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Data suggest that a critical role of vpx in vivo/in vitro is to promote degradation of SAMHD1 (SAM domain/HD domain protein 1) in memory CD4+ T-lymphocytes, thereby generating high levels of plasma viremia and induction of immunodeficiency.
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Vpr and Vpx share a highly similar DCAF1-binding motif, they interact with a different set of residues in DCAF1.
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SIV vpx is essential for macrophage infection but not for development of simian AIDS.
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Inhibition of deoxynucleotide hydrolysis by promoting SAMHD1 degradation is not the only mechanism by which Vpx rescues HIV-1 in mature monocyte-derived dendritic cells from the antiviral state.
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direct down-modulation of Vpx catalytic activity, mediated by the same binding event that leads to SAMHD1 recruitment to the E3 ubiquitin ligase for proteasome-dependent degradation
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The authors demonstrate that the Wx4Phix2Phix3APhixH motif in SIVmac Vpx is required for both the Vpx-DCAF1 interaction and/or Vpx-mediated degradation of SAMHD1.
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However, all the vpx mutant viruses were defective for replication in both human and pigtail monocyte-derived macrophages.
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Vpx induces proteasomal degradation of SAMHD1
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Vpx relieves the inhibition of lentivirus infection in macrophages by loading SAMHD1 onto the CRL4(DCAF1) E3 ubiquitin ligase, leading to highly efficient proteasome-dependent degradation of the protein
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This review describes the main functions ascribed to Vpr and Vpx in the context of both viral replication and modulation of host cell biology
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A single-point mutation in Vpx (H82A) abrogated binding to APOBEC3A and single-round infection of monocytes by HIV-1.
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Vpx is essential to overcome a block of early infection steps in primary monocytes
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host cell MAPK signal transduction pathway regulates an early step in SIV infection
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MacrophageS harbor a potent antiviral restriction; primate lentiviruses have evolved Vpx to counteract this restriction.
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when transferred in the context of a replication-competent viral clone, Vpx was required for replication in dendritic cells