dc.contributor.author | Lopez-Huertas, Maria Rosa | |
dc.contributor.author | Mateos, Elena | |
dc.contributor.author | Sanchez-Del Cojo, Maria | |
dc.contributor.author | Gómez-Esquer, Francisco | |
dc.contributor.author | Díaz-Gil, Gema | |
dc.contributor.author | Rodriguez‑Mora, Sara | |
dc.contributor.author | Lopez, Juan Antonio | |
dc.contributor.author | Calvo, Enrique | |
dc.contributor.author | López-Campos, Guillermo | |
dc.contributor.author | Alcamí, José | |
dc.contributor.author | Coiras, Mayte | |
dc.date.accessioned | 2018-11-30T13:50:35Z | |
dc.date.available | 2018-11-30T13:50:35Z | |
dc.date.issued | 2013-03-15 | |
dc.identifier.citation | J Biol Chem. 2013; 288(11):7626-44 | es_ES |
dc.identifier.issn | 0021-9258 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/6749 | |
dc.description.abstract | HIV-1 replication is efficiently controlled by the regulator protein Tat (101 amino acids) and codified by two exons, although the first exon (1-72 amino acids) is sufficient for this process. Tat can be released to the extracellular medium, acting as a soluble pro-apoptotic factor in neighboring cells. However, HIV-1-infected CD4(+) T lymphocytes show a higher resistance to apoptosis. We observed that the intracellular expression of Tat delayed FasL-mediated apoptosis in both peripheral blood lymphocytes and Jurkat cells, as it is an essential pathway to control T cell homeostasis during immune activation. Jurkat-Tat cells showed impairment in the activation of caspase-8, deficient release of mitochondrial cytochrome c, and delayed activation of both caspase-9 and -3. This protection was due to a profound deregulation of proteins that stabilized the mitochondrial membrane integrity, such as heat shock proteins, prohibitin, or nucleophosmin, as well as to the up-regulation of NF-κB-dependent anti-apoptotic proteins, such as BCL2, c-FLIPS, XIAP, and C-IAP2. These effects were observed in Jurkat expressing full-length Tat (Jurkat-Tat101) but not in Jurkat expressing the first exon of Tat (Jurkat-Tat72), proving that the second exon, and particularly the NF-κB-related motif ESKKKVE, was necessary for Tat-mediated protection against FasL apoptosis. Accordingly, the protection exerted by Tat was independent of its function as a regulator of both viral transcription and elongation. Moreover, these data proved that HIV-1 could have developed strategies to delay FasL-mediated apoptosis in infected CD4(+) T lymphocytes through the expression of Tat, thus favoring the persistent replication of HIV-1 in infected T cells. | es_ES |
dc.description.sponsorship | This work was supported in part by Fundación para la Investigación y la Prevención del Sida en España Grant 360924/10, Spanish Ministry of Economy and Competitiveness Grant SAF2010-18388), Spanish Ministry of Health Grant EC11-285, AIDS Network Instituto del Salud Carlos III-Redes Temáticas de Investigación Cooperativa Grant RD06/0006, Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness Grant Fondo de Investigaciones Sanitarias PI080752, and the Network of Excellence EUROPRISE. | es_ES |
dc.language.iso | eng | es_ES |
dc.type.hasVersion | AM | es_ES |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | CD4-Positive T-Lymphocytes | es_ES |
dc.subject.mesh | Caspase 3 | es_ES |
dc.subject.mesh | Caspase 8 | es_ES |
dc.subject.mesh | Caspase 9 | es_ES |
dc.subject.mesh | Cytochromes c | es_ES |
dc.subject.mesh | Exons | es_ES |
dc.subject.mesh | HIV-1 | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Jurkat Cells | es_ES |
dc.subject.mesh | Mitochondria | es_ES |
dc.subject.mesh | Mutagenesis, Site-Directed | es_ES |
dc.subject.mesh | NF-kappa B | es_ES |
dc.subject.mesh | Oligonucleotide Array Sequence Analysis | es_ES |
dc.subject.mesh | Proteome | es_ES |
dc.subject.mesh | Proteomics | es_ES |
dc.subject.mesh | Transfection | es_ES |
dc.subject.mesh | fas Receptor | es_ES |
dc.subject.mesh | tat Gene Products, Human Immunodeficiency Virus | es_ES |
dc.subject.mesh | Apoptosis | es_ES |
dc.subject.mesh | Gene Expression Regulation | es_ES |
dc.title | The presence of HIV-1 Tat protein second exon delays fas protein-mediated apoptosis in CD4+ T lymphocytes: a potential mechanism for persistent viral production | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution 4.0 International | * |
dc.identifier.pubmedID | 23364796 | es_ES |
dc.format.volume | 288 | es_ES |
dc.format.number | 11 | es_ES |
dc.format.page | 7626-44 | es_ES |
dc.identifier.doi | 10.1074/jbc.M112.408294 | es_ES |
dc.contributor.funder | Fundación para la Investigación y la Prevención del Sida en España | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | RETICS-Sida (RIS-ISCIII) (España) | |
dc.contributor.funder | Ministerio de Sanidad y Política Social (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.description.peerreviewed | Sí | es_ES |
dc.relation.publisherversion | https://doi.org/10.1074/jbc.M112.408294 | es_ES |
dc.identifier.journal | The Journal of biological chemistry | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Proteómica / Metabolómica | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2010-18388 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/EC11-285 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD06/0006 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI080752 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/FI09/00347 | es_ES |
dc.rights.accessRights | open access | es_ES |