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

从亚急性硬化性全脑炎(SSPE)患者脑内分离到的麻疹病毒(MV)经脑内接种可引起金黄地鼠急性脑病。在此，我们研究了引起SSPE的MV侵染和繁殖的分子机制。以野生型MVIC-B株的全长基因组为模板，替换MVSSPE株Osaka-1或Osaka-2的基因，构建了含野生型MVIC-B株全长基因组的质粒。从两个SSPE菌株制备的F或H或同时含有F或H的6个重组病毒被拯救。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株相似，这些重组病毒在生产无细胞病毒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神经母细胞瘤细胞和Vero细胞并形成合胞体。这暗示了由H蛋白与未知受体的特定相互作用所触发的F蛋白融合活性的增强。此外，这些含有SSPE F基因的病毒会引起仓鼠的致死性脑病。含有SSPE H基因的重组病毒也显示出一定的神经致病性，但大多数仓鼠都存活了下来。相比之下，含有SSPE M基因的重组病毒在仓鼠身上没有表现出任何神经症状。这些研究表明，F和H蛋白的结构变化在MV在脑内的传播和SSPE的发病机制中具有重要意义。

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.