Sirtuin-1 and HIV-1: an overview

Sirtuins are a family of NAD+-dependent protein deacetylases, which regulate cellsurvival and energy metabolism, inflammation and cancer. Recent studies haveshown that sirtuin-1 (SIRT1) modulates Human Immunodeficiency Virus (HIV)-1transcription. The HIV-1 Tat protein is a substrate for the deacetylase activity of SIRT1; SIRT1 recycles Tat to its unacetylated form, catalyzing a fundamentalstep to start new cycles of viral transcription. Moreover, Tat has been reported to promote T-cell hyperactivation by suppressing SIRT1 activity. In fact, Tatblocks the ability of SIRT1 to deacetylate lysine 310 in the p65 subunit ofnuclear factor- κB (NF- κB) by interacting with the deacetylase domain of SIRT1. This mechanism leads therefore to the hyperactivation of NF- κB proinflammatorypathway and may likely contribute to the chronic immune activation state ofHIV-infected individuals. In the present review we first briefly describe thebiological functions of sirtuins, then we delineate the interplay between SIRT1and HIV-1 and discuss the potential role of SIRT1 as a pharmacological target of HIV-1 replication.