2000 Fiscal Year Final Research Report Summary
Viral factors responsible for the neurovirulence of SSPE virus
| Project/Area Number |
10670290
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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 |
Virology
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| Research Institution | Osaka City University |
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Principal Investigator |
AYATA Minoru Medical School, Osaka City University Research Associate, 医学部, 助手 (90222702)
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| Co-Investigator(Kenkyū-buntansha) |
KOMASE Katsuhiro Kitasato Institute, Research Center for Biologicals Division of Research and Development, Division leader, 生物製剤研究所・開発研究部門, 部門長(研究職) (80215384)
OGURA Hisashi Medical School, Osaka City University Professor, 医学部, 教授 (10115222)
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| Project Period (FY) |
1998 – 2000
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| Keywords | subacute sclerosing panencephalitis / SSPE vius / nucleotide sequence / mutation / transcription |
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| Research Abstract |
To Identify viral factors responsible for the neurovirulence of subacute sclerosing panencephalitis(SSPE) virus, we have determined nucleotide sequences of the Osaka-1, -2, and -3 strains of SSPE virus. Comparison of the sequence of the P-M junction revealed a variation among SSPE viruses. The wild-type P gene end(3'-UUUUUU-5')was mutated to 3'-UUUUU-5' for the Osaka-1 strain by a single nucleotide deletion, or mutated to 3'-UUUCUU-5' for the OSA-2/Fr/B sibling virus of the Osaka-2 strain. To clarify the significance of these mutations for the transcriptional termination of the P gene, we have constructed dicistronic minigenomes which contained the Firefly and the Renilla luciferase genes, separated by insertion of different types of mutated P-M junction sequence between the two reporter genes. The luciferase assay demonstrated that these mutations were solely responsible for the read-through of mRNA synthesis. The F gene sequence analysis revealed that all the three SSPE viruses had significant mutations in the cytoplasmic domain of the F protein. The binding of the virus with the cellular receptor CD46 was determined by the hemadsorption assay of Vero cells transfected with the cloned H cDNAs. The results of the negative hemadsorption of cells transfected with H genes from SSPE strains revealed that the original property of the H protein of the progenitor measles virus was conserved during persistent infection. In addition, some specific amino acid substitutions were responsible for the interaction between the H protein and CD46. Co-expression experiments of the cloned F and H cDNAs from SSPE viruses reproduced the cytopathic effect similarly to the viral infection. Further functional studies of the mutations in the F and H protein will reveal the differences between SSPE and measles strains. These results will also provide a new insight into the receptor for SSPE viruses.
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[Publications] Seto, T., Ayata, M., Hayashi, K., Furukawa, K., Murata, R., Ogura, H.: "Different transcriptional expression of the matrix gene of the two sibling viruses of the subacute sclerosing panencephalitis virus(Osaka-2 strain)isolated from a biopsy specimen of patient brain."J.Neurovirol. 5(2). 151-160 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Furukawa, K., Ayata, M., Kimura, M., Seto, T., Matsunaga, I., Murata, R., Yamano, T., Ogura, H.: "Hemadsorption expressed by cloned H genes from subacute sclerosing panencephalitis(SSPE) viruses and their possible progenitor measles viruses isolated in Osaka, Japan."Microbiol.Immunol.. 45(1). 59-68 (2001)
Description
「研究成果報告書概要(欧文)」より
