Structural basis of clade-specific engagement of SAMHD1 (sterile α motif and histidine/aspartate-containing protein 1) restriction factors by lentiviral viral protein X (Vpx) virulence factors

Abstract

Background: Lentiviral Vpx binding to primate SAMHD1 is under positive selection. Results: Different Vpx protein variants interact with the N-terminal domain or the C-terminal tail of SAMHD1 in ubiquitinligase-substrate receptor complexes in a unique fashion. Conclusion: Vpx antagonizes SAMHD1 by recruiting it via two separate regions for proteasomal degradation. Significance: Our findings shed light on how lentivirus virulence factors intersect with host innate immunity.