The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Host Innate Immune Receptors and Beyond: Making Sense of Microbial Infections
Ishii, K. J., Koyama, S., Nakagawa, A., Coban, C., & Akira, S. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.05.003 · Cited by 509
Atomic-level modelling of the HIV capsid
Pornillos, O., Ganser-Pornillos, B. K., & Yeager, M. (2011) · Nature · doi:10.1038/nature09640 · Cited by 372
TRIM5α mediates the postentry block to N-tropic murine leukemia viruses in human cells
Perron, M. J., Stremlau, M. H., Song, B., Ulm, W., Mulligan, R. C., & Sodroski, J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403364101 · Cited by 290
Kornbluth, R. S., Oh, P., Munis, J. R., Cleveland, P. H., & Richman, D. D. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.169.3.1137 · Cited by 270
Shi, M., Deng, W., Bi, E., Mao, K., Ji, Y., Lin, G., Wu, X., Tao, Z., Li, Z., Cai, X., et al. (2008) · Nature Immunology · doi:10.1038/ni1577 · Cited by 257
Hexagonal assembly of a restricting TRIM5α protein
Ganser‐Pornillos, B. K., Chandrasekaran, V., Pornillos, O., Sodroski, J., Sundquist, W. I., & Yeager, M. J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013426108 · Cited by 248
TRIM5α selectively binds a restriction-sensitive retroviral capsid
Sebastian, S., & Luban, J. (2005) · Retrovirology · doi:10.1186/1742-4690-2-40 · Cited by 247
Self-citationCyclophilin A, TRIM5, and Resistance to Human Immunodeficiency Virus Type 1 Infection
Luban, J. (2007) · Journal of Virology · doi:10.1128/jvi.01519-06 · Cited by 147
Self-citationCyclophilin A is required for TRIM5α-mediated resistance to HIV-1 in Old World monkey cells
Berthoux, L., Sebastian, S., Sokolskaja, E., & Luban, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505659102 · Cited by 146
Self-citationPotent inhibition of HIV-1 by TRIM5-cyclophilin fusion proteins engineered from human components
Neagu, M. R., Ziegler, P., Pertel, T., Strambio‐De‐Castillia, C., Grütter, C., Martinetti, G., Mazzucchelli, L., Grütter, M. G., Manz, M. G., & Luban, J. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39354 · Cited by 127
Self-citationLangelier, C., Sandrin, V., Eckert, D. M., Christensen, D. E., Chandrasekaran, V., Alam, S. L., Aiken, C., Olsen, J. C., Kar, A. K., Sodroski, J., et al. (2008) · Journal of Virology · doi:10.1128/jvi.01562-08 · Cited by 120
Structural Basis for the Lack of E2 Interaction in the RING Domain of TRAF2
Yin, Q., Lamothe, B., Darnay, B. G., & Wu, H. (2009) · Biochemistry · doi:10.1021/bi901462e · Cited by 117
Sokolskaja, E., Berthoux, L., & Luban, J. (2006) · Journal of Virology · doi:10.1128/jvi.80.6.2855-2862.2006 · Cited by 103
Self-citationAs 2 O 3 Enhances Retroviral Reverse Transcription and Counteracts Ref1 Antiviral Activity
Berthoux, L., Towers, G. J., Gurer, C., Salomoni, P., Pandolfi, P. P., & Luban, J. (2003) · Journal of Virology · doi:10.1128/jvi.77.5.3167-3180.2003 · Cited by 73
Self-citationHuman Trim5α has additional activities that are uncoupled from retroviral capsid recognition
Tareen, S. U., & Emerman, M. (2010) · Virology · doi:10.1016/j.virol.2010.09.018 · Cited by 63
HIV immunology needs a new direction
Medzhitov, R. M., & Littman, D. R. (2008) · Nature · doi:10.1038/455591a · Cited by 32
Ulm, J. W., Perron, M. J., Sodroski, J., & Mulligan, R. C. (2007) · Virology · doi:10.1016/j.virol.2006.09.048 · Cited by 25
Cited by
Sorted by citations
van der Harst, P., & Verweij, N. (2018) · Circulation Research · doi:10.1161/circresaha.117.312086 · Cited by 1,141
Interferon-Stimulated Genes: What Do They All Do?
Schoggins, J. W. (2019) · Annual Review of Virology · doi:10.1146/annurev-virology-092818-015756 · Cited by 1,036
TRIM Family Proteins: Roles in Autophagy, Immunity, and Carcinogenesis
Hatakeyama, S. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.01.002 · Cited by 955
Ni, Y., Lempp, F. A., Mehrle, S., Nkongolo, S., Kaufman, C., Fälth, M., Stindt, J., Königer, C., Nassal, M., Kubitz, R., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.12.024 · Cited by 807
CEACAM1 regulates TIM-3-mediated tolerance and exhaustion
Huang, Y.-H., Zhu, C., Kondo, Y., Anderson, A. C., Gandhi, A., Russell, A., Dougan, S. K., Petersen, B.-S., Melum, E., Pertel, T., et al. (2015) · Nature · doi:10.1038/nature13848 · Cited by 717
Self-citation
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
