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dc.contributor.authorWidjaja, Ivy
dc.contributor.authorRigter, Alan
dc.contributor.authorJacobino, Shamir
dc.contributor.authorvan Kuppeveld, Frank J M
dc.contributor.authorLeenhouts, Kees
dc.contributor.authorPalomo-Sanz, Concepcion 
dc.contributor.authorMelero, Jose Antonio 
dc.contributor.authorLeusen, Jeanette H W
dc.contributor.authorHaijema, Bert Jan
dc.contributor.authorRottier, Peter J M
dc.contributor.authorde Haan, Cornelis A M
dc.date.accessioned2022-03-28T12:58:47Z
dc.date.available2022-03-28T12:58:47Z
dc.date.issued2015-06
dc.identifier.citationPLoS One. 2015 Jun 24;10(6):e0130829.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13868
dc.description.abstractThe respiratory syncytial virus (RSV) fusion protein F is considered an attractive vaccine candidate especially in its prefusion conformation. We studied whether recombinant soluble RSV F proteins could be stabilized in a prefusion-like conformation by mutation of heptad repeat B (HRB). The results show that soluble, trimeric, non-cleaved RSV F protein, produced by expression of the furin cleavage site-mutated F ectodomain extended with a GCN4 trimerization sequence, is efficiently recognized by pre- as well as postfusion-specific antibodies. In contrast, a similar F protein completely lacking HRB displayed high reactivity with prefusion-specific antibodies recognizing antigenic site Ø, but did not expose postfusion-specific antigenic site I, in agreement with this protein maintaining a prefusion-like conformation. These features were dependent on the presence of the GCN4 trimerization domain. Absence of cleavage also contributed to binding of prefusion-specific antibodies. Similar antibody reactivity profiles were observed when the prefusion form of F was stabilized by the introduction of cysteine pairs in HRB. To study whether the inability to form the 6HB was responsible for the prefusion-like antibody reactivity profile, alanine mutations were introduced in HRB. Although introduction of alanine residues in HRB inhibited the formation of the 6HB, the exposure of postfusion-specific antigenic site I was not prevented. In conclusion, proteins that are not able to form the 6HB, due to mutation of HRB, may still display postfusion-specific antigenic site I. Replacement of HRB by the GCN4 trimerization domain in a non-cleaved soluble F protein resulted, however, in a protein with prefusion-like characteristics, suggesting that this HRB-lacking protein may represent a potential prefusion F protein subunit vaccine candidate.es_ES
dc.description.sponsorshipThis study was funded in part by Mucosis B. V. No additional external funding was received for this study. We agree that the funder provided support in the form of salaries for authors [IW, AR, KL, BJH], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the "author contributions" section.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.meshAntibodies, Neutralizing es_ES
dc.subject.meshAntibodies, Viral es_ES
dc.subject.meshBinding Sites es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshEpithelial Cells es_ES
dc.subject.meshGene Expression es_ES
dc.subject.meshHEK293 Cells es_ES
dc.subject.meshHumans es_ES
dc.subject.meshModels, Moleculares_ES
dc.subject.meshProtein Binding es_ES
dc.subject.meshProtein Multimerization es_ES
dc.subject.meshProtein Structure, Tertiaryes_ES
dc.subject.meshRecombinant Proteins es_ES
dc.subject.meshRespiratory Mucosa es_ES
dc.subject.meshRespiratory Syncytial Virus, Humanes_ES
dc.subject.meshViral Fusion Proteins es_ES
dc.titleRecombinant Soluble Respiratory Syncytial Virus F Protein That Lacks Heptad Repeat B, Contains a GCN4 Trimerization Motif and Is Not Cleaved Displays Prefusion-Like Characteristicses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID26107504es_ES
dc.format.volume10es_ES
dc.format.number6es_ES
dc.format.pagee0130829es_ES
dc.identifier.doi10.1371/journal.pone.0130829es_ES
dc.contributor.funderMucosis B. V.es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1932-6203es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pone.0130829es_ES
dc.identifier.journalPloS Onees_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_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