were generated during the course of this study. scRNA-seq data reported in this paper are available in the Gene Expression Omnibus (GEO) database under GSE302157 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302157).

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 13 MeSH terms, 4 funders, 114 references.

Cite

This paper

McCord, J. L., Chatterjee, D., Han, J. Y. S., Scoles, D., Smeyne, R. J., Philp, N. J., & Snyder, C. M. (2026). Persistent microglial activation following neonatal CMV infection mediates neurodegeneration. Science advances, 12(11), eadz1686. https://doi.org/10.1126/sciadv.adz1686

BibTeX

@article{mccord2026persistent,
author = {McCord, Jessica L and Chatterjee, Debotri and Han, John Y S and Scoles, Drew and Smeyne, Richard J and Philp, Nancy J and Snyder, Christopher M},
title = {{Persistent microglial activation following neonatal CMV infection mediates neurodegeneration}},
journal = {Science advances},
year = {2026},
month = mar,
volume = {12},
number = {11},
pages = {eadz1686},
publisher = {American Association for the Advancement of Science},
issn = {2375-2548},
doi = {10.1126/sciadv.adz1686},
url = {https://doi.org/10.1126/sciadv.adz1686},
pmid = {41811959},
pmcid = {PMC12978234}
}

RIS

TY - JOUR
AU - McCord, Jessica L
AU - Chatterjee, Debotri
AU - Han, John Y S
AU - Scoles, Drew
AU - Smeyne, Richard J
AU - Philp, Nancy J
AU - Snyder, Christopher M
TI - Persistent microglial activation following neonatal CMV infection mediates neurodegeneration
T2 - Science advances
J2 - Sci Adv
PY - 2026
DA - 2026/03/11
VL - 12
IS - 11
SP - eadz1686
SN - 2375-2548
PB - American Association for the Advancement of Science
DO - 10.1126/sciadv.adz1686
UR - https://doi.org/10.1126/sciadv.adz1686
LA - en
ER -

CSL-JSON

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