2024-03-28T19:35:56Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/48462023-09-29T10:01:08Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2060com_20.500.12105_2052com_20.500.12105_2152com_20.500.12105_2144col_20.500.12105_16938col_20.500.12105_2061col_20.500.12105_2153
Repisalud
author
Rodriguez‑Mora, Sara
author
Mateos, Elena
author
Moran, María
author
Martín, Miguel Ángel
author
Lopez, Juan Antonio
author
Calvo, Enrique
author
Terrón-Orellana, Maria Carmen
author
Luque, Daniel
author
Muriaux, Delphine
author
Alcamí, José
author
Coiras, Mayte
author
Lopez-Huertas, Maria Rosa
funder
Ministerio de Economía y Competitividad (España)
funder
Instituto de Salud Carlos III
funder
Ministerio de Sanidad, Servicios Sociales e Igualdad (España)
2017-09-04T16:33:50Z
2017-09-04T16:33:50Z
2015-09-16
Retrovirology. 2015 Sep 16;12:78.
http://hdl.handle.net/20.500.12105/4846
10.1186/s12977-015-0203-3
1742-4690
Retrovirology
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.
eng
HIV-1
Tat
Mitochondria
Cytoskeletal rearrangements
Aerobic glycolysis
mtDNA transcription
Intracellular expression of Tat alters mitochondrial functions in T cells: a potential mechanism to understand mitochondrial damage during HIV-1 replication
journal article
URL
https://repisalud.isciii.es/bitstream/20.500.12105/4846/1/IntracellularExpressionOfTat_2015
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MD5
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IntracellularExpressionOfTat_2015
URL
https://repisalud.isciii.es/bitstream/20.500.12105/4846/6/12977_2015_Article_203.pdf.txt
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12977_2015_Article_203.pdf.txt
URL
https://repisalud.isciii.es/bitstream/20.500.12105/4846/22/IntracellularExpressionOfTat_2015.txt
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MD5
bb3177a908bb8c47cb2399769dd94b52
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IntracellularExpressionOfTat_2015.txt