title: Intracellular expression of Tat alters mitochondrial functions in T cells: a potential mechanism to understand mitochondrial damage during HIV-1 replication.
abstract: BACKGROUND
  HIV-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.
authors.affiliation: Unidad de Inmunopatología del SIDA, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. srmora@isciii.es.
authors.forename: Sara
authors.initials: S
authors.lastname: Rodríguez-Mora
authors.affiliation: Unidad de Inmunopatología del SIDA, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. emateo@isciii.es.
authors.forename: Elena
authors.initials: E
authors.lastname: Mateos
authors.affiliation: Laboratorio de Enfermedades Raras: mitocondriales y neuromusculares, Instituto de Investigación Hospital 12 de Octubre, "i + 12", Madrid, Spain. mmoran@h12o.es.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) U723, Madrid, Spain. mmoran@h12o.es.
authors.forename: María
authors.initials: M
authors.lastname: Moran
authors.affiliation: Laboratorio de Enfermedades Raras: mitocondriales y neuromusculares, Instituto de Investigación Hospital 12 de Octubre, "i + 12", Madrid, Spain. mamcasanueva@h12o.es.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) U723, Madrid, Spain. mamcasanueva@h12o.es.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Martín
authors.affiliation: Unidad de Proteómica, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. jalopez@cnic.es.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: López
authors.affiliation: Unidad de Proteómica, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. ecalvo@cnic.es.
authors.forename: Enrique
authors.initials: E
authors.lastname: Calvo
authors.affiliation: Unidad de Microscopía Electrónica y Confocal, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. mcterron@isciii.es.
authors.forename: María Carmen
authors.initials: MC
authors.lastname: Terrón
authors.affiliation: Unidad de Microscopía Electrónica y Confocal, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. dluque@isciii.es.
authors.forename: Daniel
authors.initials: D
authors.lastname: Luque
authors.affiliation: Unité de Virologie Humaine - INSERM U758/École Normale Supérieure, Lyon, France. delphine.muriaux@cpbs.cnrs.fr.|Laboratoire de Domaines Membranaires et Assemblage Viral, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé, Montpellier, France. delphine.muriaux@cpbs.cnrs.fr.
authors.forename: Delphine
authors.initials: D
authors.lastname: Muriaux
authors.affiliation: Unidad de Inmunopatología del SIDA, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. ppalcami@isciii.es.
authors.forename: José
authors.initials: J
authors.lastname: Alcamí
authors.affiliation: Unidad de Inmunopatología del SIDA, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. mcoiras@isciii.es.
authors.forename: Mayte
authors.initials: M
authors.lastname: Coiras
authors.affiliation: Unidad de Inmunopatología del SIDA, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. mrlhuertas@isciii.es.|Unité de Virologie Humaine - INSERM U758/École Normale Supérieure, Lyon, France. mrlhuertas@isciii.es.
authors.forename: María Rosa
authors.initials: MR
authors.lastname: López-Huertas
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology*; D003599:Cytoskeleton / Q000473:pathology / Q000821:virology; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D006019:Glycolysis; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear; D008928:Mitochondria / Q000235:genetics / Q000648:ultrastructure*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D054322:tat Gene Products, Human Immunodeficiency Virus