Determinants of lentiviral Vpx-CRL4 E3 ligase-mediated SAMHD1 degradation in the substrate adaptor protein DCAF1
Determinants of lentiviral Vpx-CRL4 E3 ligase-mediated SAMHD1 degradation in the substrate adaptor protein DCAF1
复制标题
底物接头蛋白DCAF1中慢病毒Vpx-CRL4 E3连接酶介导的SAMHD1降解的决定因素
DOI：
10.1016/j.bbrc.2019.04.085
复制
发表时间：
2019-06-11
影响因子：
3.1
通讯作者：
Wei, Wei
中科院分区：
文献类型：
--
作者：
Guo, Haoran;Zhang, Nannan;Wei, Wei
The lentiviral accessory protein Vpx enhances viral replication in macrophages, dendritic cells and resting CD4(+) T cells by utilizing the host CRL4-DCAF1 E3 ligase to trigger the degradation of the intrinsic antiviral factor SAMHD1. Distinct from the species-specific recognition of either the N- or C-terminus of SAMHD1 by Vpx proteins of different HIV-2 and SIV lineages, Vpx recruits SAMHD1 onto the same CRL4-DCAF1 complex. However, the determinants in DCAF1 that are required for Vpx-mediated SAMHD1 degradation have not been well characterized. Here, we demonstrate that the viral protein Vpx is resistant to suppression by a cellular inhibitor of the CRL4-DCAF1 E3 ligase, Merlin/NF2, through targeting a separate binding region in DCAF1. The Merlin binding-deficient DCAF1 truncation mutant (1-1417) is sufficient for Vpx-CRL4-DCAF1 E3 ligase assembly and SAMHDI degradation. We found that the carboxyl-terminus ED-rich region (1312-1417) of DCAF1 is required for the nuclear localization of DCAF1 and for the Vpx-DCAF1 interaction. We identified the DCAF1 (1-1311) truncation mutant as a dominant negative mutant of wild-type DCAF1 that inhibits Vpx-mediated SAMHDI degradation. These results suggest a unique strategy by which Vpx exploits DCAF1 to counteract this host restriction factor. (C) 2019 Elsevier Inc. All rights reserved.
