English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/111240
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

African swine fever virus uses macropinocytosis to enter host cells

AuthorsSánchez, Elena G. ; Quintas, Ana ; Pérez-Núñez, Daniel ; Nogal París, María Luisa ; Barroso, Susana ; Carrascosa, Ángel L.; Revilla Novella, Yolanda
Issue Date2012
PublisherPublic Library of Science
CitationPLoS Pathogens 2012; 8 (6): e1002754
AbstractAfrican swine fever (ASF) is caused by a large and highly pathogenic DNA virus, African swine fever virus (ASFV), which provokes severe economic losses and expansion threats. Presently, no specific protection or vaccine against ASF is available, despite the high hazard that the continued occurrence of the disease in sub-Saharan Africa, the recent outbreak in the Caucasus in 2007, and the potential dissemination to neighboring countries, represents. Although virus entry is a remarkable target for the development of protection tools, knowledge of the ASFV entry mechanism is still very limited. Whereas early studies have proposed that the virus enters cells through receptor-mediated endocytosis, the specific mechanism used by ASFV remains uncertain. Here we used the ASFV virulent isolate Ba71, adapted to grow in Vero cells (Ba71V), and the virulent strain E70 to demonstrate that entry and internalization of ASFV includes most of the features of macropinocytosis. By a combination of optical and electron microscopy, we show that the virus causes cytoplasm membrane perturbation, blebbing and ruffles. We have also found that internalization of the virions depends on actin reorganization, activity of Na +/H + exchangers, and signaling events typical of the macropinocytic mechanism of endocytosis. The entry of virus into cells appears to directly stimulate dextran uptake, actin polarization and EGFR, PI3K-Akt, Pak1 and Rac1 activation. Inhibition of these key regulators of macropinocytosis, as well as treatment with the drug EIPA, results in a considerable decrease in ASFV entry and infection. In conclusion, this study identifies for the first time the whole pathway for ASFV entry, including the key cellular factors required for the uptake of the virus and the cell signaling involved. © 2012 Sánchez et al.
URIhttp://hdl.handle.net/10261/111240
DOI10.1371/journal.ppat.1002754
Identifiersdoi: 10.1371/journal.ppat.1002754
issn: 1553-7366
Appears in Collections:(CBM) Artículos
Files in This Item:
File Description SizeFormat 
Y_Revilla_African_Swine.pdf7,9 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.