SAMHD1: mechanisms of regulation and viral evasion

Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) is a restriction factor blocking replication of many viruses, including human imMunodeficiency virus (HIV). SAMHD1 was initially identified by homology with a murine GTPase induced by interferon gamma (IFN gamma) and known for its involvement in the Aicardi-Goutieres syndrome (AGS), a rare inflammatory disorder [1]. In 2011, the identification of SAMHD1 as the restriction factor inhibiting HIV-1 infection in macrophages and dendritic cells has been a major advance in the field of retrovirology [2, 3]. In this review, I will discuss recent advances on the mechanism of SAMHD1 restriction of HIV-1, the regulation of SAMHD1 by the cell cycle and by cytokines, and how viruses evolved to counteract SAMHD1 restriction.