Dissect the role of hepatitis C virus NS2 protein in virus assembly

剖析丙型肝炎病毒NS2蛋白在病毒组装中的作用

• 批准号: 21590519
• 负责人: SUZUKI Ryosuke
• 金额: $ 2.83万
• 依托单位: National Institute of Infectious Diseases
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590519/
• 关键词: HCV; NS2; 粒子形成; 感染性粒子; 宿主因子; 感染性

Hepatitis C virus(HCV) nonstructural protein 2(NS2) is a membrane-associated cysteine autoprotease that mediates cleavage of its own carboxyl terminus from NS3.In addition to its role in polyprotein processing, emerging evidence indicates that NS2plays crucial role in assembly of infectious virus particle. However, biological significance of NS2in the HCV assembly remains unclear. In this study, we screened human liver cDNA libraries by split-ubiquitin membrane yeast two-hybrid assay using NS2as a bait, and identified several NS2-interacting proteins. Following siRNA screening identified a membrane-associated cellular protein that is involved in HCV production. Gene silencing of the host factor resulted in no effect on the entry and RNA replication of HCV, suggesting that this host factor is involved in HCV assembly step. Interaction of the host factor with NS2 in mammalian cells was confirmed. Finding of this study may provide important information for understanding the molecular mechanism of assembly and formation of infectious HCV particles.

丙型肝炎病毒（HCV）非结构蛋白2（NS2）是一种膜结合的半胱氨酸蛋白酶，它介导NS3的羧基端裂解，除了参与多聚蛋白的加工外，NS2还参与病毒颗粒的组装。然而，NS2在HCV组装中的生物学意义尚不清楚。本研究以NS2为诱饵，利用分裂泛素膜酵母双杂交技术筛选人肝脏cDNA文库，并鉴定了几个与NS2相互作用的蛋白。随后的siRNA筛选鉴定了参与HCV产生的膜相关细胞蛋白。宿主因子的基因沉默对HCV的进入和RNA复制没有影响，表明该宿主因子参与了HCV的组装步骤。证实了宿主因子与哺乳动物细胞中的NS2的相互作用。本研究结果为深入了解HCV感染性颗粒的组装和形成的分子机制提供了重要信息。

项目成果

Identification of novel NS5A-associated proteins in the host-cell membrane fraction and their role in HCV life cycle

宿主细胞膜组分中新型 NS5A 相关蛋白的鉴定及其在 HCV 生命周期中的作用

• 发表时间: 2011
• 作者: K Goto;他
• 通讯作者: 他

Isolation of a highly infectious hepatitis C virus with adaptive mutations

具有适应性突变的高传染性丙型肝炎病毒的分离

• 发表时间: 2011
• 作者: M Fukasawa;他
• 通讯作者: 他

Signal peptidase complex 1 participates in the assembly of hepatitis C virus through an interaction with NS2

信号肽酶复合物 1 通过与 NS2 相互作用参与丙型肝炎病毒的组装

• 发表时间: 2011
• 作者: R. Suzuki;T. Suzuki;K. Saito;M. Matsuda;K. Watashi;Y. Matsuura;T. Wakita;H. Aizaki
• 通讯作者: H. Aizaki

Identification of host factor that interacts with hepatitis C virus NS2 protein and is involved in the viral assembly

鉴定与丙型肝炎病毒 NS2 蛋白相互作用并参与病毒组装的宿主因子

• 发表时间: 2011
• 作者: Suzuki R;Suzuki T;Saito K;Matsuda M;Watashi K;Matsuura Y;Wakita T;Aizaki H
• 通讯作者: Aizaki H

Evaluation of Hepatitis C Virus Core Antigen Assays in Detecting Recombinant Viral Antigens of Various Genotypes

• DOI: 10.1128/jcm.01437-09
• 发表时间: 2009-12-01
• 期刊: JOURNAL OF CLINICAL MICROBIOLOGY
• 影响因子: 9.4
• 作者: Saeed, Mohsan;Suzuki, Ryosuke;Suzuki, Tetsuro
• 通讯作者: Suzuki, Tetsuro