dc.contributor.author | Martínez-Bonet, Marta | |
dc.contributor.author | Palladino, Claudia | |
dc.contributor.author | Briz, Veronica | |
dc.contributor.author | Rudolph, Jochen M | |
dc.contributor.author | Fackler, Oliver T | |
dc.contributor.author | Relloso, Miguel | |
dc.contributor.author | Muñoz-Fernandez, Maria Angeles | |
dc.contributor.author | Madrid, Ricardo | |
dc.date.accessioned | 2021-04-23T09:22:22Z | |
dc.date.available | 2021-04-23T09:22:22Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | PLoS One. 2015 Dec 23;10(12):e0145239. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/12749 | |
dc.description.abstract | To find out new determinants required for Nef activity we performed a functional alanine scanning analysis along a discrete but highly conserved region at the core of HIV-1 Nef. We identified the GPG-motif, located at the 121-137 region of HIV-1 NL4.3 Nef, as a novel protein signature strictly required for the p56Lck dependent Nef-induced CD4-downregulation in T-cells. Since the Nef-GPG motif was dispensable for CD4-downregulation in HeLa-CD4 cells, Nef/AP-1 interaction and Nef-dependent effects on Tf-R trafficking, the observed effects on CD4 downregulation cannot be attributed to structure constraints or to alterations on general protein trafficking. Besides, we found that the GPG-motif was also required for Nef-dependent inhibition of ring actin re-organization upon TCR triggering and MHCI downregulation, suggesting that the GPG-motif could actively cooperate with the Nef PxxP motif for these HIV-1 Nef-related effects. Finally, we observed that the Nef-GPG motif was required for optimal infectivity of those viruses produced in T-cells. According to these findings, we propose the conserved GPG-motif in HIV-1 Nef as functional region required for HIV-1 infectivity and therefore with a potential interest for the interference of Nef activity during HIV-1 infection. | es_ES |
dc.description.sponsorship | This work was supported by the Ramon y Cajal research program (MICIIN-RYC-2005-002174; http://www.mineco.gob.es/portal/site/mineco/idi), Fondo de Investigación Sanitaria en España (FIS-PS09/01386; http://www.isciii.es/) to RM, and Comunidad de Madrid (S-2010/BMD-2332; http://www.madrimasd.org/) to MAM-F, and the Deutsche Forschungsgemeinschaft (TRR83, project 15 to OTF). MM-B, CP and VB hold a fellowship from the Fondo de Investigación Sanitaria en España (FIS, http://www.isciii.es/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Public Library of Science (PLOS) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Amino Acid Motifs | es_ES |
dc.subject.mesh | HIV-1 | es_ES |
dc.subject.mesh | HeLa Cells | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Protein Structure, Tertiary | es_ES |
dc.subject.mesh | Structure-Activity Relationship | es_ES |
dc.subject.mesh | T-Lymphocytes | es_ES |
dc.subject.mesh | nef Gene Products, Human Immunodeficiency Virus | es_ES |
dc.title | A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 26700863 | es_ES |
dc.format.volume | 10 | es_ES |
dc.format.number | 12 | es_ES |
dc.format.page | e0145239 | es_ES |
dc.identifier.doi | 10.1371/journal.pone.0145239 | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.contributor.funder | Deutsche Forschungsgemeinschaft (Alemania) | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1932-6203 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1371/journal.pone.0145239 | es_ES |
dc.identifier.journal | PloS one | es_ES |
dc.repisalud.centro | ISCIII | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/MICIIN-RYC-2005-002174 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/FIS-PS09/01386 | es_ES |
dc.rights.accessRights | open access | es_ES |