期刊
CELL HOST & MICROBE
卷 16, 期 6, 页码 722-735出版社
CELL PRESS
DOI: 10.1016/j.chom.2014.10.014
关键词
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资金
- NIH [RO1AI051192, R56AI051192, RO1AI046998]
- Burroughs Wellcome Fund
- University of Michigan Research Training in Experimental Immunology Training Grant [T32AI007413]
- Medical Scientist Training Grant [5T32GM007863]
- University of Michigan Molecular Mechanisms in Microbial Pathogenesis Training Grant [5T32AI007528]
The HIV-1 accessory protein Vpr enhances infection of primary macrophages through unknown mechanisms. Recent studies demonstrated that Vpr interactions with the cellular DCAF1-DDB1-CUL4 E3 ubiquitin ligase complex limit activation of innate immunity and interferon (IFN) induction. We describe a restriction mechanism that targets the HIV-1 envelope protein Env, but is overcome by Vpr and its interaction with DCAF1. This restriction is active in the absence of Vpr in HIV-1-infected primary macrophages and macrophage-epithelial cell heterokaryons, but not epithelial cell lines. HIV-1-infected macrophages lacking Vpr express more IFN following infection, target Env for lysosomal degradation, and produce fewer Env-containing virions. Conversely, Vpr expression reduces IFN induction, rescues Env expression, and enhances virion release. Addition of IFN or silencing DCAF1 reduces the amount of cell-associated Env and virion production in wild-type HIV-1-infected primary macrophages. These findings provide insight into an IFN-stimulated macrophage-specific restriction pathway targeting HIV-1 Env that is counteracted by Vpr.
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