Sofia Banchenko, Ferdinand Krupp, Christine Gotthold, Jörg Bürger, Andrea Graziadei, Francis J O'Reilly, Ludwig Sinn, Olga Ruda, Juri Rappsilber, Christian M T Spahn, Thorsten Mielke, Ian A Taylor, David Schwefel
Viruses have evolved means to manipulate the host's ubiquitin-proteasome system, in order to down-regulate antiviral host factors. The Vpx/Vpr family of lentiviral accessory proteins usurp the substrate receptor DCAF1 of host Cullin4-RING ligases (CRL4), a family of modular ubiquitin ligases involved in DNA replication, DNA repair and cell cycle regulation. CRL4DCAF1 specificity modulation by Vpx and Vpr from certain simian immunodeficiency viruses (SIV) leads to recruitment, poly-ubiquitylation and subsequent proteasomal degradation of the host restriction factor SAMHD1, resulting in enhanced virus replication in differentiated cells...
August 2021: PLoS Pathogens