English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/11878
Compartir / Impacto:
Estadísticas
Add this article to your Mendeley library MendeleyBASE
Citado 66 veces en Web of Knowledge®  |  Pub MebCentral Ver citas en PubMed Central  |  Ver citas en Google académico
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Título

The host-dependent interaction of alpha-importins with influenza PB2 polymerase subunit is required for virus RNA replication

AutorResa-Infante, Patricia; Jorba, Núria; Zamarreño, Noelia; Fernández, Yolanda; Juárez, Silvia; Ortín, Juan
Fecha de publicación10-dic-2008
EditorPublic Library of Science
CitaciónPLoS ONE 3(12): e3904 (2008)
ResumenThe influenza virus polymerase is formed by the PB1, PB2 and PA subunits and is required for virus transcription and replication in the nucleus of infected cells. As PB2 is a relevant host-range determinant we expressed a TAP-tagged PB2 in human cells and isolated intracellular complexes. Alpha-importin was identified as a PB2-associated factor by proteomic analyses. To study the relevance of this interaction for virus replication we mutated the PB2 NLS and analysed the phenotype of mutant subunits, polymerase complexes and RNPs. While mutant PB2 proteins showed reduced nuclear accumulation, they formed polymerase complexes normally when co expressed with PB1 and PA. However, mutant RNPs generated with a viral CAT replicon showed up to hundred-fold reduced CAT accumulation. Rescue of nuclear localisation of mutant PB2 by insertion of an additional SV40 TAg-derived NLS did not revert the mutant phenotype of RNPs. Furthermore, determination of recombinant RNP accumulation in vivo indicated that PB2 NLS mutations drastically reduced virus RNA replication. These results indicate that, above and beyond its role in nuclear accumulation, PB2 interaction with α-importins is required for virus RNA replication. To ascertain whether PB2-α-importin binding could contribute to the adaptation of H5N1 avian viruses to man, their association in vivo was determined. Human alpha importin isoforms associated efficiently to PB2 protein of an H3N2 human virus but bound to diminished and variable extents to PB2 from H5N1 avian or human strains, suggesting that the function of alpha importin during RNA replication is important for the adaptation of avian viruses to the human host.
Descripción10 pages, 8 figures.-- PMID: 19066626 [PubMed].-- PMCID: PMC2588535.-- Supporting information (Suppl. figures S1-S2 & tables S1-S2) available at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003904
Versión del editorhttp://dx.doi.org/10.1371/journal.pone.0003904
URIhttp://hdl.handle.net/10261/11878
DOI10.1371/journal.pone.0003904
ISSN1932-6203
Aparece en las colecciones: (CNB) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
Resa_et_al_PLoS_ONE_3_12_2008.pdfMain text file1,27 MBAdobe PDFVista previa
Visualizar/Abrir
journal.pone.0003904.s001.tiffFig. S11,62 MBTIFFVista previa
Visualizar/Abrir
journal.pone.0003904.s002.tiffFig. S25,27 MBTIFFVista previa
Visualizar/Abrir
journal.pone.0003904.s003.docTable S127,5 kBMicrosoft WordVisualizar/Abrir
journal.pone.0003904.s004.docTable S2128,5 kBMicrosoft WordVisualizar/Abrir
Mostrar el registro completo
 



NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.