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Gene Review

TRIM5  -  tripartite motif containing 5

Homo sapiens

Synonyms: RING finger protein 88, RNF88, TRIM5alpha, Tripartite motif-containing protein 5
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Disease relevance of TRIM5


High impact information on TRIM5


Chemical compound and disease context of TRIM5


Biological context of TRIM5

  • The ensuing TRIM5 publication flurry established a paradigm of innate immunity in which the protein lattice of an invading retroviral core, rather than double-stranded RNA or lipopolysaccharide, is recognized by a multimeric, cytoplasmic receptor [12].
  • Importantly, a TRIM5 haplotype containing the nonsynonymous SNP R136Q showed increased frequency among HIV-1-infected subjects relative to exposed seronegative persons, with an odds ratio of 5.49 (95% confidence interval = 1.83 to 16.45; P = 0.002) [13].
  • We sequenced the TRIM5 gene (excluding exon 5) and the 4.8-kb 5' putative regulatory region in genomic DNA from 110 HIV-1-infected subjects and 96 exposed seronegative persons, along with targeted gene sequencing in a further 30 HIV-1-infected individuals [13].
  • Human immunodeficiency virus type 1 (HIV-1) infection is blocked by the alpha isoform of macaque TRIM5 (TRIM5alpha(rh)) or by the product of the owl monkey TRIM5-cyclophilin A gene fusion (TRIMCyp) [14].
  • RNA interference was used to show that endogenous human TRIM5alpha does indeed restrict HIV-1, but the magnitude of this antiviral activity was not altered by disruption of the CA-CypA interaction or by elimination of CypA protein [15].

Anatomical context of TRIM5


Associations of TRIM5 with chemical compounds

  • Here, we exploit its modular domain organization and cyclosporine sensitivity to probe the kinetics and mechanism of TRIM5-mediated restriction [19].
  • Treatment of cells with geldanamycin, an Hsp90 inhibitor, resulted in disappearance or reduction of the TRIM5alpha-associated cytoplasmic bodies, yet exerted little effect on the restriction of retroviral infection [20].
  • Arsenic trioxide had complex and TRIM5alpha-independent enhancing effects on lentiviral but not NB-MLV infection [21].

Physical interactions of TRIM5

  • Disruption of Cyp A binding to CA partially relieved the block to HIV-1 infection imposed by several TRIM5alpha variants, but Cyp A-CA binding was not absolutely required for TRIM5alpha antiviral activity [22].

Regulatory relationships of TRIM5

  • We show here that interferon (IFN) upregulates TRIM5alpha mRNA expression in HeLa and HepG2 cells by performing Northern blot analysis and quantitative real-time PCR [23].

Other interactions of TRIM5


Analytical, diagnostic and therapeutic context of TRIM5


  1. Cyclophilin A is required for TRIM5{alpha}-mediated resistance to HIV-1 in Old World monkey cells. Berthoux, L., Sebastian, S., Sokolskaja, E., Luban, J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  2. Proteasome Inhibition Reveals that a Functional Preintegration Complex Intermediate Can Be Generated during Restriction by Diverse TRIM5 Proteins. Anderson, J.L., Campbell, E.M., Wu, X., Vandegraaff, N., Engelman, A., Hope, T.J. J. Virol. (2006) [Pubmed]
  3. Cyclophilin A, TRIM5, and resistance to human immunodeficiency virus type 1 infection. Luban, J. J. Virol. (2007) [Pubmed]
  4. Trim-cyclophilin A fusion proteins can restrict human immunodeficiency virus type 1 infection at two distinct phases in the viral life cycle. Yap, M.W., Dodding, M.P., Stoye, J.P. J. Virol. (2006) [Pubmed]
  5. Structural and functional insights into the B30.2/SPRY domain. Woo, J.S., Imm, J.H., Min, C.K., Kim, K.J., Cha, S.S., Oh, B.H. EMBO J. (2006) [Pubmed]
  6. Evolution of a cytoplasmic tripartite motif (TRIM) protein in cows that restricts retroviral infection. Si, Z., Vandegraaff, N., O'huigin, C., Song, B., Yuan, W., Xu, C., Perron, M., Li, X., Marasco, W.A., Engelman, A., Dean, M., Sodroski, J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Generation of HIV-1 derivatives that productively infect macaque monkey lymphoid cells. Kamada, K., Igarashi, T., Martin, M.A., Khamsri, B., Hatcho, K., Yamashita, T., Fujita, M., Uchiyama, T., Adachi, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Proteasome inhibitors uncouple rhesus TRIM5alpha restriction of HIV-1 reverse transcription and infection. Wu, X., Anderson, J.L., Campbell, E.M., Joseph, A.M., Hope, T.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  9. Cyclophilin A Renders Human Immunodeficiency Virus Type 1 Sensitive to Old World Monkey but Not Human TRIM5{alpha} Antiviral Activity. Keckesova, Z., Ylinen, L.M., Towers, G.J. J. Virol. (2006) [Pubmed]
  10. Removal of arginine 332 allows human TRIM5alpha to bind human immunodeficiency virus capsids and to restrict infection. Li, Y., Li, X., Stremlau, M., Lee, M., Sodroski, J. J. Virol. (2006) [Pubmed]
  11. Cyclophilin interactions with incoming human immunodeficiency virus type 1 capsids with opposing effects on infectivity in human cells. Hatziioannou, T., Perez-Caballero, D., Cowan, S., Bieniasz, P.D. J. Virol. (2005) [Pubmed]
  12. Cyclophilin, TRIM5, and innate immunity to HIV-1. Sokolskaja, E., Luban, J. Curr. Opin. Microbiol. (2006) [Pubmed]
  13. Genetic association of the antiviral restriction factor TRIM5alpha with human immunodeficiency virus type 1 infection. Speelmon, E.C., Livingston-Rosanoff, D., Li, S.S., Vu, Q., Bui, J., Geraghty, D.E., Zhao, L.P., McElrath, M.J. J. Virol. (2006) [Pubmed]
  14. Disruption of human TRIM5alpha antiviral activity by nonhuman primate orthologues. Berthoux, L., Sebastian, S., Sayah, D.M., Luban, J. J. Virol. (2005) [Pubmed]
  15. Cyclophilin A and TRIM5alpha independently regulate human immunodeficiency virus type 1 infectivity in human cells. Sokolskaja, E., Berthoux, L., Luban, J. J. Virol. (2006) [Pubmed]
  16. Trim5alpha protein restricts both HIV-1 and murine leukemia virus. Yap, M.W., Nisole, S., Lynch, C., Stoye, J.P. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  17. Arsenic counteracts human immunodeficiency virus type 1 restriction by various TRIM5 orthologues in a cell type-dependent manner. Sebastian, S., Sokolskaja, E., Luban, J. J. Virol. (2006) [Pubmed]
  18. Trim5{alpha} Accelerates Degradation of Cytosolic Capsid Associated with Productive HIV-1 Entry. Chatterji, U., Bobardt, M.D., Gaskill, P., Sheeter, D., Fox, H., Gallay, P.A. J. Biol. Chem. (2006) [Pubmed]
  19. Restriction of human immunodeficiency virus type 1 by TRIM-CypA occurs with rapid kinetics and independently of cytoplasmic bodies, ubiquitin, and proteasome activity. Perez-Caballero, D., Hatziioannou, T., Zhang, F., Cowan, S., Bieniasz, P.D. J. Virol. (2005) [Pubmed]
  20. TRIM5alpha association with cytoplasmic bodies is not required for antiretroviral activity. Song, B., Diaz-Griffero, F., Park, d.o. .H., Rogers, T., Stremlau, M., Sodroski, J. Virology (2005) [Pubmed]
  21. Restriction of feline immunodeficiency virus by Ref1, Lv1, and primate TRIM5alpha proteins. Saenz, D.T., Teo, W., Olsen, J.C., Poeschla, E.M. J. Virol. (2005) [Pubmed]
  22. Cyclophilin A: an auxiliary but not necessary cofactor for TRIM5alpha restriction of HIV-1. Stremlau, M., Song, B., Javanbakht, H., Perron, M., Sodroski, J. Virology (2006) [Pubmed]
  23. A retrovirus restriction factor TRIM5alpha is transcriptionally regulated by interferons. Asaoka, K., Ikeda, K., Hishinuma, T., Horie-Inoue, K., Takeda, S., Inoue, S. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  24. Functional replacement of the RING, B-box 2, and coiled-coil domains of tripartite motif 5alpha (TRIM5alpha) by heterologous TRIM domains. Li, X., Li, Y., Stremlau, M., Yuan, W., Song, B., Perron, M., Sodroski, J. J. Virol. (2006) [Pubmed]
  25. Inhibition of HIV-1 replication by simian restriction factors, TRIM5alpha and APOBEC3G. Sakuma, R., Noser, J.A., Ohmine, S., Ikeda, Y. Gene Ther. (2007) [Pubmed]
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