Cyclin L2 is a critical HIV dependency factor in macrophages that controls samhd1 abundance

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

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)98-106
Number of pages9
JournalCell Host and Microbe
Volume17
Issue number1
DOIs
StatePublished - Jan 14 2015

Fingerprint Dive into the research topics of 'Cyclin L2 is a critical HIV dependency factor in macrophages that controls samhd1 abundance'. Together they form a unique fingerprint.

  • Cite this