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著作: [木戸 博]/[奥村 裕司]/[高橋 悦久]/Pan HY/[Wang Siye]/[千田 淳司]/[Quang Le]/[矢野 仁康]/Host envelope glycoprotein processing proteases are indispensable for entry into human cells by seasonal and highly pathogenic avian influenza viruses./[Journal of Molecular and Genetic Medicine]

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EID
289509
EOID
870271
Map
0
LastModified
2017年8月28日(月) 20:16:12
Operator
大家 隆弘
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TRUE
Censor
0
Owner
高橋 悦久
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
審査 推奨
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著者 必須
  1. 木戸 博([徳島大学.先端酵素学研究所.重点研究部門])
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    学籍番号 推奨
  2. 奥村 裕司
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  3. 高橋 悦久([徳島大学.先端酵素学研究所.重点研究部門])
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    貢献度 任意
    学籍番号 推奨
  4. (英) Pan HY
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    学籍番号 推奨
  5. Wang Siye
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  6. 千田 淳司([徳島大学.先端酵素学研究所.基幹研究部門])
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  7. Quang Le
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  8. 矢野 仁康
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題名 必須

(英) Host envelope glycoprotein processing proteases are indispensable for entry into human cells by seasonal and highly pathogenic avian influenza viruses.

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(英) Influenza A virus (IAV) is one of the most common infectious pathogens in humans and causes considerable morbidity and mortality. The recent spread of highly-pathogenic avian IAV H5N1 viruses has reinforced the importance of pandemic preparedness. In the pathogenesis of IAV infection, cellular proteases play critical roles in the process of viral entry into cells that subsequently leads to tissue damage in the infected organs. Since there are no processing protease for the viral membrane fusion glycoprotein hemagglutinin precursor (HA(0)) in IAV, entry of the virus into cells is determined primarily by the host cellular HA(0) processing proteases that proteolytically activate membrane fusion activity. HA(0) of seasonal human IAV has the consensus cleavage site motif Q(E)-T/X-R and is selectively processed by at least seven different trypsin-type processing proteases identified to-date in animal model experiments using mouse-adapted IAV or gene expression system in MDCK cells. As is the case for the highly pathogenic avian influenza (HPAI) A virus, endoproteolytic processing of the HA(0) occurs through ubiquitous cellular processing proteases, which selectively recognize the multi-basic consensus cleavage site motifs, such as R-X-K/R-R, and K-X-K/R-R. The cleavage enzymes for the R-X-K/R-R motif, but not K-X-K/R-R motif, have been reported to be furin and pro-protein convertase (PC)5/6 in the trans-Golgi network. Here we report new members of type II transmembrane serine proteases of the cell membrane, mosaic serine protease large form (MSPL) and its splice variant TMPRSS13, which recognize and cleave both R-X-K/R-R and K-X-K/R-R motifs without calcium. Furthermore, IAV infection significantly up-regulates a latent ectopic pancreatic trypsin, one of the potent HA processing proteases, and pro-matrix metalloprotease-9, in various organs. These proteases may synergistically damage the blood-brain barrier in the brain and basement membrane of blood vessels in various organs, resulting in severe edema and multiple organ failure. In this review, we discuss these proteases as new drug target molecules for IAV treatment acting by inhibition of IAV multiplication and prevention of multiple organ failure, other than anti-viral agents, viral neuraminidase inhibitors.

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誌名 必須 Journal of Molecular and Genetic Medicine(Library Publishing Media)
(eISSN: 1747-0862)
ISSN 任意 1747-0862
ISSN: 1747-0862 (eISSN: 1747-0862)
Title: Journal of molecular and genetic medicine : an international journal of biomedical research
Title(ISO): J Mol Genet Med
Publisher: OMICS Publishing Group
 (NLM Catalog  (CrossRef (No Scopus information.)
必須 3
必須 1
必須 167 175
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年月日 必須 2009年 1月 初日
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PMID 任意 19565019    (→Scopusで検索)
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  1. (英) Article.PublicationTypeList.PublicationType: Journal Article

  2. (英) OtherID: PMC2702071

  3. (英) KeywordList.Keyword: Influenza virus

  4. (英) KeywordList.Keyword: TMPRSS-13

  5. (英) KeywordList.Keyword: hemagglutinin processing protease

  6. (英) KeywordList.Keyword: highly pathogenic avian influenza virus

  7. (英) KeywordList.Keyword: mini-plasmin

  8. (英) KeywordList.Keyword: trypsin

  9. (英) KeywordList.Keyword: tryptase Clara