Determinants for degradation of SAMHD1, Mus81 and induction of G2 arrest in HIV-1 Vpr and SIVagm Vpr

highlights•SIVagm Vpr C-t can induce G2 arrest in human cells when in the context of HIV-1 Vpr.•The N-terminal domain of SIVagm Vpr is required for agmSAMHD1 degradation.•Degradation of Mus81 and induction of G2 arrest by Vpr are independent functions.

Vpr and Vpx are a group of highly related accessory proteins from primate lentiviruses. Despite the high degree of amino acid homology within this group, these proteins can be highly divergent in their functions. In this work, we constructed chimeric and mutant proteins between HIV-1 and SIVagm Vpr in order to better understand the structure-function relationships. We tested these constructs for their abilities to induce G2 arrest in human cells and to degrade agmSAMHD1 and Mus81. We found that the C-terminus of HIV-1 Vpr, when transferred onto SIVagm Vpr, provides the latter with the de novo ability to induce G2 arrest in human cells. We confirmed that HIV-1 Vpr induces degradation of Mus81 although, surprisingly, degradation is independent and genetically separable from Vpr׳s ability to induce G2 arrest.