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PMID: 21907381 Published · ppublish English Journal Article

The Ebola virus glycoprotein mediates entry via a non-classical dynamin-dependent macropinocytic pathway.

Virology ·Vol. 419 ·No. 2 ·2011-10-25 ·Pages 72-83

Mulherkar N, Raaben M, de la Torre JC, Whelan SP, Chandran K

Abstract

Ebola virus (EBOV) has been reported to enter cultured cell lines via a dynamin-2-independent macropinocytic pathway or clathrin-mediated endocytosis. The route(s) of productive EBOV internalization into physiologically relevant cell types remain unexplored, and viral-host requirements for this process are incompletely understood. Here, we use electron microscopy and complementary chemical and genetic approaches to demonstrate that the viral glycoprotein, GP, induces macropinocytic uptake of viral particles into cells. GP's highly-glycosylated mucin domain is dispensable for virus-induced macropinocytosis, arguing that interactions between other sequences in GP and the host cell surface are responsible. Unexpectedly, we also found a requirement for the large GTPase dynamin-2, which is proposed to be dispensable for several types of macropinocytosis. Our results provide evidence that EBOV uses an atypical dynamin-dependent macropinocytosis-like entry pathway to enter Vero cells, adherent human peripheral blood-derived monocytes, and a mouse dendritic cell line.

MeSH Terms
Actins/metabolism Amiloride/analogs & derivatives,pharmacology Animals Cell Line Chlorocebus aethiops Dendritic Cells Dynamin II/antagonists & inhibitors,genetics,metabolism Ebolavirus/metabolism,physiology Humans Hydrazones/pharmacology Mice Microscopy, Electron Pinocytosis/drug effects Vero Cells Vesiculovirus/drug effects Viral Envelope Proteins/metabolism Virus Internalization/drug effects
Chemicals
Actins Hydrazones N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide Viral Envelope Proteins envelope glycoprotein, Ebola virus Amiloride Dynamin II ethylisopropylamiloride
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Mulherkar Nirupama
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Raaben Matthijs
de la Torre Juan Carlos
Whelan Sean P
Chandran Kartik
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Article Info
Journal
Virology
Abbr.
Virology
ISSN
1096-0341
DOI
10.1016/j.virol.2011.08.009
Published
2011-10-25
Epub
2011-00-09
Pages
72-83
Language
English
Region
United States
NLM ID
0110674
PMCID
PMC3177976
Subset
IM
Grants
NIAID NIH HHS · R01 AI081842-03 · United States
NIAID NIH HHS · U54 AI057159 · United States
NIAID NIH HHS · R01 AI088027 · United States
NIAID NIH HHS · R01 AI047140-06A1 · United States
NIAID NIH HHS · R01 AI047140 · United States
NIAID NIH HHS · R01 AI088027-02 · United States
NIAID NIH HHS · R01 AI081842 · United States
NIAID NIH HHS · R01 AI088027-01 · United States
NIAID NIH HHS · R01 AI081842-02 · United States
External Links
PubMed source DOI: 10.1016/j.virol.2011.08.009 PMC Full Text
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