SAMHD1-Dependent and -Independent Functions of HIV-2/SIV Vpx Protein

Both human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) encode a unique set of accessory proteins that enhance viral replication in the host. Two similar accessory proteins, Vpx and Vpr, are encoded by HIV-2. In contrast, HIV-1 encodes Vpr but not Vpx. Recent studies have indicated that Vpx counteracts a particular host restriction factor, thereby facilitating reverse transcription in myeloid cells such as monocyte-derived macrophages and monocyte-derived dendritic cells. This mechanism of counteraction is similar to that of the accessory proteins Vif and Vpu which antagonize other host factors. In 2011, the protein SAMHD1 was identified as the restriction factor counteracted by Vpx. Studies have since revealed that SAMHD1 degrades deoxynucleoside triphosphates (dNTPs), which are components of viral genomic cDNA, in order to deprive viruses of dNTPs. Although interactions between SAMHD1 and Vpx continue to be a major research focus, Vpx has also been shown to have an apparent ability to enhance nuclear import of the viral genome in T lymphocytes. This review summarizes the current knowledge regarding SAMHD1-dependent and -independent functions of Vpx, and discusses possible reasons why HIV-2 encodes both Vpx and Vpr, unlike HIV-1.