| Project/Area Number |
19390135
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | National Institute of Infectious Diseases |
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Principal Investigator |
TAGUCHI Fumihiro National Institute of Infectious Diseases, 獣医学部, 准教授 (30107429)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Rihito 日本獣医生命科学大学, 創価大工学部, 教授 (30129746)
SHIRATO Kazuya 国立感染症研究所, ウイルス第3部, 研究員 (40415477)
HIRAI Asuka 国立感染症研究所, ウイルス第3部, 研究員 (50450557)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2009: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2008: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2007: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | 病原性 / コロナウイルス / 豚下痢症ウイルス(PEDV) / 神経病原性 / 巨細胞形成 / ウイルス受容体 / マウス肝炎ウイルス / recetor-indeendent infection / ブタ伝染性下痢ウイルス(PEDV) / 乳飲みマウス / 脳内継代 / スパイク(S)蛋白 |
|---|
| Research Abstract |
Murine coronavirus wild type (wt) JHM strain infects in a receptor-independent fashion (receptor independent infection, RII in short), while a mutant isolated from wild type wt JHM, called srr7, lacks this activity, when examined at 24 hours after infection of mixed neural cell culture. However, variant viruses with RII activity were isolated from srr7 infected mixed cells, when infection was maintained for 3 days. Wt JHM with RII activity showed high neurovirulence for mice, killing those mice within 2-3 days after infection. Srr7 also killed mice when higher dose was inoculated after longer survival time compared with that of wt JHM. Wt JHM antigen was detected in a variety of neural cells, which may be attributed to the RII in mouse brain. However, srr7 antigen was not widely distributed. These results suggest the possibility that high virulence of JHM is attributed to the RII activity. We also tried to obtain porcine coronavirus that grows and shows the virulence for mice to see whether coronaviruses other than JHM display RII activity. After passage of Vero-cell adapted porcine epidemic diarrhea virus (PEDV) through suckling mouse brain, we obtained variant with higher virulence for mice, which shows enhanced cell-cell fusion activity compared with original, non-adapted virus. The mutant showed 4 amino acids mutation in the S protein which is believed to be critical for cell-cell fusion. However, it is not understood whether those mutations in the S could be responsible for higher virulence. In order to pursue this issue, we have to establish the reverse genetics system of PEDV
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