Restricted infection of murine cytomegalovirus (MCMV) in neonatal mice with MCMV-induced sensorineural hearing loss

Restricted infection of murine cytomegalovirus (MCMV) in neonatal mice with MCMV-induced sensorineural hearing loss
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DOI:
10.1016/j.jcv.2015.06.083
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发表时间:
2015-08-01
影响因子:
8.8
通讯作者:
Suzutani, Tatsuo
Suzutani, Tatsuo
中科院分区:
医学3区
文献类型:
--
作者:
Ikuta, Kazufumi;Ogawa, Hiroshi;Suzutani, Tatsuo

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背景:人类巨细胞病毒(HCMV)先天性感染是感音神经性耳聋(SNHL)的病因之一。目的:通过对耳蜗人巨细胞病毒(CMV)感染部位的鉴定,阐明SNHL的非遗传病因。研究设计:新生Balb/c小鼠出生后24 h内注射小鼠脑内巨细胞病毒(MCMV)建立SNHL动物模型。结果:出生后3周,单侧和双侧SNHL发生率分别为24%(5/21)和29%(6/21)。此后SNHL进展,79%的小鼠在6周龄时发展为双侧SNHL。1周龄时在螺旋神经节、脑膜周围和鼓阶周围的细胞中检测到MCMV抗原和DNA。然而,MCMV抗原和DNA在2周龄时完全消失。MCMV可能是脑膜炎通过脑脊液到达螺旋神经节的结果,因为血管纹MCMV抗原为阴性。肌球蛋白VI在外毛细胞中的表达在3周龄时消失。结论:从MCMV抗原/DNA阳性细胞到SNHL发生和肌球蛋白VI阴性毛细胞之间存在一定的滞后时间。MCMV在外毛细胞肌球蛋白VI表达缺失中的作用有待进一步研究。(C)2015爱思唯尔B.V.保留所有权利。
Background: Congenital infection with human Cytomegalovirus (HCMV) is known to be a causative agent of sensorineural hearing loss (SNHL).Objectives: To clarify the nongenetic etiology of SNHL by identifying the Cytomegalovirus (CMV)-infected region in the cochleae.Study design: We established an animal model of SNHL by injecting neonatal Balb/c mice with intracerebral murine Cytomegalovirus (MCMV) within 24 h after delivery.Results: At 3 weeks of age, unilateral and bilateral SNHL were observed in 24% (5/21) and 29% (6/21) of the mice, respectively. SNHL thereafter progressed, with 79% of mice developing bilateral SNHL by 6 weeks of age. MCMV antigens and DNA were detected in the spiral ganglion, and cells surrounding the meninges and scala tympani at 1 week of age. However, both MCMV antigens and DNA had completely disappeared by 2 weeks of age. It is possible that the MCMV reached the spiral ganglion via cerebrospinal fluid as the result of meningitis, as the stria vascularis was found to be MCMV antigen negative. Myosin VI expression in the outer hair cells was lost at 3 weeks of age. MCMV and myosin VI expression disappeared before and during SNHL progression, respectively.Conclusions: There was a definite lag time between the period in which MCMV antigens/DNA-positive cells were observed and that in which SNHL developed and myosin VI-negative hair cells were observed. Further study is needed to explore the role of MCMV in the loss of myosin VI expression in the outer hair cells. (C) 2015 Elsevier B.V. All rights reserved.