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TRIM5 is an innate immune sensor for the retrovirus capsid lattice

Morger, Damien
Züger, Sara
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Published in Nature. 2011, vol. 472, no. 7343, p. 361-365
Abstract 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.
Keywords Capsid/chemistry/immunologyCarrier Proteins/genetics/immunology/metabolismCell LineEnzyme ActivationHEK293 CellsHIV-1/chemistry/immunologyHumansImmunity, Innate/immunologyLipopolysaccharides/immunology/pharmacologyMAP Kinase Kinase Kinases/metabolismNF-kappa B/metabolismProtein BindingReceptors, Pattern Recognition/immunology/metabolismRetroviridae/chemistry/immunologySignal Transduction/drug effects/immunologyTranscription Factor AP-1/metabolismTranscription Factors/metabolismUbiquitin/metabolismUbiquitin-Conjugating Enzymes/metabolismUbiquitin-Protein Ligases/genetics/immunology/metabolism
PMID: 21512573
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PERTEL, Thomas et al. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. In: Nature, 2011, vol. 472, n° 7343, p. 361-365. doi: 10.1038/nature09976 https://archive-ouverte.unige.ch/unige:92031

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