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dc.contributor.author | Rossey, Iebe | |
dc.contributor.author | Gilman, Morgan S A | |
dc.contributor.author | Kabeche, Stephanie C | |
dc.contributor.author | Sedeyn, Koen | |
dc.contributor.author | Wrapp, Daniel | |
dc.contributor.author | Kanekiyo, Masaru | |
dc.contributor.author | Chen, Man | |
dc.contributor.author | Spitaels, Jan | |
dc.contributor.author | Graham, Barney S | |
dc.contributor.author | Schepens, Bert | |
dc.contributor.author | McLellan, Jason S | |
dc.contributor.author | Saelens, Xavier | |
dc.contributor.author | Mas-Lloret, Vicente | |
dc.contributor.author | Melero, Jose Antonio | |
dc.date.accessioned | 2020-06-16T07:34:00Z | |
dc.date.available | 2020-06-16T07:34:00Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Nat Commun . 2017 Feb 13;8:14158. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/10416 | |
dc.description.abstract | Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV. | es_ES |
dc.description.sponsorship | We thank Amanda Gonçalves and Eef Parthoens from VIB Bio Imaging Core, Liesbeth Vande Ginste, Lien Van Hoecke, Soraya Van Cauwenberghe and Emilie Shipman for excellent technical assistance and Dr Florencia Linéro for providing the control VHH. This study was supported by IWT-Vlaanderen (Ph.D. student fellowship to I.R.), National Institute of General Medical Sciences of the National Institutes of Health award T32GM008704 (M.S.A.G.) and P20GM113132 (J.S.M.), FWO-Vlaanderen (Postdoctoral fellowship to B.S.), Ghent University Special Research Grant BOF12/GOA/014, Interuniversity Attraction Poles programme (IAP7, BELVIR), VIB and Mineco (Spain) Grant SAF2015-67033-R (J.A.M.). Results shown in this report are derived in part from work performed at Argonne National Laboratory, Structural Biology Center at the Advanced Photon Source. Argonne is operated by UChicago Argonne, LLC, for the U.S. Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357. Data in this report were also obtained at GM/CA@APS, which has been funded in whole or in part with Federal funds from the National Cancer Institute (ACB-12002) and the National Institute of General Medical Sciences (AGM-12006). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Antibodies, Neutralizing | es_ES |
dc.subject.mesh | Camelids, New World | es_ES |
dc.subject.mesh | Chlorocebus aethiops | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Monocytes | es_ES |
dc.subject.mesh | Protein Binding | es_ES |
dc.subject.mesh | Respiratory Syncytial Virus Infections | es_ES |
dc.subject.mesh | Respiratory Syncytial Virus, Human | es_ES |
dc.subject.mesh | Single-Domain Antibodies | es_ES |
dc.subject.mesh | T-Lymphocytes | es_ES |
dc.subject.mesh | Vero Cells | es_ES |
dc.subject.mesh | Viral Fusion Proteins | es_ES |
dc.subject.mesh | Virus Replication | es_ES |
dc.title | Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 28194013 | es_ES |
dc.format.volume | 8 | es_ES |
dc.format.page | 14158 | es_ES |
dc.identifier.doi | 10.1038/ncomms14158 | es_ES |
dc.contributor.funder | National Institutes of Health (Estados Unidos) | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | NIH - National Cancer Institute (NCI) (Estados Unidos) | |
dc.contributor.funder | NIH - National Institute of General Medical Sciences (NIGMS) (Estados Unidos) | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2041-1723 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1038/ncomms14158 | es_ES |
dc.identifier.journal | Nature communications | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/T32GM008704 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/BOF12/GOA/014 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/SAF2015-67033-R | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/DE-AC02-06CH11357 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/ACB-12002 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/AGM-12006 | es_ES |
dc.rights.accessRights | open access | es_ES |