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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| Vydáno v: | Virology (New York, N.Y.) Ročník 419; číslo 2; s. 72 - 83 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
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Elsevier Inc
25.10.2011
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| ISSN: | 0042-6822, 1096-0341, 1096-0341 |
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| 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. |
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| AbstractList | 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. 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. 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.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. |
| Author | Raaben, Matthijs de la Torre, Juan Carlos Chandran, Kartik Whelan, Sean P. Mulherkar, Nirupama |
| AuthorAffiliation | 1 Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461 2 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115 3 Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037 |
| AuthorAffiliation_xml | – name: 2 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115 – name: 3 Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037 – name: 1 Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461 |
| Author_xml | – sequence: 1 givenname: Nirupama surname: Mulherkar fullname: Mulherkar, Nirupama organization: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA – sequence: 2 givenname: Matthijs surname: Raaben fullname: Raaben, Matthijs organization: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA – sequence: 3 givenname: Juan Carlos surname: de la Torre fullname: de la Torre, Juan Carlos organization: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA – sequence: 4 givenname: Sean P. surname: Whelan fullname: Whelan, Sean P. organization: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA – sequence: 5 givenname: Kartik surname: Chandran fullname: Chandran, Kartik email: kartik.chandran@einstein.yu.edu organization: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21907381$$D View this record in MEDLINE/PubMed https://www.osti.gov/biblio/21587894$$D View this record in Osti.gov |
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| Keywords | 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 |
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| Snippet | Ebola virus (EBOV) has been reported to enter cultured cell lines via a dynamin-2-independent macropinocytic pathway or clathrin-mediated endocytosis. The... Abstract Ebola virus (EBOV) has been reported to enter cultured cell lines via a dynamin-2-independent macropinocytic pathway or clathrin-mediated endocytosis.... |
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| SubjectTerms | 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 |
| Title | The Ebola virus glycoprotein mediates entry via a non-classical dynamin-dependent macropinocytic pathway |
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