Ebola Virus GP Activates Endothelial Cells via Host Cytoskeletal Signaling Factors

• Material Type: 博士論文
• Title: Ebola Virus GP Activates Endothelial Cells via Host Cytoskeletal Signaling Factors
• Author/Editor: Moni , Mpia Benedicte
• Author Heading: Moni , Mpia Benedicte
• Publication, Distribution, etc.: MDPI
• Publication Date: 2022-03-18
• Publication Date (W3CDTF): 2022-03-18
• Alternative Title: エボラウイルスGPは宿主の細胞骨格シグナル伝達因子を介して内皮細胞を活性化する
• Periodical title: Viruses
• No. or year of volume/issue: 14 1
• Volume: 14
• Issue: 1
• Pages: 142-
• ISSN (Periodical Title): ISSN : 1999-4915
• Degree grantor/type: Nagasaki University (長崎大学)
• Date Granted: 2022-03-18
• Dissertation Number: 甲医歯薬第1435号
• Degree Type: 博士(医学)
• Text Language Code: eng
• Subject Heading: Ebola GP; ICAM-1; virus–host interactions; cytoskeletal signaling; focal adhesion kinase; TNF-α; host factor; antivirals; micropinocytosis; Rho signaling pathway
• Target Audience: 一般
• Note (General): Ebola virus disease (EVD) is a lethal disease caused by the highly pathogenic Ebola virus (EBOV), and its major symptoms in severe cases include vascular leakage and hemorrhage. These symptoms are caused by abnormal activation and disruption of endothelial cells (ECs) whose mediators include EBOV glycoprotein (GP) without the need for viral replication. However, the detailed molecular mechanisms underlying virus–host interactions remain largely unknown. Here, we show that EBOV-like particles (VLPs) formed by GP, VP40, and NP activate ECs in a GP-dependent manner, as demonstrated by the upregulation of intercellular adhesion molecules-1 (ICAM-1) expression. VLPs-mediated ECs activation showed a different kinetic pattern from that of TNF-α-mediated activation and was associated with apoptotic ECs disruption. In contrast to TNF-α, VLPs induced ICAM-1 overexpression at late time points. Furthermore, screening of host cytoskeletal signaling inhibitors revealed that focal adhesion kinase inhibitors were found to be potent inhibitors of ICAM-1 expression mediated by both TNF-α and VLPs. Our results suggest that EBOV GP stimulates ECs to induce endothelial activation and dysfunction with the involvement of host cytoskeletal signaling factors, which represent potential therapeutic targets for EVD.; 長崎大学学位論文 学位記番号:博(医歯薬)甲第1435号 学位授与年月日:令和4年3月18日; Author: Benedicte Mpia Moni, Yasuteru Sakurai and Jiro Yasuda; Citation: Viruses, 14(1), art.no. 142; 2022; identifier:Nagasaki University (長崎大学), 博士(医学) (2022-03-18)
• Source: https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27417&item_no=1&attribute_id=70&file_no=1 （fulltext）; https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27417&item_no=1&attribute_id=70&file_no=1
• Access Restrictions: インターネット公開
• Rights (production): © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
• Related Material: http://hdl.handle.net/10069/00041438
• Related Material (DOI): 10.3390/v14010142
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 長崎大学 : 長崎大学学術研究成果リポジトリ