| Project/Area Number |
10680785
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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 |
Laboratory animal science
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| Research Institution | Osaka Prefectural Institute of Public Health |
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Principal Investigator |
ITOH Masae Osaka Prefectural Institute of Public Health, Virology Division, Senior Researcher, 公衆衛生部, 主任研究員 (10201328)
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| Co-Investigator(Kenkyū-buntansha) |
HOTTA Hak Kobe University School of Medicine, Department of Microbiology, Professor, 医学部, 教授 (40116249)
中川 直子 大阪府立公衆衛生研究所, 公衆衛生部, 主任研究員 (10280835)
OKUNO Yoshinobu Osaka Prefectural Institute of Public Health, Virology Division, Director, 公衆衛生部, ウイルス課長 (30112064)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Sendai virus / pathogenicity / apoptosis / necrosis / interferon |
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| Research Abstract |
(1) Identification of Sendai virus genes which determine mouse pathogenicity.
Comparing an attenuated mutant virus (MVC11) with a highly pathogenic wild-type virus (M1), we showed the single point mutation from Phe to Ser at the 170th position of the C protein abolished the virulence of Sendai virus against mice. Involvement of the C protein in pathogenicity was confirmed by examining some recombinant viruses recovered by means of reverse genetics which were lacking one or two of the set of the C proteins (C', C, Y1 and Y2).
(2) Mechanism of attention of the c protein mutant.
1) Interferon sensitivity: When MVC11 was infected to interferon α/β receptor (IFNR)-knock-out mice (A129), mice exhibited only slight decrease of body weight. The result demonstrated that MVC11 was attenuated in A129 to the same degree as in ordinary mice possessing IFNR, suggesting that interferon sensitivity does not relate to attenuation of MVC11.
2) Effect of death of infected cells: Attenuated viruses with mutations in the C protein like MVC11 induced necrosis as well as apoptosis. Death of the infected cells caused interruption of progeny virus production afterwards, and resulted in attenuation of viral pathogenicity. On the other hand, pathogenic viruses like M1 did not demonstrate significant cytopathic effect and released progeny virus continuously for a long time after infection. In the presence of caspase inhibitor which suppressed apoptosis but not necrosis, MVC11-infected cells died rapidly. These results suggested that necrosis plays an important role in causing death to attenuated virus-infected cells.
(3) Growth of recombinant Sendai virus: Recombinant virus of Sendai virus obtained from cDNA of the attenuated laboratory strain (Z), the C gene of which was substituted by that of MVC11 did not grow efficiently. Based on this observation, we are trying to introduce mutations into the F and V genes of MVC11 with the aim to establish multiply attenuated virus.
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