Induction of cytomegalovirus-infected labyrinthitis in newborn mice by lipopolysaccharide: a model for hearing loss in congenital CMV infection
Induction of cytomegalovirus-infected labyrinthitis in newborn mice by lipopolysaccharide: a model for hearing loss in congenital CMV infection
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DOI：
10.1038/labinvest.2008.39
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发表时间：
2008-07-01
影响因子：
5
通讯作者：
Tsutsui, Yoshihiro
中科院分区：
文献类型：
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作者：
Li, Li;Kosugi, Isao;Tsutsui, Yoshihiro
先天性巨细胞病毒(CMV)感染是儿童感音神经性耳聋最常见的感染性原因。在这里，我们建立了新生小鼠全身感染小鼠巨细胞病毒(MCMV)后听力损失的实验模型。虽然在内耳和脑内几乎没有观察到病毒感染(Ip)。新生小鼠感染MCMV，这些区域的感染是与脑内(I.C.)注射细菌脂多糖(LPS)。就单位重量的病毒滴度而言，内耳的敏感度高于大脑。在迷路中，病毒感染与间充质血管相关，并伴有内毒素诱导的炎症细胞，在迷路内形成血源性感染靶点。病毒感染也在鼓阶和前庭阶外淋巴区域传播，可能是通过脑膜源性和耳蜗神经途径从受感染的大脑传播。在包括Corti器官在内的内淋巴中，未观察到病毒感染。然而，在螺旋状角膜缘，包括血管纹，观察到病毒感染。这些结果提示，先天性巨细胞病毒感染后迷路炎所致的听力损失可能是由于新生儿期全身细菌感染引起的炎症所致。
Congenital cytomegalovirus (CMV) infection is the most common infectious cause of sensorineural hearing loss in children. Here, we established an experimental model of hearing loss after systemic infection with murine CMV (MCMV) in newborn mice. Although almost no viral infection was observed in the inner ears and brains by intraperitoneal (i.p.) infection with MCMV in newborn mice, infection in these regions was induced in combination with intracerebral (i.c.) injection of bacterial lipopolysaccharide (LPS). The susceptibility of the inner ears was higher than that of the brains in terms of viral titer per unit weight. In the labyrinths, the viral infection was associated with the mesenchymal vessels and accompanied by inflammatory cells induced by LPS, causing hematogenous targets of infection in the labyrinths. Viral infection also spread in the perilymph regions such as the scala tympani and scala vestibuli, probably from infected brains via meningogenic and cochlear nerve routes. Viral infection was not observed in the scala media in the endolymph, including the Corti organ. However, viral infection was observed in the spiral limbus, including the stria vascularis. These results suggest that hearing loss caused by labyrinthitis after congenital CMV infection may be enhanced by inflammation caused by systemic bacterial infection in the neonatal period.