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Cell Rep. 2016 Jan 12;14(2):355-69. doi: 10.1016/j.celrep.2015.12.039. Epub 2015 Dec 31.

Endogenous TRIM5α Function Is Regulated by SUMOylation and Nuclear Sequestration for Efficient Innate Sensing in Dendritic Cells.

Author information

1
INSERM U941, University Institute of Hematology, Saint-Louis Hospital, 75010 Paris, France.
2
URA3015, Institut Pasteur, 75015 Paris, France.
3
Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
4
Institut Pasteur, Unité HIV, Inflammation et Persistance, 75015 Paris, France.
5
CEA-iMETI/Division of Immuno-Virology, Université Paris Sud, INSERM U1184, 92260 Fontenay-aux-Roses, France.
6
INSERM UMR-S 1124, Université Paris Descartes, 75006 Paris, France.
7
INSERM U941, University Institute of Hematology, Saint-Louis Hospital, 75010 Paris, France. Electronic address: nathalie.arhel@inserm.fr.

Abstract

During retroviral infection, viral capsids are subject to restriction by the cellular factor TRIM5α. Here, we show that dendritic cells (DCs) derived from human and non-human primate species lack efficient TRIM5α-mediated retroviral restriction. In DCs, endogenous TRIM5α accumulates in nuclear bodies (NB) that partly co-localize with Cajal bodies in a SUMOylation-dependent manner. Nuclear sequestration of TRIM5α allowed potent induction of type I interferon (IFN) responses during infection, mediated by sensing of reverse transcribed DNA by cGAS. Overexpression of TRIM5α or treatment with the SUMOylation inhibitor ginkgolic acid (GA) resulted in enforced cytoplasmic TRIM5α 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. TRIM5α regulation via SUMOylation-dependent nuclear sequestration adds to our understanding of how restriction factors are regulated.

PMID:
26748714
PMCID:
PMC4713866
DOI:
10.1016/j.celrep.2015.12.039
[Indexed for MEDLINE]
Free PMC Article

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