Unknown

Dataset Information

0

Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1 deacetylase and induces T cell hyperactivation.


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.

PROVIDER: S-EPMC2680745 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

2008-01-01 | S-EPMC2292827 | BioStudies
| S-EPMC2532814 | BioStudies
| S-EPMC2628607 | BioStudies
| S-EPMC7473906 | BioStudies
2007-01-01 | S-EPMC2049082 | BioStudies
2012-01-01 | S-EPMC3333881 | BioStudies
| S-EPMC5133964 | BioStudies
| S-EPMC5841350 | BioStudies
2006-01-01 | S-EPMC1356344 | BioStudies
| S-EPMC2430207 | BioStudies