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STUDY ON INFECTIOUS ROUTE OF HERPES SIMPLEX VIRUS FROM MUCOSA TO NERVOUS TISSUES

单纯疱疹病毒粘膜至神经组织的感染途径研究

基本信息

批准号：
14570265
负责人：
IWASAKI Takuya
金额：
$ 2.24万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

Herpes simplex virus (HSV) initially infects the, squamous cell epithelium of mucosa and skin, then, invade the peripheral nervous fibers in the subepithelial tissues at primary infection. Thereafter, HSV ascends through the nerve fibers to the soma of neurons in the central nervous system (CNS). In CNS HSV becomes to fall in a latent condition by host immune response. In this study we focused on the route of HSV infection from the squamous cell epithelium to the nervous fibers, in comparison with that of poliovirus because of similar usage of virus receptors.Various strains of HSV-2 including US2-deleted and its revertant recombinants, were inoculated on the corneal and vaginal surface of BALB/c mice. These mice were examined for their manifestations and histopathological changes. In addition, the. expression of immediate early protein (US1) was also investigated with respect to epithelial, subepithelial and nervous stages of viral infection and host immune responses.By immunohistochemical detection of US1 expression in formalin-fixed paraffin sections of HSV-2 inoculated mice, we have succeeded to orient the early infected cells, in which US1 antigen was detected in their nuclei. From this analysis we could demonstrate HSV-2 infection, in Schwann cells and satellite cells around the ganglion cells. In addition, the infection in Schwann cells without marked cellular destruction in the posterior column in the white matter of spinal cord is important to consider the pathogenesis of HSV-2 meningitis. Further study, we can reveal the difference of HSV-1 and HSV-2 after mucosal infection.

单纯疱疹病毒（HSV）最初感染粘膜和皮肤的鳞状细胞上皮，然后在原发性感染时侵入上皮下组织的周围神经纤维。此后，HSV通过神经纤维上升到中枢神经系统（CNS）的神经元体。在中枢神经系统中，HSV通过宿主免疫反应进入潜伏状态。在这项研究中，我们重点研究了HSV从鳞状细胞上皮到神经纤维的感染途径，与脊髓灰质炎病毒的感染途径相比，因为病毒受体的使用相似。将多种HSV-2毒株（包括us2缺失毒株及其相关重组毒株）接种于BALB/c小鼠角膜和阴道表面。观察小鼠的表现和组织病理变化。此外，。立即早期蛋白（US1）的表达也与病毒感染的上皮、上皮下和神经阶段以及宿主免疫反应有关。通过免疫组化检测US1在接种HSV-2小鼠的福尔马林固定石蜡切片中的表达，我们成功地定位了早期感染细胞，其中US1抗原在其细胞核中检测到。从这个分析中，我们可以证明HSV-2感染，在神经节细胞周围的雪旺细胞和卫星细胞中。此外，脊髓白质后柱未见明显细胞破坏的雪旺细胞感染是考虑2型单纯疱疹病毒脑膜炎发病机制的重要因素。进一步研究，我们可以揭示HSV-1和HSV-2在粘膜感染后的差异。