Document Type
Article
Publication Date
10-2025
Publisher
American Society for Microbiology
Source Publication
Microbiology Spectrum
Source ISSN
2165-0497
Abstract
Human cytomegalovirus (HCMV) is a prolific human herpesvirus that infects most individuals by adulthood. While typically asymptomatic in adults, congenital infection can induce serious neurological symptoms, including hearing loss, visual deficits, cognitive impairment, and microcephaly in 10%–15% of cases. HCMV has been shown to infect most neural cells, with our group recently demonstrating this capacity in stem cell-derived forebrain neurons. Infection of neurons induces deleterious effects on calcium dynamics and electrophysiological function paired with gross restructuring of neuronal morphology. Here, we utilize an induced pluripotent stem cell-derived model of the human forebrain to demonstrate how HCMV infection induces syncytia, drives neurite retraction, and remodels microtubule networks to promote viral production and release. We establish that HCMV downregulates microtubule-associated proteins while largely sparing other cytoskeletal elements. Furthermore, we pharmacologically modulate microtubule dynamics using paclitaxel (stabilize) and colchicine (destabilize) to examine the effects on neurite structure, syncytial morphology, and viral release. With paclitaxel, we found improvement of neurite outgrowth, but neither paclitaxel nor colchicine impacted viral titers. Together, these data suggest that HCMV infection-induced disruption of microtubules in human cortical neurons can be partially mitigated with microtubule stabilization, suggesting a potential avenue for future neuroprotective strategies.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Adelman, Jacob W.; Sukowaty, Andrew T.; Partridge, Kaitlyn J.; Gawrys, Jessica E.; Akins, Allison; Terhune, Scott S.; and Ebert, Allison D., "HCMV Infection of Terminally Differentiated Neurons Disrupts Microtubule Organization, Resulting in Neurite Retraction" (2025). Biological Sciences Faculty Research and Publications. 1025.
https://epublications.marquette.edu/bio_fac/1025
Comments
Published version. Microbiology Spectrum, Vol. 13, No. 11 (October 2025). DOI. © 2025 American Society for Microbiology. Used with permission.
Scott S. Terhune was affiliated with Medical College of Wisconsin at time of publication.