Abstract:
: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.
journal_name
Virologyjournal_title
Virologyauthors
Saunders KO,Freel SA,Overman RG,Cunningham CK,Tomaras GDdoi
10.1016/j.virol.2010.06.001subject
Has Abstractpub_date
2010-09-15 00:00:00pages
234-42issue
1eissn
0042-6822issn
1096-0341pii
S0042-6822(10)00381-8journal_volume
405pub_type
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