Department of Microbiology and.
Department of Pediatrics, University of Alabama School of Medicine, Birmingham, Alabama, USA.
JCI Insight. 2019 Sep 5;4(17):128878. doi: 10.1172/jci.insight.128878.
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.
虽然人类巨细胞病毒（HCMV）是导致先天性 HCMV（cCMV）感染婴儿感音神经性听力损失的已知原因，但导致 cCMV 感染婴儿感音神经性听力损失（SNHL）的机制尚不清楚。在听觉发育过程中使用 CMV 感染的小鼠模型，我们已经表明，新生小鼠的外周感染鼠巨细胞病毒（MCMV）会导致耳蜗的局灶性感染和病毒诱导的耳蜗炎症。大约 50%-60%的感染小鼠表现出一系列声音频率的听觉脑干反应（ABR）阈值升高。对 ABR 阈值升高的 MCMV 感染小鼠的耳蜗进行组织学分析显示，毛细胞（HC）数量和形态在 Corti 器官中得以保留。相比之下，螺旋神经节神经元（SGN）、突触和连接耳蜗 HC 和 SGN 神经末梢的神经纤维的数量减少。通过对 MCMV 感染小鼠进行皮质类固醇治疗以减少耳蜗炎症，可保留 SGN 并改善听觉功能。这些发现表明，早期听觉发育过程中病毒诱导的耳蜗炎症，而不是直接的病毒介导的损伤，可能导致耳蜗的组织病理学改变和听觉功能改变，而感觉上皮中的 HC 没有明显丢失。
