The molecular basis of PSGL-1-dependent viral replication and pathogenesis in enterovirus 71 infection

肠道病毒71感染中PSGL-1依赖性病毒复制和发病机制的分子基础

• 批准号: 22390092
• 负责人: SHIMIZU HIROYUKI
• 金额: $ 9.98万
• 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 (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390092/
• 关键词: エンテロウイルス; 受容体; エンテロウイルス71; PSGL-1; 感染モデル; 手足口病; レセプター; 病原性; 感染動物モデル; カニクイザル; ウイルス; 感染症

Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease, and causes various neurological diseases, including fatal encephalitis. In this study, we investigated the molecular basis of the interaction between EV71 and PSGL-1, a functional cellular receptor for EV71. We demonstrated that tyrosine sulfation at the N-terminal region of PSGL-1 plays a critical role in the PSGL-1-binding to EV71. An amino acid residue of the capsid protein VP1 of EV71 (VP1-145) controls virus tropism by changing the accessibility of VP1-244 to the sulfated N-terminus of PSGL-1, thus suggesting the involvement of VP1-145 in a PSGL-1-dependent viral replication and pathogenesis in EV71 infection.

肠道病毒71型(EV71)是手足口病的主要病原体，可引起多种神经系统疾病，包括致命性脑炎。在这项研究中，我们研究了EV71与PSGL-1相互作用的分子基础。PSGL-1是EV71的功能细胞受体。我们证明了PSGL-1 N-末端的酪氨酸硫酸化在PSGL-1与EV71结合的过程中起着关键作用。EV71衣壳蛋白VP1(VP1-145)的一个氨基酸残基通过改变VP1-244对PSGL-1硫化N末端的可及性来控制病毒嗜性，从而表明VP1-145参与了依赖PSGL-1的病毒复制和EV71感染的发病机制。

项目成果

Genetic analysis of PSGL-1-tropic enterovirus 71 isolates from clinical samples

临床样本中 PSGL-1 嗜性肠道病毒 71 株的遗传分析

• 发表时间: 2012
• 作者: Umami RN;Hosomi T;Nishimura Y;Shimizu H
• 通讯作者: Shimizu H

Characterization of cellular and viral factors involved in PSGL-1-dependent viral replication of enterovirus 71

肠道病毒 71 依赖 PSGL-1 的病毒复制所涉及的细胞和病毒因子的表征

• 发表时间: 2010
• 作者: Nishimura Y;et al.
• 通讯作者: et al.

Genetic and Phenotypic Diversity of Enterovirus 71

肠道病毒 71 型的遗传和表型多样性

• 作者: 奈良信雄;鈴木利哉;北村大介（分担）;鈴木留美子;Shimizu H
• 通讯作者: Shimizu H

Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in Northern Nigeria

• DOI: 10.1128/jvi.02954-12
• 发表时间: 2013-05-01
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Burns, Cara C.;Shaw, Jing;Kew, Olen
• 通讯作者: Kew, Olen

VP1-145 of enterovirus 71 is one of the determinants for pathogenicity in a cynomolgus monkey model

肠道病毒 71 型的 VP1-145 是食蟹猴模型致病性的决定因素之一

• 发表时间: 2014
• 作者: Kataoka C;Nishimura Y;Suzuki T;Kotani O;Iwata N;Nagata A;Ami Y;Shimizu H
• 通讯作者: Shimizu H