HCMV immediate-early protein IE2 induces neurotoxicity and hearing loss by disrupting TSC2-mTOR signaling and metabolic homeostasis.

ABSTRACT: Sensorineural hearing loss (SNHL) caused by human cytomegalovirus (HCMV) infection involves alterations in both the central auditory pathways and cochlear structures. Immediate early (IE) proteins are critical for HCMV pathogenicity and have been associated with neurodevelopmental disorders; however, their contribution to HCMV-associated SNHL remains unclear. Here, we generated transgenic mouse models expressing HCMV IE1 and IE2 protein to investigate their effects on auditory function and cochlear pathology. Auditory brainstem response (ABR) measurements revealed that expression of IE2, but not IE1, led to significantly elevated ABR thresholds and impaired auditory processing. IE2-transgenic mice exhibited synaptic loss, hair cell degeneration, and neuronal atrophy in auditory regions. sc

SUBMITTER: Yu M 

PROVIDER: S-EPMC12777122 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature