| Literature DB >> 18329615 |
Hye-Sook Kwon1, Michael M Brent, Ruth Getachew, Prerana Jayakumar, Lin-Feng Chen, Martina Schnolzer, Michael W McBurney, Ronen Marmorstein, Warner C Greene, Melanie Ott.
Abstract
Symptoms of T cell hyperactivation shape the course and outcome of HIV-1 infection, but the mechanism(s) underlying this chronic immune activation are not well understood. We find that the viral transactivator Tat promotes hyperactivation of T cells by blocking the nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase SIRT1. Tat directly interacts with the deacetylase domain of SIRT1 and blocks the ability of SIRT1 to deacetylate lysine 310 in the p65 subunit of NF-kappaB. Because acetylated p65 is more active as a transcription factor, Tat hyperactivates the expression of NF-kappaB-responsive genes, a function lost in SIRT1-/- cells. These results support a model where the normal function of SIRT1 as a negative regulator of T cell activation is suppressed by Tat during HIV infection. These events likely contribute to the state of immune cell hyperactivation found in HIV-infected individuals.Entities:
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Year: 2008 PMID： 18329615 PMCID： PMC2680745 DOI： 10.1016/j.chom.2008.02.002
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023