Murine CMV-induced hearing loss is associated with inner ear inflammation and loss of spiral ganglia neurons.
Murine CMV-induced hearing loss is associated with inner ear inflammation and loss of spiral ganglia neurons.
复制标题
鼠CMV引起的听力损失与内耳炎症和螺旋神经神经元的丧失有关。
DOI：
10.1371/journal.ppat.1004774
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发表时间：
2015-04
期刊：
影响因子：
6.7
通讯作者：
Britt WJ
中科院分区：
文献类型：
--
作者：
Bradford RD;Yoo YG;Golemac M;Pugel EP;Jonjic S;Britt WJ
先天性人巨细胞病毒（HCMV）发生在0.5-1%的活产婴儿中，约10%的感染婴儿会出现听力损失。听力损失的机制仍不清楚。我们开发了一种CMV诱导的听力损失的小鼠模型，其中新生小鼠的鼠巨细胞病毒（MCMV）感染导致病毒向内耳的血源性传播，诱导炎症反应和听力损失。在该模型中观察到先天性HCMV感染婴儿中描述的听力损失特征，包括延迟发作、进行性听力损失和单侧听力损失，并且这些特征是病毒接种物依赖性的。内耳中存在病毒抗原，螺旋神经节和血管纹中也存在CD 3+单核细胞。感染后螺旋神经节神经元密度降低，从而提供了听力损失的机制。听力损失小鼠的耳蜗中缺乏显著的内耳组织病理学和持续的炎症，提出了炎症是MCMV感染小鼠听力损失机制的主要组成部分的可能性。先天性人巨细胞病毒（HCMV）感染是胎儿最常见的病毒感染，在世界上大多数地区占所有活产婴儿的0.5-2.0%。胎儿感染可导致一系列终末器官疾病，包括中枢神经系统（CNS）的长期损伤。虽然不到10%的感染婴儿表现出终末器官疾病的临床证据，但高达10%的感染婴儿会出现听力损失。由于病理标本的可获得性和内耳的可获得性有限，导致听力损失的疾病机制知之甚少。现有的小动物模型未能概括这种内耳感染的许多特征。在这份报告中，我们描述了一个小鼠模型，其中新生动物外周感染鼠CMV发展听力损失后，血源性传播的病毒到内耳。听力损失发生在30-50%的动物中，先天性HCMV感染的婴儿的听力损失特征，包括迟发性听力损失、进行性听力损失和单侧听力损失，都存在于感染的小鼠中。我们的研究结果表明，宿主源性炎症反应，而不是直接的病毒介导的细胞病理学是听力损失的原因。这项研究的结果提供了深入了解先天性HCMV感染婴儿听力损失的潜在机制。
Congenital human cytomegalovirus (HCMV) occurs in 0.5–1% of live births and approximately 10% of infected infants develop hearing loss. The mechanism(s) of hearing loss remain unknown. We developed a murine model of CMV induced hearing loss in which murine cytomegalovirus (MCMV) infection of newborn mice leads to hematogenous spread of virus to the inner ear, induction of inflammatory responses, and hearing loss. Characteristics of the hearing loss described in infants with congenital HCMV infection were observed including, delayed onset, progressive hearing loss, and unilateral hearing loss in this model and, these characteristics were viral inoculum dependent. Viral antigens were present in the inner ear as were CD3+ mononuclear cells in the spiral ganglion and stria vascularis. Spiral ganglion neuron density was decreased after infection, thus providing a mechanism for hearing loss. The lack of significant inner ear histopathology and persistence of inflammation in cochlea of mice with hearing loss raised the possibility that inflammation was a major component of the mechanism(s) of hearing loss in MCMV infected mice. Congenital infection with human cytomegalovirus (HCMV) is the most common viral infection of the fetus and occurs in 0.5–2.0% of all live births in most regions in the world. Infection of the fetus can result in a spectrum of end-organ disease, including long term damage to the central nervous system (CNS). Although less than 10% of infected infants exhibit clinical evidence of end-organ disease, up to 10% of the total number of infected infants develop hearing loss. Mechanisms of disease leading to hearing loss are poorly understood because of the limited availability of pathological specimens and accessibility of the inner ear. Existing small animal models fail to recapitulate many features of this infection of the inner ear. In this report we describe a mouse model in which newborn animals infected peripherally with murine CMV develop hearing loss following hematogenous spread of virus to the inner ear. Hearing loss occurs in 30–50% of animals and characteristics of hearing loss in infants with congenital HCMV infection, including delayed onset of hearing loss, progressive hearing loss, and unilateral hearing loss were present in infected mice. Our findings suggest that host derived inflammatory responses and not direct virus-mediated cytopathology are responsible for hearing loss. Findings from this study provide insight into potential mechanisms of hearing loss in infants with congenital HCMV infection.
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传入剥夺引起了小鼠耳蜗核中关键时期后与神经元存活相关的转录反应。
影响因子：
5.3
作者：
Harris, Julie A.;Iguchi, Fukuichiro;Seidl, Armin H.;Lurie, Diana I.;Rubel, Edwin W.
通讯作者：
Rubel, Edwin W.
DOI：
10.1007/978-1-62703-788-4_17
发表时间：
2014-01-01
期刊：
HUMAN CYTOMEGALOVIRUSES: METHODS AND PROTOCOLS
影响因子：
--
作者：
Boppana, Suresh B.;Britt, William J.
通讯作者：
Britt, William J.
影响因子：
5.1
作者：
Fowler, KB;McCollister, FP;Pass, RF
通讯作者：
Pass, RF
影响因子：
2.5
作者：
Leake, Patricia A.;Hradek, Gary T.;Hetherington, Alexander M.;Stakhovskaya, Olga
通讯作者：
Stakhovskaya, Olga
影响因子：
4.8
作者：
Juanjuan C;Yan F;Li C;Haizhi L;Ling W;Xinrong W;Juan X;Tao L;Zongzhi Y;Suhua C
通讯作者：
Suhua C