Persistent Microglial Activation Following Neonatal CMV Infection Mediates Neurodegeneration

Authors

• Jessica L. McCord, Thomas Jefferson UniversityFollow
• Debotri Chatterjee, Thomas Jefferson UniversityFollow
• John Y.S. Han, Thomas Jefferson UniversityFollow
• Drew Scoles
• Richard J. Smeyne, Thomas Jefferson UniversityFollow
• Nancy J. Philp, Thomas Jefferson UniversityFollow
• Christopher M. Snyder, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

3-13-2026

Comments

This article is the author’s final published version in Science Advances, Volume 12, Issue 11, 2026, Article number eadz1686.

The published version is available at https://doi.org/10.1126/sciadv.adz1686. Copyright © 2026 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

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.

Recommended Citation

McCord, Jessica L.; Chatterjee, Debotri; Han, John Y.S.; Scoles, Drew; Smeyne, Richard J.; Philp, Nancy J.; and Snyder, Christopher M., "Persistent Microglial Activation Following Neonatal CMV Infection Mediates Neurodegeneration" (2026). Department of Microbiology and Immunology Faculty Papers. Paper 203.
https://jdc.jefferson.edu/mifp/203

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

PubMed ID

41811959

Language

English