Severity of CMV Hearing Loss due to the Innate Immune Response in Mice

Abstract

Objectives:

Demonstrate the role of the innate immune response in a mouse model for Cytomegalovirus (CMV) induced sensorineural hearing loss (SNHL).

Methods:

Forty C57BL/6 and BALB/c mice underwent intracranial injection at postnatal day 3 with 200 pfu of green fluorescent protein (GFP) expressing murine (m) CMV; 10 controls received either saline or no injection. Hearing thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brain stem response testing (ABR). Temporal bones were harvested and sectioned for histologic analysis. A subset of BALB/c and C57B/6 temporal bones were harvested for histologic analysis 3 and 7 days after inoculation.

Results:

Fifty-five percent of the BALB/c mice had profound hearing loss (≥80 dB) at 4 weeks of age, while 45% initially showed moderate hearing loss that progressed to profound hearing loss by 6 weeks. The green fluorescent protein (GFP)-labeled virus was abundant in the spiral ganglion and adjacent to the scala tympani at 7 days post-injection and absent by 4 weeks. In contrast to what was seen in BALB/c mice, the C57/B6 mice showed mild hearing loss. Moreover, temporal bone histology also showed no evidence of mCMV infiltration of the cochlea 3 and 7 days post-inoculation when peak mCMV infection was expected.

Conclusions:

Since C57BL/6 mice have been shown to possess a Ly-49H receptor that triggers natural killer cell activation which is not present in BALB/c mice, these results suggest that CMV mediated hearing loss severity may be influenced by the innate immune response.