课题基金 / 基金详情

Molecular mechanism of measles virus-induced immunosuppression

Molecular mechanism of measles virus-induced immunosuppression
麻疹病毒诱导免疫抑制的分子机制
批准号:
06670322
负责人:
YANAGI Yusuke
金额:
$1.34万
依托单位国家:
日本
项目类别:
Grant-in-Aid for General Scientific Research (C)
财政年份:
1994
资助国家:
日本
项目状态:
已结题
起止时间:
1994 至 1995

项目摘要

项目成果

YANAGI Yusuke的其他基金

相似基金

相关文献

中文摘要
翻译
小鼠成纤维细胞系(L,NIH 3 T3)支持麻疹病毒(MV)的低水平复制。这些成纤维细胞从未形成多核巨细胞,这是MV感染的特征性细胞病变效应。我们获得了稳定表达编码人CD 46(最近鉴定的MV受体)的基因的L细胞转染子。在用MV感染后,这些转染子产生20倍多的MV,变得比亲本L细胞对MV敏感100倍,并形成合胞体。为了确定CD 46中对受体功能至关重要的结构域,产生了几种缺失突变体,其缺乏CD 46的胞质区或四个短共有重复序列(SCR)中的每一个。发现缺乏SCR 1或SCR 2的突变体不作为受体,表明SCR 1或SCR 2对于作为MV受体的功能是不可缺少的。在这些结果的基础上,我们生产了表达人CD 46的转基因小鼠作为动物模型,以研究MV感染期间观察到的免疫抑制。我们目前正在测试这些小鼠是否对MV敏感,是否出现任何临床症状。我们还研究了MV抑制T细胞体外增殖的机制。与表达MV糖蛋白而不产生感染性MV的细胞共培养并不导致对促分裂原诱导的T细胞增殖的抑制,表明通过在MV感染的细胞上表达的MV糖蛋白和未感染的细胞上的表面分子的细胞-细胞相互作用不足以引起对T细胞增殖的抑制。
英文摘要
Mouse fibroblast cell lines (L, NIH3T3) supported a low level of measles virus (MV) replication. These fibroblasts never formed multinucleated giant cells, a characteristic cytopathic effect of MV infection. We derived L cell transfectants stably expressing the gene encoding the human CD46, the recently identified MV receptor. Upon infection with MV, these transfectants produced 20 fold more MV, became 100 time more sensitive to MV than the parental L cells, and developed syncytia. To determine the domain (s) in CD46 essential for the receptor function, several deletion mutants were generated that lacked the cytoplasmic region or each one of the four short consensus repeat (SCR) of CD46. Mutants lacking SCR1 or SCR2 were found not to act as the receptor, indicating that SCR1 or SCR2 are indispensable for the function as the MV receptor. On the basis of these results, we produced transgenic mice expressing the human CD46 as an animal model to study immunosuppression observed during MV infection. We are currently testing whether these mice are susceptible to MV, and develop any clinical signs.We also examined the mechanism by which MV inhibitits thein vitro proliferation of T cells. Coculture with cells expressing MV glycoproteins without producing infectious MV did not lead to the inhibition of the mitogen-induced T cell proliferation, indicating that the cell-cell interaction through MV glycoproteins expressed on MV-infected cells and surface molecules on uninfected cells is not sufficient to cause the inhibition of T cell proliferation.
期刊论文(36)
专著(0)
科研奖励(0)
会议论文
Sakae, H.et al.: "L cell clone developing plaques upon infection with measles virus (Edmonston strain)" Archives of Virology. 139. 427-430 (1994)
Sakae, H.et al.:“感染麻疹病毒(埃德蒙斯顿株)后 L 细胞克隆形成斑块”病毒学档案。
DOI: --
发表时间:
期刊:
影响因子: --
作者: []
通讯作者:
1995: "117-123" Yanagi, Y.Measles virus receptor CD46 (in Japanese).
1995:“117-123”Yanagi,Y.麻疹病毒受体CD46(日语)。
DOI: --
发表时间:
期刊:
影响因子: --
作者: []
通讯作者:
Yanagi, Y.: "Measles virus infects mouse fibroblast cell lines, but its multiplication is severely restricted in the absence of CD46." Archives of Virology. 138. 39-53 (1994)
Yanagi, Y.:“麻疹病毒感染小鼠成纤维细胞系,但在缺乏 CD46 的情况下其增殖受到严重限制。”
DOI: --
发表时间:
期刊:
影响因子: --
作者: []
通讯作者:
DOI: --
发表时间:
期刊:
影响因子: --
作者: []
通讯作者:
14
    Mechanism of measles virus spread in the brain
    Development of new therapy for congenital metabolic disorders using functional three-dimensional liver structures constructed by stem cells from human exfoliated deciduous teeth
    • 批准号:
      24592696
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $3.08万
    • 财政年份:
      2012
    • 负责人:
      YANAGI Yusuke
    • 依托单位:
    Measles pathogenesis as studied using animal models
    • 批准号:
      21249032
    • 项目类别:
      Grant-in-Aid for Scientific Research (A)
    • 资助金额:
      $29.62万
    • 财政年份:
      2009
    • 负责人:
      YANAGI Yusuke
    • 依托单位:
    Analysis of measles pathogenesis using the mouse model expressing measles virus receptor SLAM and recombinant viruses
    • 批准号:
      17209016
    • 项目类别:
      Grant-in-Aid for Scientific Research (A)
    • 资助金额:
      $32.45万
    • 财政年份:
      2005
    • 负责人:
      YANAGI Yusuke
    • 依托单位:
    海外基金