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Journal articles
Endogenous TRIM5α Function Is Regulated by SUMOylation and Nuclear Sequestration for Efficient Innate Sensing in Dendritic Cells
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.
Cited literature [58 references]
https://hal-pasteur.archives-ouvertes.fr/pasteur-01960638
Contributor : Brigitte Bidault Connect in order to contact the contributor
Submitted on : Wednesday, December 19, 2018 - 3:00:15 PM
Last modification on : Thursday, October 21, 2021 - 5:24:02 PM
Long-term archiving on: : Wednesday, March 20, 2019 - 11:11:14 PM
Contributor : Brigitte Bidault Connect in order to contact the contributor
Submitted on : Wednesday, December 19, 2018 - 3:00:15 PM
Last modification on : Thursday, October 21, 2021 - 5:24:02 PM
Long-term archiving on: : Wednesday, March 20, 2019 - 11:11:14 PM
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