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

Cell Host Microbe. 2008 Mar 13;3(3):158-67. doi: 10.1016/j.chom.2008.02.002.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • HIV-1 / immunology*
  • Humans
  • Lymphocyte Activation / immunology*
  • Lysine / metabolism
  • Mice
  • Protein Binding
  • Protein Interaction Mapping
  • Sirtuin 1
  • Sirtuins / antagonists & inhibitors*
  • Sirtuins / deficiency
  • Sirtuins / immunology*
  • T-Lymphocytes / immunology*
  • Transcription Factor RelA / metabolism
  • tat Gene Products, Human Immunodeficiency Virus / immunology*
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*


  • Transcription Factor RelA
  • tat Gene Products, Human Immunodeficiency Virus
  • SIRT1 protein, human
  • Sirtuin 1
  • Sirtuins
  • Lysine