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Title	en Ebolavirus Is Internalized into Host Cells via Macropinocytosis in a Viral Glycoprotein-Dependent Manner
Creator	en Nanbo, Asuka NRID 1000060359487 en Imai, Masaki en Watanabe, Shinji en Noda, Takeshi en Takahashi, Kei en Neumann, Gabriele en Halfmann, Peter en Kawaoka, Yoshihiro
Accessrights	open access
Rights	http://creativecommons.org/licenses/by/3.0/ en Creative Commons Attribution 3.0 Unported
Subject	NDC 493
Description	Abstract en Ebolavirus (EBOV) is an enveloped, single-stranded, negative-sense RNA virus that causes severe hemorrhagic fever with mortality rates of up to 90% in humans and nonhuman primates. Previous studies suggest roles for clathrin- or caveolae-mediated endocytosis in EBOV entry; however, ebolavirus virions are long, filamentous particles that are larger than the plasma membrane invaginations that characterize clathrin- or caveolae-mediated endocytosis. The mechanism of EBOV entry remains, therefore, poorly understood. To better understand Ebolavirus entry, we carried out internalization studies with fluorescently labeled, biologically contained Ebolavirus and Ebolavirus-like particles (Ebola VLPs), both of which resemble authentic Ebolavirus in their morphology. We examined the mechanism of Ebolavirus internalization by real-time analysis of these fluorescently labeled Ebolavirus particles and found that their internalization was independent of clathrin or caveolae-mediated endocytosis, but that they co-localized with sorting nexin (SNX) 5, a marker of macropinocytosis-specific endosomes (macropinosomes). Moreover, the internalization of Ebolavirus virions accelerated the uptake of a macropinocytosis-specific cargo, was associated with plasma membrane ruffling, and was dependent on cellular GTPases and kinases involved in macropinocytosis. A pseudotyped vesicular stomatitis virus possessing the Ebolavirus glycoprotein (GP) also co-localized with SNX5 and its internalization and infectivity were affected by macropinocytosis inhibitors. Taken together, our data suggest that Ebolavirus is internalized into cells by stimulating macropinocytosis in a GP-dependent manner. These findings provide new insights into the lifecycle of Ebolavirus and may aid in the development of therapeutics for Ebolavirus infection.
Publisher	en Public Library of Science
Date	Issued2010-09-23
Language	eng
Resource Type	journal article
Version Type	VoR
Identifier	HDL http://hdl.handle.net/2115/50165
Relation	isIdenticalTo DOI https://doi.org/10.1371/journal.ppat.1001121
Journal	EISSN 1553-7374 en PLoS Pathogens Volume Number6 Issue Number9 Page Starte1001121
File	fulltext PLoSP6-9_e1001121.pdf 8.48 MB (application/pdf) Issued2010-09-23
Oaidate	2023-07-26