2011 Fiscal Year Final Research Report
Development of new therapeutics for a highly pathogenic influenza virus infection by inhibition of virus entry and multiplication
| Project/Area Number |
21249061
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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 |
Infectious disease medicine
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KIDO Hiroshi 徳島大学, 疾患酵素学研究センター, 教授 (50144978)
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| Co-Investigator(Renkei-kenkyūsha) |
CHIDA Junji 徳島大学, 疾患酵素学研究センター, 助教 (20437651)
YOUSSOUF Cisse 徳島大学, 疾患酵素学研究センター, 研究員 (80437649)
MIZUNO Dai 徳島大学, 疾患酵素学研究センター, 助教 (70380061)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 高病原性鳥インフルエンザ / プロセシングプロテアーゼ / 多臓器不全 / サイトカインストーム / トリプシン / MMP-9 / ミトコンドリア膜電位 / ATP産生 |
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| Research Abstract |
We found that type II membrane bound serine proteases MSPL/ TMPRSS13 are essential cellular factors for entry into cells of the highly pathogenic avian influenza(HPAI) viruses. To confirm the evidence, we have made TPMRSS13 KO mice and challenged the viruses to the animals. Viral multiplication of the HPAI viruses with the hemagglutinin(HA) cleavage site sequence RKKR partially and the sequence KKKR was completely suppressed in the TPMRSS13 KO mice. The results indicate that MSPL/ TMPRSS13 are essential for the entry of the HPAI virus. Furthermore, we found that viral infection stimulates the influenza. cytokine. protease cycle and the cycle plays an important role in the pathogenicity of multiple organ failure induced by infection.
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