2006 Fiscal Year Final Research Report Summary
Molecular mechanism of the infection and propagation of measles virus that cause subacute sclerosing panencephalitis
| Project/Area Number |
17591108
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Osaka City University |
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Principal Investigator |
AYATA Minoru Osaka City University, Graduate School of Medicine, Research Associate, 大学院医学研究科, 助手 (90222702)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Hiroshi Osaka City University, Graduate School of Medicine, Registered Doctor, 登録医 (50382081)
OHGIMOTO Shinji Osaka City University, Graduate School of Medicine, Lecturer, 講師 (80292853)
OGURA Hisashi Osaka City University, Graduate School of Medicine, Professor, 教授 (10115222)
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| Project Period (FY) |
2005 – 2006
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| Keywords | measles virus / subacute sclerosing panencephalitis / reverse genetics / neurovirulence |
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| Research Abstract |
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.
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