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TRIM5 is an innate immune sensor for the retrovirus capsid lattice.

Thomas Pertel 1 Stéphane Hausmann 1 Damien Morger 2 Sara Züger 2 Jessica Guerra 1 Josefina Lascano 1 Christian Reinhard 1 Federico A. Santoni 1 Pradeep D. Uchil 3 Laurence Chatel 4 Aurélie Bisiaux 5 Matthew L. Albert 5 Caterina Strambio-De-Castillia 1 Walther Mothes 3 Massimo Pizzato 1 Markus G. Grütter 2 Jeremy Luban 1, *
* Corresponding author
1 Département de Microbiologie et Médecine moléculaire
2 Department of Biochemistry [Zurich]
3 Section of Microbial Pathogenesis
4 Novimmune SA
5 Immunobiologie des Cellules Dendritiques
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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01402086
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Submitted on : Thursday, November 24, 2016 - 11:11:09 AM
Last modification on : Wednesday, January 5, 2022 - 3:02:04 PM

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Thomas Pertel, Stéphane Hausmann, Damien Morger, Sara Züger, Jessica Guerra, et al.. TRIM5 is an innate immune sensor for the retrovirus capsid lattice.. Nature, Nature Publishing Group, 2011, 472 (7343), pp.361-5. ⟨10.1038/nature09976⟩. ⟨pasteur-01402086⟩

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