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

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• 作者：Kevin O. Saunders ; Stephanie A. Freel ; R. Glenn Overman ; Coleen K. Cunningham ; Georgia D. Tomaras
• 关键词：Histone deacetylases ; CD8⁺ T-lymphocyte HIV-1 suppression ; Virus controllers
• 刊名：Virology
• 出版年：2010
• 出版时间：15 September 2010
• 年：2010
• 卷：405
• 期：1
• 页码：234-242
• 全文大小：788 K

文摘

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.