| Project/Area Number |
13557014
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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 | 展開研究 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KIDO Hiroshi The University of Tokushima, Institute for Enzyme research, Professor, 分子酵素学研究センター, 教授 (50144978)
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| Co-Investigator(Kenkyū-buntansha) |
TASHIRO Masato The University of Tokushima, Head of Department of Vaccine, National Institute of Infectious Diseases, 部長(研究職) (90111343)
YAMADA Hiroshi The University of Tokushima, Institute for Enzyme research, Assistant Professor, 分子酵素学研究センター, 助手 (30343304)
OKUMURA Yuushi The University of Tokushima, Institute for Enzyme research, Assistant Professor, 分子酵素学研究センター, 助手 (70294725)
OUCHI Masato Kawasaki Medical School, Professor, 部生物学, 教授 (80107185)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2001: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Keywords | Influenza virus / Protease / triggering protease for infection / influenza associated / pneumonia / mini-plasmin encephalopathy / blood-brain barrier / edema / 血管-脳関門 / 脂肪酸代謝障害 / プラスミン / センダイウイルス / トリプシン / プロテアーゼ活性化レセプター / 血管-脳血管関門 / ウイルス増殖 |
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| Research Abstract |
Influenza virus infection including pandemic avian influenza virus in 2003 is one of the mast common infectious pathogens in humans and causes considerable morbidity and mortality. Recently inhibitors of influenza virus neuraminidase have been developed as anti-influenza drugs, which inhibit virus release from the cells at the budding stage. On the other hand, we have developed the inhibitar of virus envelope protein processing protease, which inhibit virus entry into the cells. In the term of this research project, we found four different bast cellular influenza virus envelope glycoprotein processing proteases, such as mini-plasmin, ectopic anionic trypsin, TMPRSS7 and TC30, other than tryptase Clara. These proteases distributed different locations in the airway and revealed different susceptibility for the virus envelope glycoprotein of various subtypes. Among them, expression of ectopic anionic trypsin increased in the lungs alter virus infection and may play a role in progression of virus spread and pneumonia. Mini-plasmin levels also increased at the inflammatory loci in the lungs after virus infection and accumulated on the cerebral capillaries through blood f low in mice having an impaired mitochondrial β-oxidation. In addition, accumulated mini-plasnmin destructed blood-brain barrier, resulting in brain edema and multiplication of the influenza virus in the brain capillaries. These findings implicate that disorder of mitochondrial β-oxidation and accumulation of mini-plasmin in the brain capillaries are the principal pathogens of influenza associated encephalopathy and Rye s syndrome. Based on these results, inhibitors of these virus envelope glycoprotein processing proteases may be important candidates for novel anti-influenza drugs. we are trying to find inhibitors of these processing proteases as anti-influenza drugs
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