TRIM E3 Ligases Interfere with Early and Late Stages of the Retroviral Life Cycle

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2008 Feb 6

PMID 18248090

Citations 125

Authors

Pradeep D Uchil

Brian D Quinlan

Wai-Tsing Chan

Joseph M Luna

Walther Mothes

Affiliations

Soon will be listed here.

Abstract

Members of the TRIpartite interaction Motif (TRIM) family of E3 ligases have been shown to exhibit antiviral activities. Here we report a near comprehensive screen for antiretroviral activities of 55 TRIM proteins (36 human, 19 mouse). We identified approximately 20 TRIM proteins that, when transiently expressed in HEK293 cells, affect the entry or release of human immunodeficiency virus 1 (HIV), murine leukemia virus (MLV), or avian leukosis virus (ALV). While TRIM11 and 31 inhibited HIV entry, TRIM11 enhanced N-MLV entry by interfering with Ref1 restriction. Strikingly, many TRIM proteins affected late stages of the viral life cycle. Gene silencing of endogenously expressed TRIM 25, 31, and 62 inhibited viral release indicating that they play an important role at late stages of the viral life cycle. In contrast, downregulation of TRIM11 and 15 enhanced virus release suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells.

Citing Articles

Analysis of Hepatic Lentiviral Vector Transduction: Implications for Preclinical Studies and Clinical Gene Therapy Protocols.

Hu P, Hao Y, Tang W, Diering G, Zou F, Kafri T Viruses. 2025; 17(2).

PMID: 40007031 PMC: 11861806. DOI: 10.3390/v17020276.

Heightened expression of type I interferon signaling genes in CD4 T cells from acutely HIV-1-infected women is associated with lower viral loads.

El-Badry E, Chen L, Ghneim K, Li Z, Brooks K, Rhodes J Front Immunol. 2025; 15:1507530.

PMID: 39902043 PMC: 11788160. DOI: 10.3389/fimmu.2024.1507530.

Evasion of the Antiviral Innate Immunity by PRV.

Wang C, Li L, Zhai X, Chang H, Liu H Int J Mol Sci. 2024; 25(23).

PMID: 39684850 PMC: 11642419. DOI: 10.3390/ijms252313140.

Mechanistic Role of TRIM26 in Viral Infection and Host Defense.

Sharma M, Liu K, Wei J, Ma Z, Qiu Y Genes (Basel). 2024; 15(11).

PMID: 39596676 PMC: 11594267. DOI: 10.3390/genes15111476.

The KT Jeang retrovirology prize 2024: Walther Mothes.

Mothes W Retrovirology. 2024; 21(1):16.

PMID: 39449025 PMC: 11515334. DOI: 10.1186/s12977-024-00649-8.

References

Schweiger S, Foerster J, Lehmann T, Suckow V, Muller Y, Walter G . The Opitz syndrome gene product, MID1, associates with microtubules. Proc Natl Acad Sci U S A. 1999; 96(6):2794-9. PMC: 15848. DOI: 10.1073/pnas.96.6.2794. View

Gack M, Shin Y, Joo C, Urano T, Liang C, Sun L . TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature. 2007; 446(7138):916-920. DOI: 10.1038/nature05732. View

Towers G, Goff S . Post-entry restriction of retroviral infections. AIDS Rev. 2003; 5(3):156-64. View

Keckesova Z, Ylinen L, Towers G . The human and African green monkey TRIM5alpha genes encode Ref1 and Lv1 retroviral restriction factor activities. Proc Natl Acad Sci U S A. 2004; 101(29):10780-5. PMC: 490011. DOI: 10.1073/pnas.0402474101. View

Sawyer S, Wu L, Emerman M, Malik H . Positive selection of primate TRIM5alpha identifies a critical species-specific retroviral restriction domain. Proc Natl Acad Sci U S A. 2005; 102(8):2832-7. PMC: 549489. DOI: 10.1073/pnas.0409853102. View

Buchner G, Montini E, Andolfi G, Quaderi N, Cainarca S, Messali S . MID2, a homologue of the Opitz syndrome gene MID1: similarities in subcellular localization and differences in expression during development. Hum Mol Genet. 1999; 8(8):1397-407. DOI: 10.1093/hmg/8.8.1397. View

Sherer N, Lehmann M, Jimenez-Soto L, Ingmundson A, Horner S, Cicchetti G . Visualization of retroviral replication in living cells reveals budding into multivesicular bodies. Traffic. 2003; 4(11):785-801. DOI: 10.1034/j.1600-0854.2003.00135.x. View

Perron M, Stremlau M, Lee M, Javanbakht H, Song B, Sodroski J . The human TRIM5alpha restriction factor mediates accelerated uncoating of the N-tropic murine leukemia virus capsid. J Virol. 2006; 81(5):2138-48. PMC: 1865943. DOI: 10.1128/JVI.02318-06. View

Sherer N, Lehmann M, Jimenez-Soto L, Horensavitz C, Pypaert M, Mothes W . Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission. Nat Cell Biol. 2007; 9(3):310-5. PMC: 2628976. DOI: 10.1038/ncb1544. View

10.

Nisole S, Stoye J, Saib A . TRIM family proteins: retroviral restriction and antiviral defence. Nat Rev Microbiol. 2005; 3(10):799-808. DOI: 10.1038/nrmicro1248. View

11.

Fridell R, Harding L, Bogerd H, Cullen B . Identification of a novel human zinc finger protein that specifically interacts with the activation domain of lentiviral Tat proteins. Virology. 1995; 209(2):347-57. DOI: 10.1006/viro.1995.1266. View

12.

Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L . The tripartite motif family identifies cell compartments. EMBO J. 2001; 20(9):2140-51. PMC: 125245. DOI: 10.1093/emboj/20.9.2140. View

13.

Mothes W, Boerger A, Narayan S, Cunningham J, Young J . Retroviral entry mediated by receptor priming and low pH triggering of an envelope glycoprotein. Cell. 2000; 103(4):679-89. DOI: 10.1016/s0092-8674(00)00170-7. View

14.

Bieniasz P . Intrinsic immunity: a front-line defense against viral attack. Nat Immunol. 2004; 5(11):1109-15. DOI: 10.1038/ni1125. View

15.

Everett R, Chelbi-Alix M . PML and PML nuclear bodies: implications in antiviral defence. Biochimie. 2007; 89(6-7):819-30. DOI: 10.1016/j.biochi.2007.01.004. View

16.

Sakuma R, Noser J, Ohmine S, Ikeda Y . Rhesus monkey TRIM5alpha restricts HIV-1 production through rapid degradation of viral Gag polyproteins. Nat Med. 2007; 13(5):631-5. DOI: 10.1038/nm1562. View

17.

Sayah D, Sokolskaja E, Berthoux L, Luban J . Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1. Nature. 2004; 430(6999):569-73. DOI: 10.1038/nature02777. View

18.

Tissot C, Mechti N . Molecular cloning of a new interferon-induced factor that represses human immunodeficiency virus type 1 long terminal repeat expression. J Biol Chem. 1995; 270(25):14891-8. DOI: 10.1074/jbc.270.25.14891. View

19.

Meroni G, Diez-Roux G . TRIM/RBCC, a novel class of 'single protein RING finger' E3 ubiquitin ligases. Bioessays. 2005; 27(11):1147-57. DOI: 10.1002/bies.20304. View

20.

Ishikawa H, Tachikawa H, Miura Y, Takahashi N . TRIM11 binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105) through the ubiquitin-proteasome system. FEBS Lett. 2006; 580(20):4784-92. DOI: 10.1016/j.febslet.2006.07.066. View