Epigenetic regulation of CD8(+) T-lymphocyte mediated suppression of HIV-1 replication.
CD8(+) T-lymphocytes from HIV-1 infected individuals express unidentified factors that suppress viral replication by inhibiting HIV-1 gene expression. We examined the role of epigenetics in modulating the HIV-1 suppressive factors expressed by primary CD8(+) T cells from subjects naturally controlling virus replication. HIV-1 suppression by CD8(+) T-lymphocytes was reversed up to 40% by the addition of a histone deacetylase (HDAC) inhibitor. Noncytolytic suppression was not dependent on epigenetic changes within the target cells, as HDAC1 within the target cell was dispensable, and HIV-1 LTR histone acetylation remained unchanged in the presence of CD8(+) T-lymphocytes. Histone deacetylation within CD8(+) T-lymphocytes was necessary for potent HIV-1 suppression. Blocking HDACs impairs the ability of CD8(+) T-lymphocytes to repress HIV-1 transcription, demonstrating that expression of a portion of the suppressive factors is regulated by epigenetics. These data provide a way to focus the search for the suppressive factors and to potentially modulate their expression.
Saunders
Kevin O
KO
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, 27710, USA.
Freel
Stephanie A
SA
Overman
R Glenn
RG
Cunningham
Coleen K
CK
Tomaras
Georgia D
GD
D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D056284:Histone Deacetylase 1; D006657:Histones; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology; D034622:RNA Interference; D014779:Virus Replication / Q000502:physiology*
D006657:Histones; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1