Cytomegalovirus-induced sensorineural hearing loss with persistent cochlear inflammation in neonatal mice
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Congenital cytomegalovirus (CMV) infection is the leading cause of sensorineural hearing loss (SNHL) in children. During murine (M)CMV-induced encephalitis, the immune response is important for both the control of viral dissemination and the clearance of virus from the brain. While the importance of CMV-induced SNHL has been described, the mechanisms surrounding its pathogenesis and the role of inflammatory responses remain unclear. This study presents a neonatal mouse model of profound SNHL in which MCMV preferentially infected both cochlear perilymphatic epithelial cells and spiral ganglion neurons. Interestingly, MCMV infection induced cochlear hair cell death by 21 days post-infection, despite a clear lack of direct infection of hair cells and the complete clearance of the virus from the cochlea by 14 dpi. Flow cytometric, immunohistochemical, and quantitative PCR analysis of MCMV-infected cochlea revealed a robust and chronic inflammatory response, including a prolonged increase in reactive oxygen species production by infiltrating macrophages. These data support a pivotal role for inflammation during MCMV-induced SNHL.
KeywordsCytomegalovirus SNHL Hearing Cochlea Inflammation Reactive oxygen species
We thank Dr. Steven Juhn and Dr. Phil Peterson for their expertise and thoughtful input. This project was supported by Award Number R01 NS-038836 from the National Institute of Neurological Disorders and Stroke, as well as a PharmacoNeuroImmunology training grant (T32DA007097) funded by the National Institute on Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS, NIDA, or the NIH.
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