Lentivirus Vpr and Vpx accessory proteins usurp the cullin4-DDB1 (DCAF1) E3 ubiquitin ligase.
Myeloid cells display a differential permissivity to primate lentivirus infection that is related to their ability to encode the Vpx and to a lesser extent the Vpr accessory proteins. Vpr is encoded by all primate lentiviruses, including HIV-1 and HIV-2, while its paralog, Vpx, is unique to HIV-2 and a subset of simian lentiviruses. Both proteins usurp the CRL4A (DCAF1) E3 ligase to fulfil their functions. Vpx induces the degradation of SAMHD1, a nucleotide triphosphohydrolase that blocks lentiviral reverse transcription in myeloid cells via depletion of the intracellular pool of dNTPs. Vpr engages CRL4A (DCAF1) to degrade a yet unknown factor(s), whose proteolysis induces a G2 cell-cycle arrest in dividing cells. Although the identification of the host protein(s) targeted for degradation by Vpr will be necessary to understand its actual function, the discovery of SAMHD1 has already shed light into a new mechanism of restriction that limits infection of myeloid cells by HIV-1.
Institut de Recherches Cliniques de Montréal, Montréal, Québec, Canada H2W 1R7.
Bizhan
B
Romani
Eric A
EA
Cohen
D002352:Carrier Proteins / Q000378:metabolism; D044842:Cullin Proteins / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity*; D015498:HIV-2 / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D059748:Proteolysis; D000076106:SAM Domain and HD Domain-Containing Protein 1; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
C114234:CUL4A protein, human; D002352:Carrier Proteins; D044842:Cullin Proteins; C074286:VPX protein, Human immunodeficiency virus 2; D054334:Viral Regulatory and Accessory Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; C514913:vpr protein, Human immunodeficiency virus 2; D044767:Ubiquitin-Protein Ligases; C530533:DCAF1 protein, human; D017346:Protein Serine-Threonine Kinases; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins