Wei Wei, Guo Haoran, Liu Xianjun, Zhang Hong, Qian Lei, Luo Kun, Markham Richard B, Yu Xiao-Fang
School of Life Science, Tianjin University, Tianjin, China.
J Virol. 2014 Jan;88(1):745-51. doi: 10.1128/JVI.02568-13. Epub 2013 Oct 23.
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.
MLN4924是一种一流的抗癌药物,可抑制Nedd8激活酶(NAE)。在此,我们报告MLN4924通过抑制E3泛素连接酶的Neddylation来抑制Vpx/Vpr诱导的SAMHD1降解,并阻断猕猴猿猴免疫缺陷病毒(SIVmac)在髓细胞中的复制。SAMHD1是MLN4924介导的SIVmac抑制所必需的。我们的研究结果表明,抑制Neddylation作为一种抗逆转录病毒策略具有潜在疗效,并确定现成的抗癌药物MLN4924作为该目的的候选药物。