Virus-induced cochlear inflammation in newborn mice alters auditory function
Cathy Yea Won Sung, … , Keiko Hirose, William Britt
Cathy Yea Won Sung, … , Keiko Hirose, William Britt
Published September 5, 2019
Citation Information: JCI Insight. 2019;4(17):e128878. https://doi.org/10.1172/jci.insight.128878.
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Research Article Inflammation Otology

Virus-induced cochlear inflammation in newborn mice alters auditory function

Abstract

Although human cytomegalovirus (HCMV) is a known cause of sensorineural hearing loss in infants with congenital HCMV (cCMV) infections, mechanisms that contribute to sensorineural hearing loss (SNHL) in infants with cCMV infection are not well defined. Using a murine model of CMV infection during auditory development, we have shown that peripheral infection of newborn mice with murine CMV (MCMV) results in focal infection of the cochlea and virus-induced cochlear inflammation. Approximately 50%–60% of infected mice exhibited increased auditory brainstem response (ABR) thresholds across a range of sound frequencies. Histological analyses of the cochlea in MCMV-infected mice with elevated ABR thresholds revealed preservation of hair cell (HC) number and morphology in the organ of Corti. In contrast, the number of spiral ganglion neurons (SGN), synapses, and neurites connecting the cochlear HC and SGN nerve terminals were decreased. Decreasing cochlear inflammation by corticosteroid treatment of MCMV-infected mice resulted in preservation of SGN and improved auditory function. These findings show that virus-induced cochlear inflammation during early auditory development, rather than direct virus-mediated damage, could contribute to histopathology in the cochlea and altered auditory function without significant loss of HCs in the sensory epithelium.

Authors

Cathy Yea Won Sung, Maria C. Seleme, Shelby Payne, Stipan Jonjic, Keiko Hirose, William Britt

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Figure 2

MCMV infection of newborn mice results in moderate to severe hearing loss.

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MCMV infection of newborn mice results in moderate to severe hearing los...
(A–C) ABR thresholds determined at P32 in noninfected control mice and mice infected as newborns with 200 or 500 PFU of MCMV. (A) Broadband clicks were presented to the animals in the following groups: noninfected, n = 18 mice/36 ears; 200 PFU MCMV n = 27 mice/54 ears; 500 PFU MCMV n = 24 mice/48 ears. P values calculated with 1-way ANOVA (Kruskal-Wallis test) with Dunn’s comparisons test. (B) Frequency-dependent tone-pips were used to determine the ABR thresholds in control and infected mice. Data shown as mean ± SD; noninfected control mice (blue solid line), n = 12 mice/24 ears; 200 PFU (red dashed line) MCMV, n = 27 mice/54 ears; and 500 PFU (red solid line) MCMV, n = 12 mice/24 ears. (C) For DPOAE testing, noninfected control mice (blue solid line), n = 8 mice/16 ears, and infected mice with elevated ABR click thresholds above 60 dB (red solid line), n = 7/14 ears were used. P values for frequency tone-pip and DPOAE were determined by 2-tailed unpaired t test (Mann-Whitney U test). (D) Sample ABR tracings from noninfected, control mouse (black) and MCMV-infected mouse (red) with ABR threshold of 25 dB and 75 dB, respectively, measured with broadband clicks. Note designation of wave I in control tracing with amplitude expressed in µV and latency in msec. *P < 0.05; **P < 0.01; ****P < 0.0001.