A first-in-class NAE inhibitor, MLN4924, blocks lentiviral infection in myeloid cells by disrupting neddylation-dependent Vpx-mediated SAMHD1 degradation

Wei Wei, Haoran Guo, Xianjun Liu, Hong Zhang, Lei Qian, Kun Luo, Richard B. Markham, Xiao Fang Yua

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)745-751
Number of pages7
JournalJournal of virology
Volume88
Issue number1
DOIs
StatePublished - Jan 1 2014

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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