Inflammation and Hearing Loss Following Congenital CMV Infection

摘要： 与先天性人类巨细胞病毒(HCMV)感染相关的听力损失 频繁的围产期感染，占婴儿听力损失所有原因的近25%， 美国的儿童。由此引起内耳感染的致病机制 大型疱疹病毒是未知的，主要是因为在对 人类的内耳。我们已经开发了一种有信息的小鼠听力损失模型，在这种模型中 新生的小鼠是外周感染的，而不是体内感染的 CMV.在这个模型中，大约30%-50%的感染小鼠发展为感觉神经性听力损失和一种 大量患有听力损失的小鼠表现出听力损失的进展，临床上 婴儿巨细胞病毒相关性听力损失的重要特征。我们的发现 强烈认为是病毒引起的炎症，而不是直接的病毒细胞病理学 在该模型中用于听力损失和进行性听力损失。我们的研究将探索这一点 通过定义对发育中的听觉系统和听力的损害机制来提出假说 与巨细胞病毒引起的内耳炎症有关的动物损失。来自这些的结果 研究将指导对婴儿和儿童听力损失机制的调查 与巨细胞病毒相关的听力损失，并确定可转化为 巨细胞病毒感染婴幼儿听力损失的治疗与预防

Abstract: Hearing loss associated with congenital human cytomegalovirus (HCMV) infection, a relatively frequent perinatal infection, accounts for nearly 25% of all causes of hearing loss in infants and children in the US. The mechanisms of disease caused by infection of the inner ear by this large herpesvirus are unknown, primarily because of hurdles inherent in the investigation of the inner ear in humans. We have developed an informative murine model of hearing loss in which newborn mice are infected peripherally and not intracranially with the closely related murine CMV. In this model, about 30-50% of infected mice develop sensorineural hearing loss and a significant number of mice with hearing loss exhibit progression in hearing loss, a clinically important feature of hearing loss in infants with HCMV associated hearing loss. Our findings strongly argue that virus-induced inflammation and not direct viral cytopathology is responsible for hearing loss and progressive hearing loss in this model. Our studies will explore this hypothesis by defining mechanisms of damage to the developing auditory system and hearing loss in animals associated with CMV-induced inflammation of the inner ear. Results from these studies will guide investigation into mechanisms of hearing loss in infants and children with HCMV associated hearing loss and identify therapeutic approaches that can be translated into treatment and prevention of hearing loss in CMV infected infants.