Early control of cochlear viral load limits cochlear inflammation and prevents virus-induced sensorineural hearing loss
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-induc...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-03-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-025-03416-4 |
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| Summary: | 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. |
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| ISSN: | 1742-2094 |