Early control of cochlear viral load limits cochlear inflammation and prevents virus-induced sensorineural hearing loss

Smith MD, Seleme MC, Marquez-Lago T, Chen JW, Mach M, Britt WJ (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Journal of Neuroinflammation BioMed Central

Book Volume: 22

Article Number: 92

Journal Issue: 1

DOI: 10.1186/s12974-025-03416-4

Abstract

Human cytomegalovirus (HCMV) is the most common viral infection acquired in utero and a leading cause of neurodevelopmental abnormalities, including sensorineural hearing loss (SNHL). In previous studies using a murine model of HCMV induced SNHL, hearing loss was correlated with virus-induced cochlear inflammation but not cochlear viral load. However, these previous findings were determined at the time of auditory testing, a time poiont well past critical periods of auditory development. In the current study, cochlear virus load early in auditory development could be correlated with the magnitude of virus-induced cochlear inflammation, cochlear histopathology and the development of hearing loss. Transcriptional profiling at early times after infection revealed dysregulation of multiple well described deafness-related genes (DRG). Treatment with antiviral antibodies early after infection decreased cochlear virus load, cochlear inflammation, cochlear histopathology, and normalized DRG expression arguing that virus-induced cochlear inflammation can result in pleiotropic effects on the developing auditory system. Finally, this model also demonstrated that sterilizing immunity was unnecessary for prevention of SNHL, thus providing a rationale for inteventions that could limit, but not completely prevent HCMV infection of the developing auditory system.

Authors with CRIS profile

Michael Mach Institute of Clinical and Molecular Virology

Involved external institutions

University of Alabama at Birmingham (UAB) US United States (USA) (US) Children's Hospital of Philadelphia US United States (USA) (US) Cardiology PC GB United Kingdom (GB)

How to cite

APA:

Smith, M.D., Seleme, M.C., Marquez-Lago, T., Chen, J.W., Mach, M., & Britt, W.J. (2025). Early control of cochlear viral load limits cochlear inflammation and prevents virus-induced sensorineural hearing loss. Journal of Neuroinflammation, 22(1). https://doi.org/10.1186/s12974-025-03416-4

MLA:

Smith, Matthew D., et al. "Early control of cochlear viral load limits cochlear inflammation and prevents virus-induced sensorineural hearing loss." Journal of Neuroinflammation 22.1 (2025).

BibTeX: Download