| Project/Area Number |
11694210
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied veterinary science
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| Research Institution | Tottori University |
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Principal Investigator |
ITO Toshihiro Tottori University, Faculty of Agriculture, Professor, 農学部, 教授 (00176348)
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| Co-Investigator(Kenkyū-buntansha) |
KIDA Hiroshi Hokkaido University, Faculty of Veterinary Medicine, Professor, 獣医学部, 教授 (10109506)
ITO Hiroshi Tottori University, Faculty of Agriculture, Assistant Professor, 農学部, 講師 (10332777)
OTSUKI Koichi Tottori University, Faculty of Agriculture, Professor, 農学部, 教授 (00032293)
HORIMOTO Taisuke Tokyo University Medical Institute, Associate Professor, 医科学研究所, 助教授 (00222282)
河岡 義裕 東京大学, 医科学研究所, 教授
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥12,990,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥990,000)
Fiscal Year 2001: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2000: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | influenza virus / fowl plague / host range / pathogenicity / chicken / H5 / pandemic / recerse genetics / 新型ウイルス / ヘマグルチニン / 開裂 / レセプター |
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| Research Abstract |
An H5N1 avian influenza A virus was transmitted to humans in Hong Kong in 1997. Although the virus causes systemic infection and is highly lethal in chickens because of the susceptibility of the hemagglutinin to furin and PC6 proteases, their virulence in mice revealed two distinct groups of viruses : group 1, for which the dose lethal for 50 % of mice (MLD_<50>) was between 0.3 and 11 PFU, and group 2, for which the MLD_<50> was more than 10^3 PFU. The failure of some H5N1 viruses to produce systemic infection in our model indicates that multiple, factors contribute to the severity of H5N1 infection in mammals. In addition, our experimental passages of a waterfowl isolate through chickens demonstrated that avirulent viruses maintained in wild waterfowl in nature have the potential to become highly pathogenic while circulating in chickens. The series of virulence mutants isolated in the present study not only lend insight into mechanisms of virulence acquisition but may also provide a useful tool, in combination with reverse genetics, with which to generate influenza viruses from plasmids.
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