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dc.contributor.authorRodriguez‑Mora, Sara 
dc.contributor.authorMateos, Elena 
dc.contributor.authorMoran, María
dc.contributor.authorMartín, Miguel Ángel
dc.contributor.authorLopez, Juan Antonio 
dc.contributor.authorCalvo, Enrique 
dc.contributor.authorTerrón, María Carmen
dc.contributor.authorLuque, Daniel 
dc.contributor.authorMuriaux, Delphine
dc.contributor.authorAlcamí, José 
dc.contributor.authorCoiras, Mayte 
dc.contributor.authorLopez-Huertas, Maria Rosa
dc.identifier.citationRetrovirology. 2015 Sep 16;12:78.
dc.description.abstractHIV-1 replication results in mitochondrial damage that is enhanced during antiretroviral therapy (ART). The onset of HIV-1 replication is regulated by viral protein Tat, a 101-residue protein codified by two exons that elongates viral transcripts. Although the first exon of Tat (aa 1–72) forms itself an active protein, the presence of the second exon (aa 73–101) results in a more competent transcriptional protein with additional functions. Results: Mitochondrial overall functions were analyzed in Jurkat cells stably expressing full-length Tat (Tat101) or one-exon Tat (Tat72). Representative results were confirmed in PBLs transiently expressing Tat101 and in HIV-infected Jurkat cells. The intracellular expression of Tat101 induced the deregulation of metabolism and cytoskeletal proteins which remodeled the function and distribution of mitochondria. Tat101 reduced the transcription of the mtDNA, resulting in low ATP production. The total amount of mitochondria increased likely to counteract their functional impairment. These effects were enhanced when Tat second exon was expressed. Conclusions: Intracellular Tat altered mtDNA transcription, mitochondrial content and distribution in CD4+ T cells. The importance of Tat second exon in non-transcriptional functions was confirmed. Tat101 may be responsible for mitochondrial dysfunctions found in HIV-1 infected patients.
dc.description.sponsorshipWe greatly appreciate the secretarial assistance of Mrs Olga Palao. This work was supported by FIPSE (360924/10), Spanish Ministry of Economy and Competitiveness (SAF2010-18388), Spanish Ministry of Health (EC11- 285), AIDS Network ISCIII-RETIC (RD12/0017/0015), Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness (FIS PI12/00506). The work of Sara Rodríguez-Mora is supported by a fellowship of Sara Borrell from Spanish Ministry of Economy and Competitiveness (2013). The work of María Rosa López-Huertas is supported by a fellowship of the European Union Programme Health 2009 (CHAARM).
dc.publisherBioMed Central (BMC) 
dc.subjectCytoskeletal rearrangements
dc.subjectAerobic glycolysis
dc.subjectmtDNA transcription
dc.titleIntracellular expression of Tat alters mitochondrial functions in T cells: a potential mechanism to understand mitochondrial damage during HIV-1 replication
dc.typejournal article
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderMinisterio de Sanidad, Servicios Sociales e Igualdad (España) 
dc.repisalud.centroISCIII::Centro Nacional de Microbiología::Área de Patología Molecular::Unidad de Inmunopatología del Sida
dc.repisalud.centroISCIII::Centro Nacional de Microbiología::Unidades Comunes Científico-Técnicas (UCCT)::Unidad de Microscopía Electrónica y Confocal
dc.repisalud.orgCNICCNIC::Unidades técnicas::Proteómica / Metabolómica
dc.rights.accessRightsopen accesses_ES

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Atribución 4.0 Internacional
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