期刊
CELL
卷 161, 期 6, 页码 1293-1305出版社
CELL PRESS
DOI: 10.1016/j.cell.2015.04.050
关键词
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资金
- NIH Common Funds Project at the University of Michigan [U24 DK097153]
- NIAID [P01 CA177322, P01 AI090935, R01 AI105184, U19 AI106754]
- NIGMS [P50 GM085764]
- James B. Pendleton Charitable Trust
Dendritic cells (DCs) play a critical role in the immune response to viral infection through the facilitation of cell-intrinsic antiviral activity and the activation of adaptive immunity. HIV-1 infection of DCs triggers an IRF3-dependent innate immune response, which requires the activity of cyclic GAMP synthase (cGAS). We report the results of a targeted RNAi screen utilizing primary human monocyte-derived DCs (MDDCs) to identify immune regulators that directly interface with HIV-1-encoded features to initiate this innate response. Polyglutamine binding protein 1 (PQBP1) emerged as a strong candidate through this analysis. We found that PQBP1 directly binds to reverse-transcribed HIV-1 DNA and interacts with cGAS to initiate an IRF3-dependent innate response. MDDCs derived from Renpenning syndrome patients, who harbor mutations in the PQBP1 locus, possess a severely attenuated innate immune response to HIV-1 challenge, underscoring the role of PQBP1 as a proximal innate sensor of a HIV-1 infection.
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