Smith Matthew D, Seleme Maria C, Marquez-Lago Tatiana, Chen Jiung-Wen, Mach Michael, Britt William J
Department of Microbiology, Heersink School of Medicince, UAB, Birmingham, Ala, USA.
The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
J Neuroinflammation. 2025 Mar 23;22(1):92. doi: 10.1186/s12974-025-03416-4.
Human cytomegalovirus (HCMV) is the most common viral infection acquired in utero and a leading cause of neurodevelopmental abnormalities, including sensorineural hearing loss (SNHL). In previous studies using a murine model of HCMV induced SNHL, hearing loss was correlated with virus-induced cochlear inflammation but not cochlear viral load. However, these previous findings were determined at the time of auditory testing, a time poiont well past critical periods of auditory development. In the current study, cochlear virus load early in auditory development could be correlated with the magnitude of virus-induced cochlear inflammation, cochlear histopathology and the development of hearing loss. Transcriptional profiling at early times after infection revealed dysregulation of multiple well described deafness-related genes (DRG). Treatment with antiviral antibodies early after infection decreased cochlear virus load, cochlear inflammation, cochlear histopathology, and normalized DRG expression arguing that virus-induced cochlear inflammation can result in pleiotropic effects on the developing auditory system. Finally, this model also demonstrated that sterilizing immunity was unnecessary for prevention of SNHL, thus providing a rationale for inteventions that could limit, but not completely prevent HCMV infection of the developing auditory system.
人巨细胞病毒（HCMV）是最常见的先天性病毒感染，也是神经发育异常（包括感音神经性听力损失（SNHL））的主要原因。在先前使用HCMV诱导的SNHL小鼠模型的研究中，听力损失与病毒诱导的耳蜗炎症相关，但与耳蜗病毒载量无关。然而，这些先前的发现是在听觉测试时确定的，这是一个远远超过听觉发育关键期的时间点。在当前的研究中，听觉发育早期的耳蜗病毒载量可能与病毒诱导的耳蜗炎症程度、耳蜗组织病理学以及听力损失的发展相关。感染后早期的转录谱分析揭示了多个已充分描述的耳聋相关基因（DRG）的失调。感染后早期用抗病毒抗体治疗可降低耳蜗病毒载量、耳蜗炎症、耳蜗组织病理学，并使DRG表达正常化，这表明病毒诱导的耳蜗炎症可对发育中的听觉系统产生多效性影响。最后，该模型还表明，无菌免疫对于预防SNHL并非必要，从而为可能限制但不能完全预防发育中的听觉系统感染HCMV的干预措施提供了理论依据。
