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Investigation for signals and host factors related to paramyxovirus budding.

研究与副粘病毒出芽相关的信号和宿主因素。

基本信息

批准号：
15590418
负责人：
SAKAGUCHI Takemasa
金额：
$ 2.24万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590418/
关键词：
virus Sendai virus assembly budding virus-like particle M protein C protein AIP1 Alix 宿主因子

项目摘要

In the present project, we obtained the results described below.Firstly, we established a system to generate virus-like particles (VLPs) similar to Sendai virus (SeV) by co-transfecting multiple viral proteins. By using the system, we found that the accessory C protein had an ability to facilitate VLP release. We further demonstrated that the C protein interacted a host factor, AIP1/Alix, and that the interaction was essential for the VLP facilitation.Secondly, we confirmed that the M protein is a driving force for the particle release from cells, and we identified a late domain motif in the M protein, which was further shown to interact with AIP1/Alix. Neither Tsg101 nor Nedd4 appeared to be involved in the M protein function, but ubiquitin and Vps4A were involved in it.Thus, both of the M and C proteins are important for virus budding probably by interacting AIP1/Alix. The interaction was presumed to recruit the endosome-sorting complex required for transport (ESCRT) to virus budding. We further identified amino acid motifs for the interaction between the SeV proteins and AIP/Alix, and will generate viruses carrying the mutations incompetent to binding with AIP1/Alix to confirm and extend our results. As described, viral proteins important virus budding, viral protein motifs for the function, and related host factors are being clarified.

在本项目中，我们获得了以下结果。首先，我们建立了一个系统，通过共转染多种病毒蛋白来产生类似于仙台病毒（SeV）的病毒样颗粒（VLP）。通过使用该系统，我们发现辅助C蛋白具有促进VLP释放的能力。我们进一步证明了C蛋白与宿主因子AIP 1/阿利克斯相互作用，这种相互作用是VLP易化的必要条件;其次，我们证实了M蛋白是颗粒从细胞释放的驱动力，并且我们鉴定了M蛋白中的一个晚期结构域基序，它进一步被证明与AIP 1/阿利克斯相互作用。Tsg 101和Nedd 4均不参与M蛋白的功能，但泛素和Vps 4A参与了M蛋白的功能，因此M蛋白和C蛋白可能通过与AIP 1/阿利克斯相互作用而对病毒出芽起重要作用。这种相互作用被假定为募集转运所需的内体分选复合物（ESCRT）至病毒出芽。我们进一步鉴定了SeV蛋白与AIP/阿利克斯之间相互作用的氨基酸基序，并将产生携带不能与AIP 1/阿利克斯结合的突变的病毒，以证实和扩展我们的结果。如所述，病毒蛋白质对病毒出芽的重要性、病毒蛋白质基序的功能以及相关的宿主因子正在被阐明。

项目成果

期刊论文数量（30）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

AIP/Alix is a binding partner of Sendai virus C protein and facilitates virus budding.

AIP/Alix 是仙台病毒 C 蛋白的结合伙伴，促进病毒出芽。

DOI：
发表时间：
2005
期刊：
Journal of Virology 79
影响因子：
0
作者：
Sakaguchi;T. et al.
通讯作者：
T. et al.

Safety and growth suppressive effect of intra-hepatic arterial infection of AdCMV-p53 combined with CDDP to rat liver metastatic tumors.

AdCMV-p53联合CDDP肝内动脉感染对大鼠肝转移瘤的安全性及生长抑制作用

DOI：
发表时间：
2003
期刊：
Journal Experimental & Clinical Cancer Research 22
影响因子：
0
作者：
Okimoto;T. et al.
通讯作者：
T. et al.

Paramyxovirus Sendai virus-like particle formation by expression of multiple viral proteins and acceleration of its release by C protein.

DOI：
10.1016/j.virol.2004.04.019
发表时间：
2004-07
期刊：
Virology
影响因子：
3.7
作者：
Fumihiro Sugahara;T. Uchiyama;Hitoshi Watanabe;Y. Shimazu;M. Kuwayama;Y. Fujii;K. Kiyotani;A. Adachi;N. Kohno;Tetsuya Yoshida;T. Sakaguchi
通讯作者：
Fumihiro Sugahara;T. Uchiyama;Hitoshi Watanabe;Y. Shimazu;M. Kuwayama;Y. Fujii;K. Kiyotani;A. Adachi;N. Kohno;Tetsuya Yoshida;T. Sakaguchi

Characterization of the amino acid residues of Sandai Virus C protein that are critically involved in its interferon antagonism and RNA synthesis down-regulation.

桑代病毒 C 蛋白氨基酸残基的表征，这些残基在干扰素拮抗作用和 RNA 合成下调中发挥着重要作用。