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TRIM5 is an innate immune sensor for the retrovirus capsid lattice
Open accessAbstract
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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“In DCs, TRIM5α binding to the capsid lattice also triggers signal transduction cascades resulting in the activation of the transcription factors AP-1 and NF-κB 59.”
From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [59]
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“Although this is insufficient to induce IFN production alone, these cascades synergize with other pathways, thus enhancing the IFN response 59.”
From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [59]
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The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys
Stremlau, M. H., Owens, C. M., Perron, M. J., Kießling, M. K., Autissier, P., & Sodroski, J. (2004) · Nature · doi:10.1038/nature02343 · Cited by 1,810
Integration of murine leukemia virus DNA depends on mitosis.
Roe, T., Reynolds, T. C., Yu, G., & Brown, P. O. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05858.x · Cited by 921
Stremlau, M. H., Perron, M. J., Lee, M. N., Li, Y., Song, B., Javanbakht, H., Diaz‐Griffero, F., Anderson, D. J., Sundquist, W. I., & Sodroski, J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509996103 · Cited by 736
Assembly and Analysis of Conical Models for the HIV-1 Core
Ganser, B. K., Li, S., Klishko, V. Y., Finch, J. T., & Sundquist, W. I. (1999) · Science · doi:10.1126/science.283.5398.80 · Cited by 671
Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1
Sayah, D. M., Sokolskaja, E., Berthoux, L., & Luban, J. (2004) · Nature · doi:10.1038/nature02777 · Cited by 662
Self-citationAn Atomic Model of the Interferon-β Enhanceosome
Panne, D., Maniatis, T., & Harrison, S. C. (2007) · Cell · doi:10.1016/j.cell.2007.05.019 · Cited by 625
Zeng, W., Sun, L., Jiang, X., Chen, X., Hou, F., Adhikari, A., Xu, M., & Chen, Z. J. (2010) · Cell · doi:10.1016/j.cell.2010.03.029 · Cited by 613
Direct activation of protein kinases by unanchored polyubiquitin chains
Xia, Z.-P., Sun, L., Chen, X., Pineda, G., Jiang, X., Adhikari, A., Zeng, W., & Chen, Z. J. (2009) · Nature · doi:10.1038/nature08247 · Cited by 570
X-Ray Structures of the Hexameric Building Block of the HIV Capsid
Pornillos, O., Ganser-Pornillos, B. K., Kelly, B. N., Hua, Y., Whitby, F. G., Stout, C. D., Sundquist, W. I., Hill, C. P., & Yeager, M. (2009) · Cell · doi:10.1016/j.cell.2009.04.063 · Cited by 523
Yan, N., Regalado-Magdos, A. D., Stiggelbout, B., Lee‐Kirsch, M. A., & Lieberman, J. (2010) · Nature Immunology · doi:10.1038/ni.1941 · Cited by 522
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Rahm, N. (2018) · Springer eBooks · doi:10.1007/978-1-4939-7101-5_370
TRIM5 Alpha and HIV-2 Infection
Jallow, S., & Simpson, S. (2018) · Springer eBooks · doi:10.1007/978-1-4939-7101-5_47
Rappaport, J. (2012) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.716147813.791552821
TRIM5 Alpha and HIV-2 Infection
Jallow, S., & Simpson, S. (2015) · Springer eBooks · doi:10.1007/978-1-4614-9610-6_47-1
Staller, S. (2021) · MOspace Institutional Repository (University of Missouri) · doi:10.32469/10355/91021
Interactions Between HIV-2 and Host Restriction Factors
Simpson, S., & Jallow, S. (2016) · Springer eBooks · doi:10.1007/978-1-4614-9610-6_41-2
Interactions Between HIV-2 and Host Restriction Factors
Simpson, S., & Jallow, S. (2018) · Springer eBooks · doi:10.1007/978-1-4939-7101-5_41
TRIM Protein Family and Viral Restriction
Nisole, S. (2018) · Springer eBooks · doi:10.1007/978-1-4939-7101-5_383
Recruitment of TRiC chaperonin in rotavirus viroplasms directly associates with virus replicationPreprint
Vetter, J., Papa, G., Tobler, K., Kley, M., Myers, M. P., Wiesendanger, M., Schraner, E. M., Burrone, Ó. R., Fraefel, C., & Eichwald, C. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.12.13.520363
A maturation defective HIV-1 activates cGASPreprint
Sumner, R. P., Blest, H. T. W., Lin, M., de Motes, C. M., & Towers, G. J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.04.14.536845
A frequent SNP in TRIM5α strongly enhances the innate immune response against LINE-1 elements
Lagisquet, J., Conrad, M., Wittmann, S., Volkmann, B., Weissinger, H., Sticht, H., & Gramberg, T. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1168589
A single dominant locus restricts retrovirus replication in YBR/Ei mice
Beilinson, H. A., Sevilleja, A., Spring, J., Benavides, F. J., Beilinson, V., Neokosmidis, N., & Golovkina, T. V. (2023) · Journal of Virology · doi:10.1128/jvi.00685-23
Twentyman, J., Khalifeh, A., Felton, A., Emerman, M., & OhAinle, M. (2023) · Figshare · doi:10.6084/m9.figshare.24013053
The KT Jeang retrovirology prize 2024: Walther Mothes
Mothes, W. (2024) · Retrovirology · doi:10.1186/s12977-024-00649-8
Self-citationIntrinsic Cellular Defenses (TRIMS) in Modulating Viral Infection and Immunity
García‐Sastre, A., & Miorin, L. (2025) · Elsevier eBooks · doi:10.1016/b978-0-12-824465-4.00284-2
A modified cyclosporine enhances lentivector transduction ex vivo and in vivo by degrading IFITM3
Annett, D., Critchley, B. J., Morling, K. L., Graham, B., Pingitore, V., Whittaker, T. E., Kurdi, N., Warne, J. M., Moula, S. E., León‐Rico, D., et al. (2026) · Molecular Therapy · doi:10.1016/j.ymthe.2026.07.056
Sharp, M. F., Harris, C., Mukherjee, C., Novakovic, S., Granger, E., Pujol, R. M., Muñoz‐Pujol, G., Shi, E. Z., Dun, K. A., Rosa, C. S., et al. (2025) · medRxiv · doi:10.1101/2025.10.29.25337140
Zhao, K. X. (2012) · Illinois Digital Environment for Access to Learning and Scholarship (University of Illinois at Urbana-Champaign)
Griffin, K. R. (2013) · D-Scholarship@Pitt (University of Pittsburgh)
Webb, A. E. (2015) · Dublin City University Open Access Institutional Repository (Dublin City University)
Hu, J., Song, L., Ning, M., Niu, X., Han, M., Gao, C., Feng, X., Cai, H., Li, T., Li, F., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26677244
Hu, J., Song, L., Ning, M., Niu, X., Han, M., Gao, C., Feng, X., Cai, H., Li, T., Li, F., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26677241
Twentyman, J., Khalifeh, A., Felton, A., Emerman, M., & OhAinle, M. (2023) · Figshare · doi:10.6084/m9.figshare.24013056
Hu, J., Song, L., Ning, M., Niu, X., Han, M., Gao, C., Feng, X., Cai, H., Li, T., Li, F., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26677253
Hu, J., Song, L., Ning, M., Niu, X., Han, M., Gao, C., Feng, X., Cai, H., Li, T., Li, F., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26677238
Hu, J., Song, L., Ning, M., Niu, X., Han, M., Gao, C., Feng, X., Cai, H., Li, T., Li, F., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26677247
Twentyman, J., Khalifeh, A., Felton, A., Emerman, M., & OhAinle, M. (2023) · Figshare · doi:10.6084/m9.figshare.24013050
Additional file 1 of HIV-1 with gag processing defects activates cGAS sensing
Sumner, R. P., Blest, H. T. W., Lin, M., Maluquer de Motes, C., & Towers, G. J. (2024) · Figshare · doi:10.6084/m9.figshare.25884984
Hu, J., Song, L., Ning, M., Niu, X., Han, M., Gao, C., Feng, X., Cai, H., Li, T., Li, F., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26677250
Virologie moléculaire d'un rétrovirus endogène humain fonctionnel
Lemaître, C. (2016) · theses.fr (ABES) · doi:10.70675/9964851dz8bdez4212zbebdz8e758164eb23
Gentili, M. (2017) · theses.fr (ABES) · doi:10.70675/93617cb4za4e9z4fdez831az0bf2b31aea90
Updates on the role of TRIM proteins in AIDS: molecular mechanisms and potential for interventions
Chen, J., Chen, S., Xu, Y., Wang, X., & Jiang, M. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1742036
TRIM5 integrates hypoglycemic stress and influenza infection
Lv, X., Jin, M., Wei, B., Wu, Z., Xie, D., Chen, H., Lv, W., He, J., Wu, Y., Xiao, Y., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-72791-0
PQBP1 couples HIV-1 capsid recognition to cGAS recruitment through conformational remodelingPreprint
Allen, D., Manna, A. K., Beusch, C. M., Zhang, T.-H., Ganser‐Pornillos, B. K., Piacentini, J., Oh, S., Prabhu, S., Mehta, A., Gordon, D. E., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.07.737097
Zhao, Y., Probert, S., Birkel, J., Liu, X., Shi, Y., Yang, O. S., Zhao, K., Lu, Y., & Smith, G. L. (2026) · PLoS Pathogens · doi:10.1371/journal.ppat.1014376
Arrambide, C. A. J., Karampoor, S., Abdelrahim, I. M., Maloletneva, N. V., & Mirzaei, R. (2026) · Journal of Medical Virology · doi:10.1002/jmv.71048
Broccolo, F., Sannino, A., Pollini, M., Paladini, F., Mourer, T., & Nunzio, F. D. (2026) · Pathogens · doi:10.3390/pathogens15070766
Crismani, W., Harris, C., Sharp, M. F., Mukherjee, C., Novakovic, S., Granger, E., Pujol, R. M., Muñoz‐Pujol, G., Shi, E., Dun, K. A., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-10063641/v1
Spi-B and IRF1 activate tumor immunogenicity downstream of the Epstein-Barr virus protein LMP1
Yamane, K., Kawano, Y., Ohki, S., Matayoshi, K., Morihara, N., Azuma, H., Yusei, O. T. A., Kitajima, Y., Asai, T., & Yasuda, T. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117824
Alkhedhairi, S. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118402
BindingDB (2023) · UC San Diego · doi:10.7270/q2t43z22
Studies on Cellular Host Factors Involved in the HIV-1 Life Cycle: A Dissertation
Serquiña, A. (2012) · eScholarship@UMassChan · doi:10.13028/2gzz-cy82
Role of Lentiviral Restriction Factors in Resistance to SIV Infection In Vivo
Aamer, H. (2013) · D-Scholarship@Pitt (University of Pittsburgh)
Innate Immunity in Simian Immunodeficiency Virus Infection
Reeves, R. K., & Bosinger, S. E. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-404734-1.00008-5
Metadata
- Authors
- Pertel, T., Hausmann, S., Morger, D., Züger, 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., Grütter, M. G., & Luban, J.
- Affiliations
- University of Geneva (CH)
- University of Zurich (CH)
- Yale University (US)
- Light Chain Bioscience (Switzerland) (CH)
- Inserm (FR)
- Corresponding author
- Luban, Jeremy
- ORCID
- Venue
- Nature
- Published
- 2011-04
- Volume
- 472
- Issue
- 7343
- Pages
- 361-365
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3081621
- OpenAlex
- W2057040546
- Cited by
- 645
- References
- 27
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 35 · 2023: 27 · 2022: 19 · 2021: 34 · 2020: 39 · 2019: 50 · 2018: 43 · 2017: 41 · 2016: 39 · 2015: 48 · 2014: 56 · 2013: 70 · 2012: 72
- FWCI
- 29.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- IRIS (submittedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Iris (University of Trento) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (59159, 128655, 122342, 3100A0)
- National Institutes of Health (3100A0-128655)
- National Institute of Allergy and Infectious Diseases (R01 AI59159, R01AI059159, R21AI087467)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- TRIM5, antiretroviral restriction factors, E3 ubiquitin ligase, pattern recognition receptors, innate immune signaling, K63-linked ubiquitin, TAK1, NF-κB signaling, retroviral infection
- MeSH terms
- Tripartite Motif Proteins, Antiviral Restriction Factors, MAP Kinase Kinase Kinase 7, Capsid, Carrier Proteins, Cell Line, Enzyme Activation, Humans, Immunity, Innate, Lipopolysaccharides, Protein Binding, Retroviridae, Transcription Factors, Signal Transduction, HIV-1, NF-kappa B, Transcription Factor AP-1, MAP Kinase Kinase Kinases, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Receptors, Pattern Recognition, HEK293 Cells
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