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dc.contributor.authorRodriguez Martinez, Javier M 
dc.contributor.authorChichón, Francisco J
dc.contributor.authorMartin-Forero, Esther 
dc.contributor.authorGonzalez-Camacho, Fernando 
dc.contributor.authorCarrascosa, José L
dc.contributor.authorCastón, José R
dc.contributor.authorLuque, Daniel 
dc.date.accessioned2018-12-26T14:45:20Z
dc.date.available2018-12-26T14:45:20Z
dc.date.issued2014-05-29
dc.identifier.citationPLoS Pathog. 2014 May 29;10(5):e1004157es_ES
dc.identifier.issn1553-7374es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6945
dc.description.abstractThe infectivity of rotavirus, the main causative agent of childhood diarrhea, is dependent on activation of the extracellular viral particles by trypsin-like proteases in the host intestinal lumen. This step entails proteolytic cleavage of the VP4 spike protein into its mature products, VP8* and VP5*. Previous cryo-electron microscopy (cryo-EM) analysis of trypsin-activated particles showed well-resolved spikes, although no density was identified for the spikes in uncleaved particles; these data suggested that trypsin activation triggers important conformational changes that give rise to the rigid, entry-competent spike. The nature of these structural changes is not well understood, due to lack of data relative to the uncleaved spike structure. Here we used cryo-EM and cryo-electron tomography (cryo-ET) to characterize the structure of the uncleaved virion in two model rotavirus strains. Cryo-EM three-dimensional reconstruction of uncleaved virions showed spikes with a structure compatible with the atomic model of the cleaved spike, and indistinguishable from that of digested particles. Cryo-ET and subvolume average, combined with classification methods, resolved the presence of non-icosahedral structures, providing a model for the complete structure of the uncleaved spike. Despite the similar rigid structure observed for uncleaved and cleaved particles, trypsin activation is necessary for successful infection. These observations suggest that the spike precursor protein must be proteolytically processed, not to achieve a rigid conformation, but to allow the conformational changes that drive virus entry.es_ES
dc.description.sponsorshipThis work was supported by grants from the Funds for Health Research (FIS) from the Spanish Ministry of Economy and Competitivity (AES/FIS, PI08/0688 to JMR and AES/FIS, PI10/00895 to DL), and BFU2011-29038 (to JLC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Science (PLOS) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshAnimals es_ES
dc.subject.meshCapsid es_ES
dc.subject.meshCells, Cultured es_ES
dc.subject.meshDiarrhea es_ES
dc.subject.meshHaplorhini es_ES
dc.subject.meshRotavirus es_ES
dc.subject.meshTrypsin es_ES
dc.subject.meshVirion es_ES
dc.subject.meshVirus Attachment es_ES
dc.subject.meshVirus Internalization es_ES
dc.titleNew insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavagees_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID24873828es_ES
dc.format.volume10es_ES
dc.format.number5es_ES
dc.format.pagee1004157es_ES
dc.identifier.doi10.1371/journal.ppat.1004157es_ES
dc.contributor.funderInstituto de Salud Carlos III 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1553-7374es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.ppat.1004157es_ES
dc.identifier.journalPLoS pathogenses_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI08/0688es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI10/00895es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU2011-29038es_ES
dc.rights.accessRightsopen accesses_ES


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Atribución 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución 4.0 Internacional