Discovery of the potentiating proteases for influenza virus infection and their inhibitors as defensive compounds
发现流感病毒感染的增强蛋白酶及其作为防御化合物的抑制剂
基本信息
- 批准号:10557033
- 负责人:
- 金额:$ 8.26万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B).
- 财政年份:1998
- 资助国家:日本
- 起止时间:1998 至 2000
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Post-translational proteolytic cleavage of precursors of the envelope fusion glycoproteins of RNA viruses is indispensable for virus entry into host cells. It is widely known that the pathogenicity of mammalian and nonpathogenic avian influenza viruses, and Sendai virus is primarily determined by host cellular processing proteases in the respiratory tract, which proteolytically induce fusion of viral envelope glycoproteins, HA of influenza viruses, and F0 of Sendai virus with the plasma membrane of target cells, allowing the viral genome to enter the cytoplasm. In the period granted by this foundation, we found new members of protease in airway that, like tryptase Clara, can process influenza A virus hemagglutinin and Sendai virus envelope fusion glycoprotein. One was found in the epithelial cells of the upward divisions of bronchioles and identified to be a mini-plasmin. Mini-plasmin potentiated the replication of broad-spectrum influenza A viruses and Sendai virus, even that of the plasmin-insensitive influenza A virus strain. The other was found in the epithelial cells of alveolar of rat lungs and was identified to be an ectopic anionic pancreatic trypsin. Mucus protease inhibitor(MPI)in nasal liquids and bronchial lavage inhibited the activity of tryptase Clara and partly that of trypsin. Mini-plasmin was not inhibited by α1-antiplasmin and MPI.These findings indicate that there are several proteases potentiating the infectivity of influenza virus in different loci in airway and the infectivity of influenza virus is regulated by the balance between the amounts of these proteases and their inhibitors in airway.
RNA病毒包膜融合糖蛋白前体的翻译后蛋白水解切割是病毒进入宿主细胞所必需的。众所周知,哺乳动物和非致病性禽流感病毒以及仙台病毒的致病性主要由呼吸道中的宿主细胞加工蛋白酶决定,所述蛋白酶通过蛋白水解诱导病毒包膜糖蛋白、流感病毒的HA和仙台病毒的F0与靶细胞的质膜融合,从而允许病毒基因组进入细胞质。在该基金会的资助下,我们在气道中发现了新的蛋白酶成员,它们与类胰蛋白酶Clara一样,可以处理甲型流感病毒血凝素和仙台病毒包膜融合糖蛋白。一种在细支气管向上分支的上皮细胞中发现,并被鉴定为微型纤溶酶。微型纤溶酶可增强广谱甲型流感病毒和仙台病毒的复制,甚至增强对纤溶酶不敏感的甲型流感病毒株的复制。另一种存在于大鼠肺泡上皮细胞中,经鉴定为异位阴离子胰蛋白酶。鼻液和支气管灌洗液中的粘液蛋白酶抑制剂(MPI)抑制类胰蛋白酶Clara的活性,部分抑制胰蛋白酶的活性。α1-抗纤溶酶和MPI均不抑制微小纤溶酶,提示在气道不同部位存在多种增强流感病毒感染性的蛋白酶,流感病毒的感染性受这些蛋白酶及其抑制剂在气道中的平衡调节。
项目成果
期刊论文数量(100)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
木戸 博: "インフルエンザQ & A"永武毅(医薬ジャーナル社). 12 (2000)
Hiroshi Kido:“流感问答”Takeshi Nagatake(Iyaku Journal)12(2000)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
木戸 博: "ヒト粘液のプロテアーゼインヒビターによるインフルエンザウイルスの感染抑制"治療学. 38(2). 1005-1009 (1998)
Hiroshi Kido:“人类粘液蛋白酶抑制剂抑制流感病毒感染”38(2) (1998)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Ye Chen et al.: "Mast cell tryptase from pig lungs triggers infection by pneumotropic Sendai and influenza A viruses."Eur.J.Biochem.. 267(11). 3189-3197 (2000)
Ye Chen 等人:“猪肺肥大细胞类胰蛋白酶引发嗜肺仙台病毒和甲型流感病毒感染。”Eur.J.Biochem. 267(11)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Hiroshi Kido et al.: "Human mucus protease inhibitor and its mutants are novel defensive compounds against infection with influenza A and Sendai virus."Biopolymers. 51. 79-86 (1999)
Hiroshi Kido 等人:“人类粘液蛋白酶抑制剂及其突变体是针对甲型流感和仙台病毒感染的新型防御化合物。”生物聚合物。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Hiroshi Kido: "Cellular proteinases trigger the infectivity of the influenza A and Sendai viruses"Mol.Cells. 9(3). 235-244 (1999)
Hiroshi Kido:“细胞蛋白酶触发甲型流感病毒和仙台病毒的感染性”Mol.Cells。
- DOI:
- 发表时间:
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- 影响因子:0
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KIDO Hiroshi其他文献
KIDO Hiroshi的其他文献
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{{ truncateString('KIDO Hiroshi', 18)}}的其他基金
Allergy research prospect with new paradigm open up by the new sensitive allergen microarray
新型敏感过敏原微阵列开辟过敏研究新范式
- 批准号:
17K19662 - 财政年份:2017
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Study on the pathogenesis of severe influenza virus infection associated with cytokine storm and its effective treatment options
细胞因子风暴相关重症流感病毒感染发病机制及有效治疗方案研究
- 批准号:
16H05348 - 财政年份:2016
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Discovery of antigen-specific low affinity IgE in cord blood and the mechanisms of affinity maturation after birth for prevention of allergy
脐带血中抗原特异性低亲和力 IgE 的发现及其出生后亲和力成熟预防过敏的机制
- 批准号:
15K15371 - 财政年份:2015
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Screening of Flu Alarmin biomarkers of severe influenza virus infection and their confirmation in animal model
重症流感病毒感染Flu Alarmin生物标志物的筛选及动物模型验证
- 批准号:
25670466 - 财政年份:2013
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Pathogenicity of multiple organ failure induced by seasonal and highly pathogenic avian influenza virus infection and its therapeutic options
季节性高致病性禽流感病毒感染致多器官功能衰竭的致病性及治疗选择
- 批准号:
24249059 - 财政年份:2012
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Studies on real-time biomarker of illness severity inthe patients of critical illness and development of the diagnosis machine
危重症患者病情严重程度实时生物标志物研究及诊断机研制
- 批准号:
23659846 - 财政年份:2011
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Development of new therapeutics for a highly pathogenic influenza virus infection by inhibition of virus entry and multiplication
通过抑制病毒进入和增殖来开发高致病性流感病毒感染的新疗法
- 批准号:
21249061 - 财政年份:2009
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Systematic extraction of vocabulary used to express auditory impressions of utterances
系统地提取用于表达话语听觉印象的词汇
- 批准号:
19500177 - 财政年份:2007
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of voice montage system.
开发语音蒙太奇系统。
- 批准号:
16300061 - 财政年份:2004
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of new influenza virus treatments based an the findings of triggering proteases for influenza virus entry into the cells and on the findings of protease-activating receptors
基于触发流感病毒进入细胞的蛋白酶的发现以及蛋白酶激活受体的发现,开发新的流感病毒治疗方法
- 批准号:
13557014 - 财政年份:2001
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Scientific Research (B)