NIH grant: Immune Mechanisms of Cochlear Injury in Congenital Cytomegalovirus Infection (1K08DC023954-01)

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NIH grant 1K08DC023954-01: Immune Mechanisms of Cochlear Injury in Congenital Cytomegalovirus Infection
Institute: {'code': 'DC', 'abbreviation': 'NIDCD', 'name': 'National Institute on Deafness and Other Communication Disorders', 'admin_org_id': '12500019', 'admin_funding_url': ''}. PI: Grace SOON Kim. Award: $196992.
Start: 2026-07-10T00:00:00.
PROJECT SUMMARY
Congenital cytomegalovirus (CMV) infection is the leading non-genetic cause of sensorineural hearing loss in
children, affecting approximately one in 200 live births worldwide. Despite this high prevalence, the mechanisms
linking CMV infection to auditory injury remain poorly understood, and no existing therapy reliably prevents
hearing loss. Evidence from neonatal murine models suggests that immune-mediated inflammation contributes
significantly to cochlear damage, yet the specific pathways remain undefined. Natural killer (NK) cells – early
innate responders critical for controlling CMV – release interferon gamma (IFN-), a cytokine essential for
antiviral defense but also capable of causing collateral tissue injury in sensitive organs such as the cochlea.
This proposal investigates how NK cells and IFN- contribute to cochlear inflammation and hearing loss during
congenital CMV infection. Using a neonatal murine CMV (MCMV) model, Aim 1 will define the timing and extent
of NK cell infiltration, cytokine production, and auditory injury. Aim 2 will determine whether NK cells are required
for this pathology using complementary depletion models that assess effects on inflammation, cochlear structure,
and hearing function. Aim 3 will identify how IFN- signaling independent of NK cells alters the health of cochlear
cells and test whether pharmacologic inhibition of this pathway can prevent auditory injury.
This work bridges viral immunology and auditory neuroscience to uncover the mechanisms by which antiviral
immune responses contribute to congenital hearing loss. Findings will establish a foundation for future studies
dissecting the molecular mechanisms of cochlear injury and for developing targeted immunomodulatory
strategies to preserve hearing in affected infants. The proposed research directly aligns with the NIDCD mission
to understand, treat, and prevent disorders of hearing and communication.

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