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. Author manuscript; available in PMC: 2014 Aug 12.
Published in final edited form as: Cell Host Microbe. 2014 Feb 12;15(2):125–127. doi: 10.1016/j.chom.2014.01.012

Figure 1. HIV-1 Vpr Subverts the SLX4 Complex to Promote G2/M Arrest and Escape from Innate Immune Sensing.

Figure 1

Because of the potentially damaging effect of the structure-specific endonucleases bound to SLX4, the SLX4com is kept inactive during the G1 and S phases of the cell cycle. Direct interaction of Vpr with SLX4 increases binding of VPRBP to the complex and induces the recruitment of kinase active PLK1 to the SLX4com. The resulting Vpr-mediated remodeling of the SLX4com causes the phosphorylation of EME1 and the ubiquitination of MUS81. These modifications trigger the activation of the heteromeric EME1-MUS81 endonuclease complex and lead to the processing of HIV-1 DNA, a condition that promotes evasion from innate immune sensing. In parallel, untimely activation of the SLX4com by Vpr prior to G2/M results in replication stress and abnormal processing of replication forks, which in turn trigger signaling pathways that ultimately arrest cells at the G2-to-M transition.