Abstract
Background SAMHD1, a dGTP-regulated deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase, down-regulates dNTP pools in terminally differentiated and quiescent cells, thereby inhibiting HIV-1 infection at the reverse transcription step. HIV-2 and SIV counteract this restriction via a virion-associated virulence accessory factor, Vpx (Vpr in some SIVs), which loads SAMHD1 onto CRL4-DCAF1 E3 ubiquitin ligase for poly-ubiquitination, programming it for proteasome-dependent degradation. However, the detailed molecular mechanisms of SAMHD1 recruitment to the E3 ligase have not been defined. Further, whether divergent, orthologous Vpr/Vpx proteins, encoded by distinct HIV/ SIV strains, bind SAMHD1 in a similar manner, at a molecular level, is not known.
Highlights
SAMHD1, a dGTP-regulated deoxyribonucleoside triphosphate triphosphohydrolase, down-regulates dNTP pools in terminally differentiated and quiescent cells, thereby inhibiting HIV-1 infection at the reverse transcription step
HIV-2 and SIV counteract this restriction via a virion-associated virulence accessory factor, Vpx (Vpr in some SIVs), which loads SAMHD1 onto CRL4-DCAF1 E3 ubiquitin ligase for poly-ubiquitination, programming it for proteasome-dependent degradation
Materials and methods We applied systematic biochemical and bioanalytical approaches to investigate molecular mechanisms of SAMHD1 recruitment to CRL4-DCAF1 E3 ubiquitin ligase in complex with Vpr/Vpx
Summary
SAMHD1, a dGTP-regulated deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase, down-regulates dNTP pools in terminally differentiated and quiescent cells, thereby inhibiting HIV-1 infection at the reverse transcription step. Molecular mechanisms of the interplay between Vpx and SAMHD1 From Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts Cambridge, UK.
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