Cyclin L2 is a critical HIV dependency factor in macrophages that controls SAMHD1 abundance.

George Boateng Kyei, Xiaogang Cheng, Rashmi Ramani, Lee Ratner

Cell host & microbe 2015 Jan 14

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The restriction factor SAMHD1 limits HIV-1 replication in noncycling cells. SIV and HIV-2 overcome this restriction via the accessory protein Vpx, which targets SAMHD1 for degradation through interactions with the host ubiquitin ligase adaptor DCAF1. However, the factors used by HIV-1 to replicate in macrophages, despite the presence of the restriction factor SAMHD1, are unknown. Using a yeast two-hybrid screen, we identified cyclin L2 as a DCAF1-interacting protein required for HIV-1 replication in macrophages. Knockdown of cyclin L2 results in severe attenuation of HIV-1 replication in macrophages but not cycling cells, and this effect is lost in the absence of SAMHD1. Cyclin L2 and SAMHD1 form a molecular complex that is partially dependent on the presence of DCAF1 and results in SAMHD1 degradation in a proteasome- and DCAF1-dependent manner. Therefore, cyclin L2-mediated control of SAMHD1 levels in macrophages supports HIV-1 replication. Copyright © 2015 Elsevier Inc. All rights reserved.

Citation

George Boateng Kyei, Xiaogang Cheng, Rashmi Ramani, Lee Ratner. Cyclin L2 is a critical HIV dependency factor in macrophages that controls SAMHD1 abundance. Cell host & microbe. 2015 Jan 14;17(1):98-106