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Molecular mechanism of the infection and propagation of measles virus that cause subacute sclerosing panencephalitis

麻疹病毒感染和传播引起亚急性硬化性全脑炎的分子机制

基本信息

批准号：
17591108
负责人：
AYATA Minoru
金额：
$ 2.18万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591108/
关键词：
measles virus subacute sclerosing panencephalitis reverse genetics neurovirulence

项目摘要

Measles virus (MV) isolated from a brain of a patient with subacute sclerosing panencephalitis (SSPE) can cause acute encephalopathy in hamster when it was inoculated intracerebrally. Here we studied the molecular mechanism of the infection and propagation of MV that caused SSPE. Plasmids were constructed from the plasmid that contained full-length genome of the wild-type MV IC-B strain by substituting the genes from MV SSPE strain Osaka-1 or Osaka-2. Six recombinant viruses that contained either of F or H, or both of them prepared from the two SSPE strains, were rescued. These recombinant viruses were infected into various cell lines and their cell tropism and cytopathological effects were compared. Similar to the original MV SSPE strains, these recombinant viruses were considerably defective in cell-free virus production. In addition, recombinant viruses that contained the SSPE F gene infected IMR-32 neuroblastoma cells as well as Vero cells and formed syncytia. This implicated the augmentation of the fusogenic activity of the F protein that was triggered by the specific interaction of the H protein with an unidentified receptor. Furthermore, these SSPE F gene-containing viruses caused a lethal encephalopathy in hamsters. Recombinant viruses that contained the SSPE H gene also showed some neuropathogenicity but most hamsters survived. In contrast, recombinant viruses that contained the SSPE M gene did not show any neurological signs in hamsters. These studies indicated the importance of the structural alteration of the F and H protein for the propagation of MV in the brain and the pathogenesis of SSPE.

从亚急性硬化性全脑炎（SSPE）患者脑内分离的麻疹病毒（MV）经脑内接种可引起地鼠急性脑病。本研究从分子水平探讨了MV侵染和增殖引起SSPE的分子机制。通过替换来自MV SSPE株Osaka-1或Osaka-2的基因，从含有野生型MV IC-B株的全长基因组的质粒构建质粒。从两株SSPE中分别获得6株含有F或H或两者的重组病毒。将这些重组病毒感染不同的细胞系，比较它们的细胞嗜性和细胞病理学效应。与原始MV SSPE株系相似，这些重组病毒在无细胞病毒生产方面存在相当大的缺陷。此外，含有SSPE F基因的重组病毒感染IMR-32神经母细胞瘤细胞以及Vero细胞并形成合胞体。这暗示了F蛋白的融合活性的增强，其由H蛋白与未鉴定的受体的特异性相互作用触发。此外，这些含有SSPE F基因的病毒在仓鼠中引起致死性脑病。含有SSPE H基因的重组病毒也显示出一定的神经致病性，但大多数仓鼠存活。相反，含有SSPE M基因的重组病毒在仓鼠中未显示任何神经学体征。这些研究表明F和H蛋白的结构改变对于MV在脑中的传播和SSPE的发病机制的重要性。