title: A first-in-class NAE inhibitor, MLN4924, blocks lentiviral infection in myeloid cells by disrupting neddylation-dependent Vpx-mediated SAMHD1 degradation.
abstract: MLN4924 is a first-in-class cancer drug that inhibits the Nedd8-activating enzyme (NAE). Herein, we report that MLN4924 inhibits Vpx/Vpr-induced SAMHD1 degradation by inhibiting the neddylation of E3 ubiquitin ligase and blocks macaque simian immunodeficiency virus (SIVmac) replication in myeloid cells. SAMHD1 is required for MLN4924-mediated SIVmac inhibition. Our findings indicate the potential efficacy of inhibiting neddylation as an antiretroviral strategy and identify the readily available anticancer drug MLN4924 as a candidate agent for that purpose.
authors.affiliation: School of Life Science, Tianjin University, Tianjin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Haoran
authors.initials: H
authors.lastname: Guo
authors.forename: Xianjun
authors.initials: X
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Qian
authors.forename: Kun
authors.initials: K
authors.lastname: Luo
authors.forename: Richard B
authors.initials: RB
authors.lastname: Markham
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Yu
mesh_terms: D000818:Animals; D003517:Cyclopentanes / Q000494:pharmacology*; D006801:Humans; D016180:Lentivirus Infections / Q000517:prevention & control*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D000076106:SAM Domain and HD Domain-Containing Protein 1
chemical_list: D003517:Cyclopentanes; D011743:Pyrimidines; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins; C539933:pevonedistat