Intracellular expression of Tat alters mitochondrial functions in T cells: a potential mechanism to understand mitochondrial damage during HIV-1 replication

Retrovirology. 2015 Sep 16;12:78. doi: 10.1186/s12977-015-0203-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / ultrastructure
  • CD4-Positive T-Lymphocytes / virology*
  • Cytoskeleton / pathology
  • Cytoskeleton / virology
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism
  • Exons
  • Glycolysis
  • HIV-1 / physiology*
  • Humans
  • Jurkat Cells
  • Leukocytes, Mononuclear
  • Mitochondria / genetics
  • Mitochondria / ultrastructure*
  • tat Gene Products, Human Immunodeficiency Virus / genetics*
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • DNA, Mitochondrial
  • tat Gene Products, Human Immunodeficiency Virus