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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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| 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: | 人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 高田 礼人
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