TRIM5 is an innate immune sensor for the retrovirus capsid lattice

Article Article scientifique Article TRIM5 is an innate immune sensor for the retrovirus capsid lattice eng 2011 author Pertel Thomas 674561 author Hausmann Stéphane 29303 author Morger Damien author Züger Sara author Guerra Jessica 714290 author Lascano Maillard Maria Josefina 595217 author Reinhard Christian 698656 author Santoni Federico 681638 author Uchil Pradeep D author Chatel Laurence author Bisiaux Aurélie author Albert Matthew L author Strambio-De-Castillia Caterina author Mothes Walther author Pizzato Massimo 705520 author Grütter Markus G author Luban Jeremy 659379 361-365 10.1038/nature09976 21512573 0028-0836 TRIM5 is a RING domain-E3 ubiquitin ligase that restricts infection by human immunodeficiency virus (HIV)-1 and other retroviruses immediately following virus invasion of the target cell cytoplasm. Antiviral potency correlates with TRIM5 avidity for the retrovirion capsid lattice and several reports indicate that TRIM5 has a role in signal transduction, but the precise mechanism of restriction is unknown. Here we demonstrate that TRIM5 promotes innate immune signalling and that this activity is amplified by retroviral infection and interaction with the capsid lattice. Acting with the heterodimeric, ubiquitin-conjugating enzyme UBC13-UEV1A (also known as UBE2N-UBE2V1), TRIM5 catalyses the synthesis of unattached K63-linked ubiquitin chains that activate the TAK1 (also known as MAP3K7) kinase complex and stimulate AP-1 and NFκB signalling. Interaction with the HIV-1 capsid lattice greatly enhances the UBC13-UEV1A-dependent E3 activity of TRIM5 and challenge with retroviruses induces the transcription of AP-1 and NF-κB-dependent factors with a magnitude that tracks with TRIM5 avidity for the invading capsid. Finally, TAK1 and UBC13-UEV1A contribute to capsid-specific restriction by TRIM5. Thus, the retroviral restriction factor TRIM5 has two additional activities that are linked to restriction: it constitutively promotes innate immune signalling and it acts as a pattern recognition receptor specific for the retrovirus capsid lattice. Capsid/chemistry/immunology Carrier Proteins/genetics/immunology/metabolism Cell Line Enzyme Activation HEK293 Cells HIV-1/chemistry/immunology Humans Immunity, Innate/immunology Lipopolysaccharides/immunology/pharmacology MAP Kinase Kinase Kinases/metabolism NF-kappa B/metabolism Protein Binding Receptors, Pattern Recognition/immunology/metabolism Retroviridae/chemistry/immunology Signal Transduction/drug effects/immunology Transcription Factor AP-1/metabolism Transcription Factors/metabolism Ubiquitin/metabolism Ubiquitin-Conjugating Enzymes/metabolism Ubiquitin-Protein Ligases/genetics/immunology/metabolism Dewey 616 54 Département de microbiologie et médecine moléculaire 21B false Nature 472 7343 a3dc0412-a5e1-4414-95a1-b3f596a2339b Article (Published version) Restricted nature09976.pdf 575164 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire

Title	Published in	Year	Views	Downloads

HIV-1 innate immune detection and evasion		2013	745	878
TRIM5 is an innate immune sensor for the retrovirus capsid lattice	Nature	2011	447	1

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