TRIM5 is an innate immune sensor for the retrovirus capsid lattice

Details

Serval ID
serval:BIB_7316B7F571A9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
TRIM5 is an innate immune sensor for the retrovirus capsid lattice
Journal
Nature
Author(s)
Pertel T., Hausmann S., Morger D., Zuger S., Guerra J., Lascano J., Reinhard C., Santoni F. A., Uchil P. D., Chatel L., Bisiaux A., Albert M. L., Strambio-De-Castillia C., Mothes W., Pizzato M., Grutter M. G., Luban J.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
Published
Issued date
2011
Volume
472
Number
7343
Pages
361-5
Language
english
Notes
Pertel, Thomas
Hausmann, Stephane
Morger, Damien
Zuger, Sara
Guerra, Jessica
Lascano, Josefina
Reinhard, Christian
Santoni, Federico A
Uchil, Pradeep D
Chatel, Laurence
Bisiaux, Aurelie
Albert, Matthew L
Strambio-De-Castillia, Caterina
Mothes, Walther
Pizzato, Massimo
Grutter, Markus G
Luban, Jeremy
eng
R21 AI087467/AI/NIAID NIH HHS/
R01 AI059159-06/AI/NIAID NIH HHS/
R21AI087467/AI/NIAID NIH HHS/
R01 AI059159/AI/NIAID NIH HHS/
R01AI59159/AI/NIAID NIH HHS/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
England
Nature. 2011 Apr 21;472(7343):361-5. doi: 10.1038/nature09976.
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 NFkappaB 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-kappaB-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/*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
Pubmed
Create date
20/05/2019 12:52
Last modification date
25/02/2020 6:26
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