Epigenetic regulation of CD8(+) T-lymphocyte mediated suppression of HIV-1 replication.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Saunders, KO; Freel, SA; Overman, RG; Cunningham, CK; Tomaras, GD

Published Date

  • September 15, 2010

Published In

Volume / Issue

  • 405 / 1

Start / End Page

  • 234 - 242

PubMed ID

  • 20594570

Pubmed Central ID

  • 20594570

Electronic International Standard Serial Number (EISSN)

  • 1096-0341

Digital Object Identifier (DOI)

  • 10.1016/j.virol.2010.06.001

Language

  • eng

Conference Location

  • United States