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

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 proc...

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Vydané v:	Virology (New York, N.Y.) Ročník 419; číslo 2; s. 72 - 83
Hlavní autori:	Mulherkar, Nirupama, Raaben, Matthijs, de la Torre, Juan Carlos, Whelan, Sean P., Chandran, Kartik
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Elsevier Inc 25.10.2011
Predmet:	60 APPLIED LIFE SCIENCES Actins - metabolism Amiloride - analogs & derivatives Amiloride - pharmacology ANIMALS Antigen presenting cells ANTIGENS BIOLOGICAL MATERIALS BLOOD BLOOD CELLS BODY FLUIDS CARBOHYDRATES Cell Line Chlorocebus aethiops CRYSTALS cultured cells DENDRITES Dendritic Cells Dynamin Dynamin II - antagonists & inhibitors Dynamin II - genetics Dynamin II - metabolism Ebola virus Ebolavirus Ebolavirus - metabolism Ebolavirus - physiology ELECTRON MICROSCOPY Endocytosis Filovirus Glycoprotein GLYCOPROTEINS guanosinetriphosphatase Humans Hydrazones - pharmacology Infectious Disease LEUKOCYTES Macropinocytosis MAMMALS MATERIALS MICE MICROORGANISMS MICROSCOPY Microscopy, Electron MONOCYTES mucins ORGANIC COMPOUNDS Pak-1 PARASITES PARTICLES Pinocytosis - drug effects PROTEINS RODENTS SACCHARIDES UPTAKE Vero Cells VERTEBRATES Vesicular stomatitis virus Vesiculovirus - drug effects Viral entry Viral Envelope Proteins - metabolism Viral infection Virus Internalization - drug effects Virus-like particles VIRUSES Viral entry Dendritic cells Glycoprotein Antigen presenting cells Pak-1 Viral infection Virus-like particles Ebola virus Vesicular stomatitis virus Endocytosis Monocytes Dynamin Filovirus Macropinocytosis
ISSN:	0042-6822, 1096-0341, 1096-0341
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0042-6822 1096-0341 1096-0341
DOI:	10.1016/j.virol.2011.08.009