Ebola Virus Enters Host Cells by Macropinocytosis and Clathrin-Mediated Endocytosis
| Autor: | Andrea Marzi, Paulina Aleksandrowicz, Thomas Hoenen, Nadine Beimforde, Stephan Becker, Nadine Biedenkopf, Heinz Feldmann, Hans-Joachim Schnittler |
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| Rok vydání: | 2011 |
| Předmět: |
viruses
Caveolin 1 Virus Replication Endocytosis Clathrin Cell Line Amiloride VP40 Viral entry Caveolae Viral Biology Animals Humans Immunology and Allergy Gene Silencing RNA Small Interfering Dynamin biology Pinocytosis Epithelial Cells Receptor-mediated endocytosis Virus Internalization Bridged Bicyclo Compounds Heterocyclic Ebolavirus Actins Cell biology Androstadienes Infectious Diseases Host-Pathogen Interactions biology.protein Thiazolidines Wortmannin Signal Transduction |
| Zdroj: | The Journal of Infectious Diseases. 204:S957-S967 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jir326 |
| Popis: | Virus entry into host cells is the first step of infection and a crucial determinant of pathogenicity. Here we show that Ebola virus-like particles (EBOV-VLPs) composed of the glycoprotein GP(1,2) and the matrix protein VP40 use macropinocytosis and clathrin-mediated endocytosis to enter cells. EBOV-VLPs applied to host cells induced actin-driven ruffling and enhanced FITC-dextran uptake, which indicated macropinocytosis as the main entry mechanism. This was further supported by inhibition of entry through inhibitors of actin polymerization (latrunculin A), Na(+)/H(+)-exchanger (EIPA), and PI3-kinase (wortmannin). A fraction of EBOV-VLPs, however, colocalized with clathrin heavy chain (CHC), and VLP uptake was reduced by CHC small interfering RNA transfection and expression of the dominant negative dynamin II-K44A mutant. In contrast, we found no evidence that EBOV-VLPs enter cells via caveolae. This work identifies macropinocytosis as the major, and clathrin-dependent endocytosis as an alternative, entry route for EBOV particles. Therefore, EBOV seems to utilize different entry pathways depending on both cell type and virus particle size. |
| Databáze: | OpenAIRE |
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