Title |
Intracellular expression of Tat alters mitochondrial functions in T cells: a potential mechanism to understand mitochondrial damage during HIV-1 replication
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Published in |
Retrovirology, September 2015
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DOI | 10.1186/s12977-015-0203-3 |
Pubmed ID | |
Authors |
Sara Rodríguez-Mora, Elena Mateos, María Moran, Miguel Ángel Martín, Juan Antonio López, Enrique Calvo, María Carmen Terrón, Daniel Luque, Delphine Muriaux, José Alcamí, Mayte Coiras, María Rosa López-Huertas |
Abstract |
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. 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Portugal | 1 | 50% |
United Kingdom | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Spain | 1 | 2% |
United States | 1 | 2% |
India | 1 | 2% |
Unknown | 62 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 13 | 20% |
Student > Ph. D. Student | 10 | 15% |
Student > Bachelor | 8 | 12% |
Student > Master | 8 | 12% |
Student > Doctoral Student | 5 | 8% |
Other | 8 | 12% |
Unknown | 13 | 20% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 12 | 18% |
Immunology and Microbiology | 10 | 15% |
Agricultural and Biological Sciences | 9 | 14% |
Medicine and Dentistry | 8 | 12% |
Nursing and Health Professions | 3 | 5% |
Other | 8 | 12% |
Unknown | 15 | 23% |