Analysis of virus-receptor interaction and its application in veterinary science

病毒-受体相互作用分析及其在兽医学中的应用

基本信息

  • 批准号:
    11460148
  • 负责人:
  • 金额:
    $ 10.11万
  • 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:
    1999
  • 资助国家:
    日本
  • 起止时间:
    1999 至 2001
  • 项目状态:
    已结题

项目摘要

We have investigated the interaction of mouse hepatitis virus (MHV) and its receptor CEACAM1 (MHVR) by using soluble form of MHVR (soMHVR). soMHVR1 derived from MHV-susceptible BALB/c mouse showed high affinity and neutralizing activity to MHV, while soMHVR2 isolated from MHV-resistant SJL mouse was low in affinity and neutralization activity. We have isolated mutant virus resistant to neutralization (srr7) by soMHVR1 from MHV-JHMV. Srr7 infected as efficiently as wild type JHMV to cells expressing MHVR1, but did more than 2 logs less efficiently than wt virus to cells expressing MHVR2.This inefficient infection of srr7 was revealed to be due to its low fusogenicity, namely low capability to enter into these cells. These results suggested that the binding ofMHVR2 to wild type S protein triggered its conformational change, while it failed to do so for srr7 S proteins. We have also found that soMHVR1 activated or potentiated MHV infection to MHVR-deficient cells. This implied that binding of soMHVR converted fusion-negative S protein to fusion-positive phenotype. Using this system, we can further investigate in cell-free system the interaction of MHV and receptor as well as dynamics MHV particles following its interaction with receptor. Env protein ofmurine leukemia virus Fv-4r plays an important role for the resistance of mice to various leukemia viruses. We have conferred the resistance against leukemia virus to otherwise susceptible mice by expressing Env using retrovirus vectors. We have developed a highly pathogenic influenza A virus by passaging an avirulent virus through chickens. This conversion was accompanied with the mutations in HA protein, which resulted in enhanced cleavability of the protein. This suggested that HA cleavability influenced the pathogenicity of influenza virus.
用可溶性的CEACAM1受体(SoMHVR)研究了小鼠肝炎病毒(MHV)与其受体CEACAM1(MHVR)的相互作用。从MHV敏感的BALB/c小鼠分离的soMHVR1对MHV具有高亲和力和中和活性,而从MHV耐药的SJL小鼠分离的soMHVR2具有低的亲和力和中和活性。我们从MHV-JHMV中分离到了耐soMHVR1中和突变病毒(Srr7)。Srr7与野生型JHMV对表达MHVR1的细胞的感染效率相当,但对表达MHVR2的细胞的感染效率比wt病毒低2倍以上。srr7的低效感染是由于其低融合活性,即进入细胞的能力低所致。这些结果表明,MHVR2与野生型S蛋白的结合引发了其构象变化,而Srr7 S蛋白则未发生构象变化。我们还发现,soMHVR1激活或增强了MHVR缺陷细胞的MHV感染。这表明,soMHVR的结合将融合阴性的S蛋白转化为融合阳性的表型。利用该系统,我们可以在无细胞体系中进一步研究MHV与受体的相互作用,以及MHV颗粒在与受体相互作用后的动力学。小鼠白血病病毒FV-4r的env蛋白在小鼠对多种白血病病毒的抵抗力中起着重要作用。我们通过逆转录病毒载体表达Env,使易感小鼠对白血病病毒产生抵抗力。我们通过将一种无毒病毒通过鸡来传播,从而开发出一种高致病性的甲型流感病毒。这种转化伴随着HA蛋白的突变,导致蛋白的切割能力增强。这表明,HA的裂解能力影响流感病毒的致病性。

项目成果

期刊论文数量(76)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Ito Y, Kawaoka Y, Nomura A et al.: "Receptor specificity on influenza A viruses from sea mammals correlates with lung sialyoligosaccharides in theses animals."J. Vet. Med. Sci. 61. 955-958 (1999)
Ito Y、Kawaoka Y、Nomura A 等人:“来自海洋哺乳动物的甲型流感病毒的受体特异性与这些动物的肺唾液酸寡糖相关。”
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    0
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  • 通讯作者:
Yamada, YK., Yabe, M., Ohtsuki, T., Taguchi, F.: "Unique N-linked ghycosylation of HHV-2 membrane protein at the conserved O-linked glycosy laticn site in murine coronaviruses"Virus Research. (in press). (2000)
Yamada, YK.、Yabe, M.、Ohtsuki, T.、Taguchi, F.:“HHV-2 膜蛋白在鼠冠状病毒中保守的 O-连接糖基乳糖位点上的独特 N-连接糖基化”病毒研究。
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    0
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  • 通讯作者:
Taguchi, F.,: "Matsuyama, S., Saeki, K."Difference in Bgp-independent fusion activity among mouse hepatitis viruses. 144. 2041-2050 (1999)
Taguchi, F.,:“Matsuyama, S., Saeki, K.”小鼠肝炎病毒之间不依赖于 Bgp 的融合活性的差异。
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  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Itch,T.,Suzuki,Y.,Kawaoka,Y. et al.: "Recognition of N-glycolylneuraminic acid linked to galactose by α2,3 linkage associated with intestinal replication of influenza A virus in ducks."Journal of Virology. 74. 9300-9305 (2000)
Itch, T.、Suzuki, Y.、Kawaoka, Y. 等人:“通过 α2,3 连接识别与鸭甲型流感病毒肠道复制相关的 N-乙醇酰神经氨酸。”病毒学杂志 74。 .9300-9305 (2000)
  • DOI:
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    0
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Ito, T.et al.: "Virulent influenza A virus induces apoptosis of vascular epithelium in chicken in vivo infection"Virus Research. (in press). (2001)
Ito, T.等人:“强毒甲型流感病毒在体内感染鸡体内诱导血管上皮细胞凋亡”病毒研究。
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    0
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TAGUCHI Fumihiro其他文献

TAGUCHI Fumihiro的其他文献

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{{ truncateString('TAGUCHI Fumihiro', 18)}}的其他基金

Studies on receptor-independent infection of coronaviruses and its implication in the pathogenesis
冠状病毒的受体非依赖性感染及其在发病机制中的意义的研究
  • 批准号:
    19390135
  • 财政年份:
    2007
  • 资助金额:
    $ 10.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular analysis of cell entry of SARS coronavirus
SARS冠状病毒进入细胞的分子分析
  • 批准号:
    17390138
  • 财政年份:
    2005
  • 资助金额:
    $ 10.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Replication and gene expression of SARS coronavirus and other animal coronaviruses
SARS冠状病毒和其他动物冠状病毒的复制和基因表达
  • 批准号:
    16017308
  • 财政年份:
    2004
  • 资助金额:
    $ 10.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas
Production of MHV-resistance mouse by embryo technology
利用胚胎技术生产抗MHV小鼠
  • 批准号:
    08558089
  • 财政年份:
    1996
  • 资助金额:
    $ 10.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Identification of receptor-binding site of the mouse hepatitis virus spike protein
小鼠肝炎病毒刺突蛋白受体结合位点的鉴定
  • 批准号:
    07660413
  • 财政年份:
    1995
  • 资助金额:
    $ 10.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular biological studies on the neurovirulence of murine coronavirus
鼠冠状病毒神经毒力的分子生物学研究
  • 批准号:
    02660322
  • 财政年份:
    1990
  • 资助金额:
    $ 10.11万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
A trial to convert the mouse susceptible to mouse hepahtis virus to resistant one by anti-sense RNA
反义RNA将小鼠肝炎病毒易感小鼠转为耐药小鼠的试验
  • 批准号:
    62580037
  • 财政年份:
    1987
  • 资助金额:
    $ 10.11万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
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