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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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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/64771

Title: Fcγ-receptor IIa-mediated Src Signaling Pathway Is Essential for the Antibody-Dependent Enhancement of Ebola Virus Infection
Authors: Furuyama, Wakako Browse this author
Marzi, Andrea Browse this author
Carmody, Aaron B. Browse this author
Maruyama, Junki Browse this author
Kuroda, Makoto Browse this author
Miyamoto, Hiroko Browse this author
Nanbo, Asuka Browse this author →KAKEN DB
Manzoor, Rashid Browse this author
Yoshida, Reiko Browse this author
Igarashi, Manabu Browse this author →KAKEN DB
Feldmann, Heinz Browse this author
Takada, Ayato Browse this author →KAKEN DB
Issue Date: 30-Dec-2016
Publisher: PLOS
Journal Title: PLoS Pathogens
Volume: 12
Issue: 12
Start Page: e1006139
Publisher DOI: 10.1371/journal.ppat.1006139
Abstract: 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.
Rights: https://creativecommons.org/publicdomain/zero/1.0/
Type: article
URI: http://hdl.handle.net/2115/64771
Appears in Collections:人獣共通感染症リサーチセンター (Research Center for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 高田 礼人

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