title: 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.
authors.affiliation: INSERM U941, University Institute of Hematology, Saint-Louis Hospital, 75010 Paris, France.
authors.forename: Débora M
authors.initials: DM
authors.lastname: Portilho
authors.affiliation: INSERM U941, University Institute of Hematology, Saint-Louis Hospital, 75010 Paris, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Fernandez
authors.affiliation: URA3015, Institut Pasteur, 75015 Paris, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Ringeard
authors.affiliation: INSERM U941, University Institute of Hematology, Saint-Louis Hospital, 75010 Paris, France.
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Machado
authors.affiliation: INSERM U941, University Institute of Hematology, Saint-Louis Hospital, 75010 Paris, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Boulay
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Martha
authors.initials: M
authors.lastname: Mayer
authors.affiliation: Institut Pasteur, Unité HIV, Inflammation et Persistance, 75015 Paris, France.
authors.forename: Michaela
authors.initials: M
authors.lastname: Müller-Trutwin
authors.affiliation: CEA-iMETI/Division of Immuno-Virology, Université Paris Sud, INSERM U1184, 92260 Fontenay-aux-Roses, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Beignon
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
authors.affiliation: INSERM UMR-S 1124, Université Paris Descartes, 75006 Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Nisole
authors.affiliation: INSERM U941, University Institute of Hematology, Saint-Louis Hospital, 75010 Paris, France. Electronic address: nathalie.arhel@inserm.fr.
authors.forename: Nathalie J
authors.initials: NJ
authors.lastname: Arhel
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000378:metabolism*; D006801:Humans; D008253:Macaca mulatta; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D058207:Sumoylation; D044767:Ubiquitin-Protein Ligases
chemical_list: D011506:Proteins; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases