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 1

I.p. inoculation of newborn mice with MCMV results in cochlear infection and inflammation.

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I.p. inoculation of newborn mice with MCMV results in cochlear infection...
(A) MCMV DNA was extracted from the cochlea and quantified as described in Methods, with each data point representing genome copy number in single cochlea. (B) Representative images of cochleae from noninfected, control (top) and MCMV-infected (bottom) mice displaying inflammatory response. Midmodiolar cochlear sections of P8 MCMV-infected mice were immunostained for MCMV IE-1 protein (green) and Iba-1 (red), a marker for activated myeloid cells, and nuclear stain (blue) (10× magnification). A higher-magnification of area of interest (boxed area) in cochlea from MCMV-infected mouse is shown on the right (40× magnification). A total of n = 3 mice/n = 6 cochleae were stained. Scale bars: 100 μm. (C) Expression of interferon-stimulating gene (ISG), IFIT1, and (D) proinflammatory cytokine TNF-α were measured by reverse transcription PCR at various time points from RNA extracted from cochlea as described in Methods. HPRT was used as internal control, and fold change was normalized to the noninfected, control cochlea. For each time point, n = 4–6 mice were assayed.