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
Degree grantor/typeNagasaki University (長崎大学)
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)
http://hdl.handle.net/10069/00041438
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2022-06-05T18:01:14+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション