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Fcγ-receptor IIa-mediated Src Signaling Pathway Is Essential for the Antibody-Dependent Enhancement of Ebola Virus Infection


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タイトル: Fcγ-receptor IIa-mediated Src Signaling Pathway Is Essential for the Antibody-Dependent Enhancement of Ebola Virus Infection
著者: Furuyama, Wakako 著作を一覧する
Marzi, Andrea 著作を一覧する
Carmody, Aaron B. 著作を一覧する
Maruyama, Junki 著作を一覧する
Kuroda, Makoto 著作を一覧する
Miyamoto, Hiroko 著作を一覧する
Nanbo, Asuka 著作を一覧する
Manzoor, Rashid 著作を一覧する
Yoshida, Reiko 著作を一覧する
Igarashi, Manabu 著作を一覧する
Feldmann, Heinz 著作を一覧する
Takada, Ayato 著作を一覧する
発行日: 2016年12月30日
出版者: PLOS
誌名: PLoS Pathogens
巻: 12
号: 12
開始ページ: e1006139
出版社 DOI: 10.1371/journal.ppat.1006139
抄録: Antibody-dependent enhancement (ADE) of Ebola virus (EBOV) infection has been demonstrated in vitro, raising concerns about the detrimental potential of some anti-EBOV antibodies. ADE has been described for many viruses and mostly depends on the cross-linking of virus-antibody complexes to cell surface Fc receptors, leading to enhanced infection. However, little is known about the molecular mechanisms underlying this phenomenon. Here we show that Fc gamma-receptor IIa (Fc gamma RIIa)-mediated intracellular signaling through Src family protein tyrosine kinases (PTKs) is required for ADE of EBOV infection. We found that deletion of the Fc gamma RIIa cytoplasmic tail abolished EBOV ADE due to decreased virus uptake into cellular endosomes. Furthermore, EBOV ADE, but not non-ADE infection, was significantly reduced by inhibition of the Src family protein PTK pathway, which was also found to be important to promote phagocytosis/macropinocytosis for viral uptake into endosomes. We further confirmed a significant increase of the Src phosphorylation mediated by ADE. These data suggest that antibody-EBOV complexes bound to the cell surface Fc gamma RIIa activate the Src signaling pathway that leads to enhanced viral entry into cells, providing a novel perspective for the general understanding of ADE of virus infection.
資料タイプ: article
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 高田 礼人


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