Journal
CELL REPORTS
Volume 14, Issue 2, Pages 355-369Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2015.12.039
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Funding
- Agence Nationale de Recherches sur le SIDA et les hepatites virales (ANRS)
- ATIP-Avenir program (INSERM)
- Deutsche Forschungsgemeinschaft (DFG)
- European FP7 HIT HIDDEN HIV'' [305762]
- DFG Leibniz award
- Advanced ERC Investigator grant
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During retroviral infection, viral capsids are subject to restriction by the cellular factor TRIM5 alpha. Here, we show that dendritic cells (DCs) derived from human and non-human primate species lack efficient TRIM5 alpha-mediated retroviral restriction. In DCs, endogenous TRIM5 alpha accumulates in nuclear bodies (NB) that partly co-localize with Cajal bodies in a SUMOylation-dependent manner. Nuclear sequestration of TRIM5 alpha allowed potent induction of type I interferon (IFN) responses during infection, mediated by sensing of reverse transcribed DNA by cGAS. Overexpression of TRIM5 alpha or treatment with the SUMOylation inhibitor ginkgolic acid (GA) resulted in enforced cytoplasmic TRIM5 alpha expression and restored efficient viral restriction but abrogated type I IFN production following infection. Our results suggest that there is an evolutionary trade-off specific to DCs in which restriction is minimized to maximize sensing. TRIM5 alpha regulation via SUMOylation-dependent nuclear sequestration adds to our understanding of how restriction factors are regulated.
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