2026-06-14T03:40:11Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/166142025-06-09T08:53:24Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_19604col_20.500.12105_19609col_20.500.12105_19605
Repisalud author Lopez-Huertas, Maria Rosa author Mateos, Elena author Sanchez-Del Cojo, Maria author Gómez-Esquer, Francisco author Díaz-Gil, Gema author Rodríguez-Mora, Sara author Lopez, Juan Antonio author Calvo, Enrique author Lopez-Campos, Guillermo author Alcamí, José author Coiras, Mayte funder Fundación para la Investigación y la Prevención del Sida en España funder Ministerio de Economía y Competitividad (España) funder RETICS-Sida (RIS-ISCIII) (España) funder Ministerio de Sanidad y Política Social (España) funder Instituto de Salud Carlos III funder Unión Europea 2023-10-26T11:15:51Z 2023-10-26T11:15:51Z 2013-03-15 J Biol Chem. 2013 Mar 15;288(11):7626-7644. 10.1074/jbc.M112.408294 1083-351X The Journal of biological chemistry 23364796 http://hdl.handle.net/20.500.12105/16614 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. eng 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 research article 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 URL https://repisalud.isciii.es/bitstreams/00c51c5c-6aed-41c9-a28d-d14df315b9d6/download File MD5 3955b03dcfc2a79518ddcf17b5108472 4420828 application/pdf PresenceHIV-1_TatProtein_2013.pdf URL https://repisalud.isciii.es/bitstreams/064a9709-672d-4111-8f05-e44c7e5af71a/download File MD5 d50f0fdbc43aec09b68e67c59fb0caba 99770 text/plain PresenceHIV-1_TatProtein_2013.pdf.txt