Gene Symbol: TRIM5alpha
Description: tripartite motif containing 5
Alias: RNF88, TRIM5alpha, tripartite motif-containing protein 5, RING-type E3 ubiquitin transferase TRIM5, ring finger protein 88, tripartite motif containing 5 transcript variant iota, tripartite motif containing 5 transcript variant kappa, tripartite motif protein TRIM5
Species: human
Products:     TRIM5alpha

Top Publications

  1. Asaoka K, Ikeda K, Hishinuma T, Horie Inoue K, Takeda S, Inoue S. A retrovirus restriction factor TRIM5alpha is transcriptionally regulated by interferons. Biochem Biophys Res Commun. 2005;338:1950-6 pubmed
    b>TRIM5alpha is a member of tripartite motif protein family and recently identified as a restriction factor for retroviral infection in a species-specific manner...
  2. Li X, Song B, Xiang S, Sodroski J. Functional interplay between the B-box 2 and the B30.2(SPRY) domains of TRIM5alpha. Virology. 2007;366:234-44 pubmed
    The retroviral restriction factors, TRIM5alpha and TRIMCyp, consist of RING and B-box 2 domains separated by a coiled coil from carboxy-terminal domains. These carboxy-terminal domains (the B30...
  3. Sakuma R, Mael A, Ikeda Y. Alpha interferon enhances TRIM5alpha-mediated antiviral activities in human and rhesus monkey cells. J Virol. 2007;81:10201-6 pubmed
    Dominant, constitutively expressed antiretroviral factors, including TRIM5alpha and APOBEC3 proteins, are distinguished from the conventional innate immune systems and are classified as intrinsic immunity factors...
  4. Tareen S, Emerman M. Human Trim5? has additional activities that are uncoupled from retroviral capsid recognition. Virology. 2011;409:113-20 pubmed publisher
    ..Our results demonstrate functions of Trim5? that are not dependent on recognizing the retroviral capsid...
  5. Neagu M, Ziegler P, Pertel T, Strambio de Castillia C, Grütter C, Martinetti G, et al. Potent inhibition of HIV-1 by TRIM5-cyclophilin fusion proteins engineered from human components. J Clin Invest. 2009;119:3035-47 pubmed publisher
    ..The anti-HIV-1 activity of hT5Cyp was surprisingly more effective than that of the well-characterized rhesus TRIM5alpha, especially in T cells...
  6. Ohmine S, Sakuma R, Sakuma T, Thatava T, Takeuchi H, Ikeda Y. The antiviral spectra of TRIM5? orthologues and human TRIM family proteins against lentiviral production. PLoS ONE. 2011;6:e16121 pubmed publisher
  7. Maillard P, Reynard S, Serhan F, Turelli P, Trono D. Interfering residues narrow the spectrum of MLV restriction by human TRIM5alpha. PLoS Pathog. 2007;3:e200 pubmed publisher
    b>TRIM5alpha is a restriction factor that limits infection of human cells by so-called N- but not B- or NB-tropic strains of murine leukemia virus (MLV)...
  8. Van Manen D, Rits M, Beugeling C, van Dort K, Schuitemaker H, Kootstra N. The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection. PLoS Pathog. 2008;4:e18 pubmed publisher
    The antiviral factor tripartite interaction motif 5alpha (Trim5alpha) restricts a broad range of retroviruses in a species-specific manner...
  9. Veillette M, Bichel K, Pawlica P, Freund S, Plourde M, Pham Q, et al. The V86M mutation in HIV-1 capsid confers resistance to TRIM5? by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Retrovirology. 2013;10:25 pubmed publisher
    ..However, V86M does not seem to relieve restriction of a spreading HIV-1 infection by TRIM5?hu mutants, underscoring context-specific restriction mechanisms. ..

More Information


  1. Battivelli E, Migraine J, Lecossier D, Matsuoka S, Perez Bercoff D, Saragosti S, et al. Modulation of TRIM5alpha activity in human cells by alternatively spliced TRIM5 isoforms. J Virol. 2011;85:7828-35 pubmed publisher
    ..Specific knockdown of TRIM5? increases TRIM5? activity in human U373-X4 cells, indicating that physiological levels of expression of truncated TRIM5 isoforms in human cells can reduce the activity of TRIM5?. ..
  2. Li Y, Li X, Stremlau M, Lee M, Sodroski J. Removal of arginine 332 allows human TRIM5alpha to bind human immunodeficiency virus capsids and to restrict infection. J Virol. 2006;80:6738-44 pubmed
    Human TRIM5alpha (TRIM5alpha(hu)) only modestly inhibits human immunodeficiency virus type 1 (HIV-1) and does not inhibit simian immunodeficiency virus (SIV(mac)). Alteration of arginine 332 in the TRIM5alpha(hu) B30...
  3. Langelier C, Sandrin V, Eckert D, Christensen D, Chandrasekaran V, Alam S, et al. Biochemical characterization of a recombinant TRIM5alpha protein that restricts human immunodeficiency virus type 1 replication. J Virol. 2008;82:11682-94 pubmed publisher
    The rhesus monkey intrinsic immunity factor TRIM5alpha(rh) recognizes incoming capsids from a variety of retroviruses, including human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV), and inhibits the ..
  4. Zhang X, Kondo M, Chen J, Miyoshi H, Suzuki H, Ohashi T, et al. Inhibitory effect of human TRIM5alpha on HIV-1 production. Microbes Infect. 2010;12:768-77 pubmed publisher
    Tripartite motif-containing 5 isoform-alpha (TRIM5alpha), a host restriction factor, blocks infection of some retroviruses at a post-entry, pre-integration stage in a species-specific manner. A recent report by Sakuma et al...
  5. Nakayama E, Shioda T. Anti-retroviral activity of TRIM5 alpha. Rev Med Virol. 2010;20:77-92 pubmed publisher
    ..Accurate structural analysis of the binding surface between the viral capsid protein and TRIM5 alpha SPRY is thus required for the development of new antiretroviral drugs that enhance anti-HIV-1 activity of human TRIM5 alpha. ..
  6. Battivelli E, Lecossier D, Matsuoka S, Migraine J, Clavel F, Hance A. Strain-specific differences in the impact of human TRIM5alpha, different TRIM5alpha alleles, and the inhibition of capsid-cyclophilin A interactions on the infectivity of HIV-1. J Virol. 2010;84:11010-9 pubmed publisher
    ..Taken together, these findings support a model in which three interlinked factors--capsid sequence, CypA levels, and TRIM5?--interact to determine capsid stability and therefore viral infectivity. ..
  7. Ganser Pornillos B, Yeager M, Sundquist W. The structural biology of HIV assembly. Curr Opin Struct Biol. 2008;18:203-17 pubmed publisher
  8. Harris R, Hultquist J, Evans D. The restriction factors of human immunodeficiency virus. J Biol Chem. 2012;287:40875-83 pubmed publisher
    ..These HIV restriction and counter-restriction mechanisms suggest strategies for new therapeutic interventions...
  9. Diaz Griffero F, Li X, Javanbakht H, Song B, Welikala S, Stremlau M, et al. Rapid turnover and polyubiquitylation of the retroviral restriction factor TRIM5. Virology. 2006;349:300-15 pubmed
    b>TRIM5alpha and TRIMCyp are retroviral restriction factors that, like other members of the tripartite motif (TRIM) family, contain RING, B-box 2 and coiled-coil domains...
  10. Mische C, Javanbakht H, Song B, Diaz Griffero F, Stremlau M, Strack B, et al. Retroviral restriction factor TRIM5alpha is a trimer. J Virol. 2005;79:14446-50 pubmed
    The retrovirus restriction factor TRIM5alpha targets the viral capsid soon after entry. Here we show that the TRIM5alpha protein oligomerizes into trimers. The TRIM5alpha coiled-coil and B30...
  11. Kuroishi A, Bozek K, Shioda T, Nakayama E. A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Retrovirology. 2010;7:58 pubmed publisher
    ..Unexpectedly, HIV-1 with this mutation became resistant to CM TRIM5 alpha-mediated restriction. ..
  12. Speelmon E, Livingston Rosanoff D, Li S, Vu Q, Bui J, Geraghty D, et al. Genetic association of the antiviral restriction factor TRIM5alpha with human immunodeficiency virus type 1 infection. J Virol. 2006;80:2463-71 pubmed
    The innate antiviral factor TRIM5alpha restricts the replication of some retroviruses through its interaction with the viral capsid protein, leading to abortive infection...
  13. BLACK L, Aiken C. TRIM5alpha disrupts the structure of assembled HIV-1 capsid complexes in vitro. J Virol. 2010;84:6564-9 pubmed publisher
    The host restriction factor TRIM5alpha provides intrinsic defense against retroviral infections in mammalian cells...
  14. Zhang F, Hatziioannou T, Perez Caballero D, Derse D, Bieniasz P. Antiretroviral potential of human tripartite motif-5 and related proteins. Virology. 2006;353:396-409 pubmed
    b>TRIM5alpha is a potent inhibitor of infection by diverse retroviruses and is encoded by one of a large family of TRIM genes...
  15. Campbell E, Dodding M, Yap M, Wu X, Gallois Montbrun S, Malim M, et al. TRIM5 alpha cytoplasmic bodies are highly dynamic structures. Mol Biol Cell. 2007;18:2102-11 pubmed
    ..Therefore, TRIM5 alpha cytoplasmic bodies are dynamic structures more consistent with a role in function or regulation rather than protein aggregates or inclusion bodies that represent dead-end static structures. ..
  16. Torimiro J, Javanbakht H, Diaz Griffero F, Kim J, Carr J, Carrington M, et al. A rare null allele potentially encoding a dominant-negative TRIM5alpha protein in Baka pygmies. Virology. 2009;391:140-7 pubmed publisher
    ..b>TRIM5alpha is a restriction factor that can decrease the susceptibility of cells of particular mammalian species to ..
  17. Blanco Melo D, Venkatesh S, Bieniasz P. Intrinsic cellular defenses against human immunodeficiency viruses. Immunity. 2012;37:399-411 pubmed publisher
    ..We also speculate on how restriction factors arose, how they might interact with the conventional innate and adaptive immune systems, and how an understanding of these intrinsic cellular defenses might be usefully exploited. ..
  18. Javanbakht H, Yuan W, Yeung D, Song B, Diaz Griffero F, Li Y, et al. Characterization of TRIM5alpha trimerization and its contribution to human immunodeficiency virus capsid binding. Virology. 2006;353:234-46 pubmed
    The coiled-coil domain of the tripartite motif (TRIM) family protein TRIM5alpha is required for trimerization and function as an antiretroviral restriction factor...
  19. Song B, Javanbakht H, Perron M, Park D, Stremlau M, Sodroski J. Retrovirus restriction by TRIM5alpha variants from Old World and New World primates. J Virol. 2005;79:3930-7 pubmed
    The TRIM5alpha proteins of humans and some Old World monkeys have been shown to block infection of particular retroviruses following virus entry into the host cell...
  20. Perez Caballero D, Hatziioannou T, Yang A, Cowan S, Bieniasz P. Human tripartite motif 5alpha domains responsible for retrovirus restriction activity and specificity. J Virol. 2005;79:8969-78 pubmed
    The tripartite motif 5alpha protein (TRIM5alpha) is one of several factors expressed by mammalian cells that inhibit retrovirus replication...
  21. Anderson J, Campbell E, Wu X, Vandegraaff N, Engelman A, Hope T. Proteasome inhibition reveals that a functional preintegration complex intermediate can be generated during restriction by diverse TRIM5 proteins. J Virol. 2006;80:9754-60 pubmed
    ..We recently found that proteasome inhibitors altered the rhesus monkey TRIM5alpha restriction of human immunodeficiency virus type 1 (HIV-1), allowing reverse transcription products to ..
  22. Ovsyannikova I, Dhiman N, Haralambieva I, Vierkant R, O Byrne M, Jacobson R, et al. Rubella vaccine-induced cellular immunity: evidence of associations with polymorphisms in the Toll-like, vitamin A and D receptors, and innate immune response genes. Hum Genet. 2010;127:207-21 pubmed publisher
    ..This is the first paper to present evidence that polymorphisms in the TLR, vitamin A, vitamin D receptor, and innate immunity genes can influence adaptive cytokine responses to rubella vaccination. ..
  23. Lienlaf M, Hayashi F, Di Nunzio F, Tochio N, Kigawa T, Yokoyama S, et al. Contribution of E3-ubiquitin ligase activity to HIV-1 restriction by TRIM5alpha(rh): structure of the RING domain of TRIM5alpha. J Virol. 2011;85:8725-37 pubmed publisher
    ..Remarkably, all of these changes were in residues located in the E2-binding region of the RING domain. Overall, these results demonstrate a role for TRIM5? self-ubiquitylation in the ability of TRIM5? to restrict HIV-1...
  24. Kamada K, Yamashita T, Hatcho K, Adachi A, Nomaguchi M. Evasion from CypA- and APOBEC-mediated restrictions is insufficient for HIV-1 to efficiently grow in simian cells. Microbes Infect. 2009;11:164-71 pubmed publisher
    ..Consistently, any of the HIV-1 variants examined here did not effectively counter CyM TRIM5alpha as judged by single-cycle infectivity assays...
  25. Sokolskaja E, Berthoux L, Luban J. Cyclophilin A and TRIM5alpha independently regulate human immunodeficiency virus type 1 infectivity in human cells. J Virol. 2006;80:2855-62 pubmed
    ..or African green monkey cells, where, paradoxically, the interaction decreases HIV-1 infectivity by facilitating TRIM5alpha-mediated restriction...
  26. Kutluay S, Perez Caballero D, Bieniasz P. Fates of retroviral core components during unrestricted and TRIM5-restricted infection. PLoS Pathog. 2013;9:e1003214 pubmed publisher
    ..Together, our results show how TRIM5? affects various retroviral core components and indicate that proteasomes are required for TRIM5?-induced core disruption but not for TRIM5?-induced restriction. ..
  27. Uchil P, Quinlan B, Chan W, Luna J, Mothes W. TRIM E3 ligases interfere with early and late stages of the retroviral life cycle. PLoS Pathog. 2008;4:e16 pubmed publisher
    ..In contrast, downregulation of TRIM11 and 15 enhanced virus release suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. ..
  28. Maegawa H, Nakayama E, Kuroishi A, Shioda T. Silencing of tripartite motif protein (TRIM) 5alpha mediated anti-HIV-1 activity by truncated mutant of TRIM5alpha. J Virol Methods. 2008;151:249-56 pubmed publisher
    ..It was found that both naturally occurring and artificial TRIM5alpha variants lacking the SPRY domain could silence TRIM5alpha activity...
  29. Sebastian S, Luban J. TRIM5alpha selectively binds a restriction-sensitive retroviral capsid. Retrovirology. 2005;2:40 pubmed
    ..Here we show that TRIM5alpha binds retroviral CA from detergent-stripped virions in a SPRY-dependent manner with sufficient discrimination to ..
  30. Sastri J, Campbell E. Recent insights into the mechanism and consequences of TRIM5? retroviral restriction. AIDS Res Hum Retroviruses. 2011;27:231-8 pubmed publisher
    ..We also discuss how polymorphisms within human and rhesus macaque populations have been demonstrated to affect disease progression of immunodeficiency viruses in these species. ..
  31. Javanbakht H, An P, Gold B, Petersen D, O hUigin C, Nelson G, et al. Effects of human TRIM5alpha polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection. Virology. 2006;354:15-27 pubmed
    b>TRIM5alpha acts on several retroviruses, including human immunodeficiency virus (HIV-1), to restrict cross-species transmission...
  32. Ohkura S, Stoye J. A comparison of murine leukemia viruses that escape from human and rhesus macaque TRIM5?s. J Virol. 2013;87:6455-68 pubmed publisher
  33. Hatziioannou T, Perez Caballero D, Yang A, Cowan S, Bieniasz P. Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5alpha. Proc Natl Acad Sci U S A. 2004;101:10774-9 pubmed
    ..susceptibility factor 1 and Ref1 are species-specific variants of tripartite interaction motif 5alpha (TRIM5alpha), a cytoplasmic body component recently shown to block HIV-1 infection in rhesus macaque cells, and can indeed ..
  34. Li X, Sodroski J. The TRIM5alpha B-box 2 domain promotes cooperative binding to the retroviral capsid by mediating higher-order self-association. J Virol. 2008;82:11495-502 pubmed publisher
    The retroviral restriction factor, TRIM5alpha, blocks infection of a spectrum of retroviruses soon after virus entry into the cell. TRIM5alpha consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains...
  35. Nakayama E, Carpentier W, Costagliola D, Shioda T, Iwamoto A, Debre P, et al. Wild type and H43Y variant of human TRIM5alpha show similar anti-human immunodeficiency virus type 1 activity both in vivo and in vitro. Immunogenetics. 2007;59:511-5 pubmed
    ..Recently, tripartite motif 5alpha (TRIM5alpha) was identified as a factor that confers resistance to HIV-1 infection in Old World monkey cells...
  36. Nakayama E, Shioda T. TRIM5? and Species Tropism of HIV/SIV. Front Microbiol. 2012;3:13 pubmed publisher
    ..As different TRIM5 genotypes of Rh showed different levels of simian immunodeficiency virus replication in vivo, the TRIM5 genotyping is thought to be important in acquired immunodeficiency syndrome monkey models. ..
  37. Arhel N. Revisiting HIV-1 uncoating. Retrovirology. 2010;7:96 pubmed publisher
  38. Shi J, Zhou J, Shah V, Aiken C, Whitby K. Small-molecule inhibition of human immunodeficiency virus type 1 infection by virus capsid destabilization. J Virol. 2011;85:542-9 pubmed publisher
    ..This study highlights uncoating as a step in the HIV-1 life cycle that is susceptible to small molecule intervention. ..
  39. Neil S, Bieniasz P. Human immunodeficiency virus, restriction factors, and interferon. J Interferon Cytokine Res. 2009;29:569-80 pubmed publisher
    ..Such knowledge could allow for novel forms of therapeutic intervention in pathogenic retroviral infections, as well as the development of animal models of human disease. ..
  40. Lin T, Emerman M. Determinants of cyclophilin A-dependent TRIM5 alpha restriction against HIV-1. Virology. 2008;379:335-41 pubmed publisher
    ..Moreover, we find that CypA/CA interaction occurs early after viral entry but the CypA-enhanced restriction mostly acts on the stage after reverse transcription. ..
  41. Carthagena L, Parise M, Ringeard M, Chelbi Alix M, Hazan U, Nisole S. Implication of TRIM alpha and TRIMCyp in interferon-induced anti-retroviral restriction activities. Retrovirology. 2008;5:59 pubmed publisher
    ..Furthermore, we found that type I IFN also induces a TRIMCyp-independent restriction activity specific to MLV in owl monkey cells. ..
  42. Shi J, Aiken C. Saturation of TRIM5 alpha-mediated restriction of HIV-1 infection depends on the stability of the incoming viral capsid. Virology. 2006;350:493-500 pubmed
    ..The results strongly suggest that the mechanism of HIV-1 restriction by TRIM5 alpha involves engagement of the viral capsid by the restriction factor prior to completion of uncoating. ..
  43. Rold C, Aiken C. Proteasomal degradation of TRIM5alpha during retrovirus restriction. PLoS Pathog. 2008;4:e1000074 pubmed publisher
    The host protein TRIM5alpha inhibits retroviral infection at an early post-penetration stage by targeting the incoming viral capsid...
  44. Diaz Griffero F, Qin X, Hayashi F, Kigawa T, Finzi A, Sarnak Z, et al. A B-box 2 surface patch important for TRIM5alpha self-association, capsid binding avidity, and retrovirus restriction. J Virol. 2009;83:10737-51 pubmed publisher
    b>TRIM5alpha is a tripartite motif (TRIM) protein that consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains...
  45. O CONNOR C, Pertel T, Gray S, Robia S, Bakowska J, Luban J, et al. p62/sequestosome-1 associates with and sustains the expression of retroviral restriction factor TRIM5alpha. J Virol. 2010;84:5997-6006 pubmed publisher
    ..proteins mediate a potent block to the cross-species transmission of retroviruses, the most well known being the TRIM5alpha protein from rhesus macaques, which potently inhibits human immunodeficiency virus type 1 (HIV-1) infection...
  46. Kratovac Z, Virgen C, Bibollet Ruche F, Hahn B, Bieniasz P, Hatziioannou T. Primate lentivirus capsid sensitivity to TRIM5 proteins. J Virol. 2008;82:6772-7 pubmed publisher
    ..b>TRIM5alpha proteins from other primates exhibited distinct restriction specificities for primate lentivirus capsids...
  47. Ganser Pornillos B, Chandrasekaran V, Pornillos O, Sodroski J, Sundquist W, Yeager M. Hexagonal assembly of a restricting TRIM5alpha protein. Proc Natl Acad Sci U S A. 2011;108:534-9 pubmed publisher
    ..Capsid recognition therefore involves a synergistic combination of direct binding interactions, avidity effects, templated assembly, and lattice complementarity...
  48. Li X, Li Y, Stremlau M, Yuan W, Song B, Perron M, et al. Functional replacement of the RING, B-box 2, and coiled-coil domains of tripartite motif 5alpha (TRIM5alpha) by heterologous TRIM domains. J Virol. 2006;80:6198-206 pubmed
    Tripartite motif 5alpha (TRIM5alpha) restricts some retroviruses, including human immunodeficiency virus type 1 (HIV-1), from infecting the cells of particular species...
  49. Diaz Griffero F, Perron M, McGee Estrada K, Hanna R, Maillard P, Trono D, et al. A human TRIM5alpha B30.2/SPRY domain mutant gains the ability to restrict and prematurely uncoat B-tropic murine leukemia virus. Virology. 2008;378:233-42 pubmed publisher
    Human TRIM5alpha restricts N-tropic murine leukemia virus (N-MLV) but not B-tropic MLV (B-MLV) infection. Here we study B30...
  50. Luban J. Cyclophilin A, TRIM5, and resistance to human immunodeficiency virus type 1 infection. J Virol. 2007;81:1054-61 pubmed
  51. Chatterji U, Bobardt M, Gaskill P, Sheeter D, Fox H, Gallay P. Trim5alpha accelerates degradation of cytosolic capsid associated with productive HIV-1 entry. J Biol Chem. 2006;281:37025-33 pubmed
    The TRIM5alpha (tripartite motif 5alpha protein) has been linked to the cross-species restriction in human immunodeficiency virus type 1 (HIV-1) infection of non-human cells, but the mechanism by which this occurs remains to be fully ..
  52. Li X, Gold B, O hUigin C, Diaz Griffero F, Song B, Si Z, et al. Unique features of TRIM5alpha among closely related human TRIM family members. Virology. 2007;360:419-33 pubmed
    The tripartite motif (TRIM) protein, TRIM5alpha, restricts some retroviruses, including human immunodeficiency virus (HIV-1), from infecting the cells of particular species...
  53. Zhao G, Ke D, Vu T, Ahn J, Shah V, Yang R, et al. Rhesus TRIM5? disrupts the HIV-1 capsid at the inter-hexamer interfaces. PLoS Pathog. 2011;7:e1002009 pubmed publisher
  54. Berthoux L, Sebastian S, Sayah D, Luban J. Disruption of human TRIM5alpha antiviral activity by nonhuman primate orthologues. J Virol. 2005;79:7883-8 pubmed
    ..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)...
  55. Yamauchi K, Wada K, Tanji K, Tanaka M, Kamitani T. Ubiquitination of E3 ubiquitin ligase TRIM5 alpha and its potential role. FEBS J. 2008;275:1540-55 pubmed publisher
    ..Here, we show that TRIM5alpha functions as a RING-finger-type E3 ubiquitin ligase both in vitro and in vivo and ubiquitinates itself in ..
  56. Sawyer S, Wu L, Akey J, Emerman M, Malik H. High-frequency persistence of an impaired allele of the retroviral defense gene TRIM5alpha in humans. Curr Biol. 2006;16:95-100 pubmed
    The intracellular TRIM5alpha protein successfully inhibits HIV-1 infection in rhesus monkeys, but not in humans ...
  57. 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;101:10780-5 pubmed
    The rhesus macaque tripartite motif containing protein TRIM5alpha specifically restricts HIV-1 infection at an early post-entry step before reverse transcription [Stremlau, M., Owens, C. M., Perron, M. J., Kiessling, M., Autissier, P...
  58. Sebastian S, Grütter C, Strambio de Castillia C, Pertel T, Olivari S, Grutter M, et al. An invariant surface patch on the TRIM5alpha PRYSPRY domain is required for retroviral restriction but dispensable for capsid binding. J Virol. 2009;83:3365-73 pubmed publisher
    b>TRIM5alpha is a retrovirus restriction factor in the host cell cytoplasm that blocks infection before provirus establishment. Restriction activity requires capsid (CA)-specific recognition by the PRYSPRY domain of TRIM5alpha...
  59. Ohkura S, Goldstone D, Yap M, Holden Dye K, Taylor I, Stoye J. Novel escape mutants suggest an extensive TRIM5? binding site spanning the entire outer surface of the murine leukemia virus capsid protein. PLoS Pathog. 2011;7:e1002011 pubmed publisher
    ..We conclude that interactions involving much, if not all, of the surface of CA are vital for TRIM5? binding. ..
  60. Diaz Griffero F, Kar A, Perron M, Xiang S, Javanbakht H, Li X, et al. Modulation of retroviral restriction and proteasome inhibitor-resistant turnover by changes in the TRIM5alpha B-box 2 domain. J Virol. 2007;81:10362-78 pubmed
    An intact B-box 2 domain is essential for the antiretroviral activity of TRIM5alpha. We modeled the structure of the B-box 2 domain of TRIM5alpha based on the existing three-dimensional structure of the B-box 2 domain of human TRIM29...
  61. Battivelli E, Migraine J, Lecossier D, Yeni P, Clavel F, Hance A. Gag cytotoxic T lymphocyte escape mutations can increase sensitivity of HIV-1 to human TRIM5alpha, linking intrinsic and acquired immunity. J Virol. 2011;85:11846-54 pubmed publisher
    ..Taken together, these findings suggest that CTL mutations may influence HIV-1 replication by modifying both viral infectivity and sensitivity to TRIM5?. ..
  62. Diaz Griffero F, Gallo D, Hope T, Sodroski J. Trafficking of some old world primate TRIM5? proteins through the nucleus. Retrovirology. 2011;8:38 pubmed publisher
    ..We discovered the ability of human and rhesus TRIM5? to shuttle into and out of the nucleus. This novel trafficking ability of TRIM5? proteins could be important for an as-yet-unknown function of TRIM5?. ..
  63. Woo J, Imm J, Min C, Kim K, Cha S, Oh B. Structural and functional insights into the B30.2/SPRY domain. EMBO J. 2006;25:1353-63 pubmed
    ..approximately 700 eukaryotic (approximately 150 human) proteins, including medically important proteins such as TRIM5alpha and Pyrin. Nonetheless, the functional role of this modular domain remained unclear...
  64. Stremlau M, Song B, Javanbakht H, Perron M, Sodroski J. Cyclophilin A: an auxiliary but not necessary cofactor for TRIM5alpha restriction of HIV-1. Virology. 2006;351:112-20 pubmed
    ..The retroviral restriction factor TRIM5alpha can inhibit the early, post-entry phase of infection by associating with the incoming viral capsid...
  65. Grutter M, Luban J. TRIM5 structure, HIV-1 capsid recognition, and innate immune signaling. Curr Opin Virol. 2012;2:142-50 pubmed publisher
    ..Structural and biochemical studies on TRIM5 have opened a much needed window on how the innate immune system detects the distinct molecular features of HIV-1 and other retroviruses...
  66. Price H, Lacap P, Tuff J, Wachihi C, Kimani J, Ball T, et al. A TRIM5alpha exon 2 polymorphism is associated with protection from HIV-1 infection in the Pumwani sex worker cohort. AIDS. 2010;24:1813-21 pubmed publisher
    The innate immune component TRIM5alpha has the ability to restrict retrovirus infection in a species-specific manner. TRIM5alpha of some primate species restricts infection by HIV-1, whereas human TRIM5alpha lacks this specificity...
  67. Schaller T, Hue S, Towers G. An active TRIM5 protein in rabbits indicates a common antiviral ancestor for mammalian TRIM5 proteins. J Virol. 2007;81:11713-21 pubmed
    ..Restriction is species specific. For example, TRIM5alpha from Old World monkeys, but not humans, restricts human immunodeficiency virus type 1 infection...
  68. Nakayama E, Shingai Y, Kono K, Shioda T. TRIM5alpha-independent anti-human immunodeficiency virus type 1 activity mediated by cyclophilin A in Old World monkey cells. Virology. 2008;375:514-20 pubmed publisher
    ..b>TRIM5alpha is an antiretroviral factor influencing species-specific retroviral replication in Old World monkey (OWM) cells...
  69. Nakajima T, Nakayama E, Kaur G, Terunuma H, Mimaya J, Ohtani H, et al. Impact of novel TRIM5alpha variants, Gly110Arg and G176del, on the anti-HIV-1 activity and the susceptibility to HIV-1 infection. AIDS. 2009;23:2091-100 pubmed publisher
    b>TRIM5alpha is one of the factors contributing to intracellular defense mechanisms against HIV-1 infection. We investigated the association of TRIM5alpha sequence variations with the susceptibility to HIV-1 infection in Japanese and Indian...
  70. Stremlau M, Perron M, Welikala S, Sodroski J. Species-specific variation in the B30.2(SPRY) domain of TRIM5alpha determines the potency of human immunodeficiency virus restriction. J Virol. 2005;79:3139-45 pubmed
    ..Human immunodeficiency virus type 1 (HIV-1) is blocked in the cells of Old World monkeys by TRIM5alpha, a tripartite motif (TRIM) protein composed of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains...
  71. Yap M, Nisole S, Stoye J. A single amino acid change in the SPRY domain of human Trim5alpha leads to HIV-1 restriction. Curr Biol. 2005;15:73-8 pubmed
    ..Recently, it has become clear that Ref1 and Lv1 are encoded by the same gene, Trim5alpha, which inhibits retrovirus replication in a species-specific manner...
  72. Ohkura S, Yap M, Sheldon T, Stoye J. All three variable regions of the TRIM5alpha B30.2 domain can contribute to the specificity of retrovirus restriction. J Virol. 2006;80:8554-65 pubmed
    Recent studies have revealed the contribution of TRIM5alpha to retrovirus restriction in cells from a variety of primate species. TRIM5alpha consists of a tripartite motif (the RBCC domain) followed by a B30.2 domain. The B30...
  73. 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. 2007;81:2138-48 pubmed
    The host cell factors TRIM5alpha(hu) and Fv-1 restrict N-tropic murine leukemia virus (N-MLV) infection at an early postentry step before or after reverse transcription, respectively...
  74. Malim M, Bieniasz P. HIV Restriction Factors and Mechanisms of Evasion. Cold Spring Harb Perspect Med. 2012;2:a006940 pubmed publisher
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    ..can markedly reduce viral fitness, and interactions of CA with host proteins such as cyclophilin A (CypA) and TRIM5alpha can have important effects on viral infectivity...
  77. Perron M, Stremlau M, Song B, Ulm W, Mulligan R, Sodroski J. TRIM5alpha mediates the postentry block to N-tropic murine leukemia viruses in human cells. Proc Natl Acad Sci U S A. 2004;101:11827-32 pubmed
    ..A similar block to HIV-1 in rhesus monkey cells is mediated by TRIM5alpha. Here we show that human TRIM5alpha is both necessary and sufficient for the restriction of N-MLV in human cells...
  78. Passerini L, Keckesova Z, Towers G. Retroviral restriction factors Fv1 and TRIM5alpha act independently and can compete for incoming virus before reverse transcription. J Virol. 2006;80:2100-5 pubmed
    The restriction factors Fv1 and TRIM5alpha provide dominant blocks to retroviral infection, targeting incoming capsids at a postentry, preintegration step...
  79. Pacheco B, Finzi A, Stremlau M, Sodroski J. Adaptation of HIV-1 to cells expressing rhesus monkey TRIM5?. Virology. 2010;408:204-12 pubmed publisher
    ..Thus, a preferred HIV-1 escape pathway involves decreased binding to TRIM5?, a capsid-destabilizing factor, and retention of binding to cyclophilin A, a capsid-stabilizing factor. ..
  80. Kaiser S, Malik H, Emerman M. Restriction of an extinct retrovirus by the human TRIM5alpha antiviral protein. Science. 2007;316:1756-8 pubmed
    ..endogenous virus from the chimpanzee genome and show that the human variant of the intrinsic immune protein TRIM5alpha can actively prevent infection by this virus...
  81. Arriagada G, Muntean L, Goff S. SUMO-interacting motifs of human TRIM5? are important for antiviral activity. PLoS Pathog. 2011;7:e1002019 pubmed publisher
    ..We propose that at least a portion of the antiviral activity of TRIM5? is mediated through the binding of its SIMs to SUMO-conjugated CA. ..
  82. Yap M, Nisole S, Lynch C, Stoye J. Trim5alpha protein restricts both HIV-1 and murine leukemia virus. Proc Natl Acad Sci U S A. 2004;101:10786-91 pubmed
    ..Recently, Trim5alpha protein from rhesus monkey was found to restrict HIV-1...
  83. Xu L, Yang L, Moitra P, Hashimoto K, Rallabhandi P, Kaul S, et al. BTBD1 and BTBD2 colocalize to cytoplasmic bodies with the RBCC/tripartite motif protein, TRIM5delta. Exp Cell Res. 2003;288:84-93 pubmed
    ..Thus, four protein modules found on each of these putative ubiquitin ligases, a RING, a B-box and two PHR repeats, are present on BTBD1/2 and TRIM5delta that are colocalized to cytoplasmic bodies. ..
  84. Takeuchi J, Perche B, Migraine J, Mercier Delarue S, Ponscarme D, Simon F, et al. High level of susceptibility to human TRIM5? conferred by HIV-2 capsid sequences. Retrovirology. 2013;10:50 pubmed publisher
    ..HIV-2 capsid sequences expressed high levels of susceptibility to hTRIM5?. This property, common to all HIV-2 sequences tested, may contribute in part to the lower replication and pathogenicity of this virus in humans. ..
  85. Luban J. TRIM5 and the Regulation of HIV-1 Infectivity. Mol Biol Int. 2012;2012:426840 pubmed publisher
    ..Better understanding of the complex interaction between TRIM5 and the retrovirus capsid lattice may someday lead to exploitation of this interaction for the development of potent HIV-1 inhibitors. ..
  86. Liu F, Qiu Y, Li H, Kuang Y, Tang X, Cao G, et al. An HIV-1 resistance polymorphism in TRIM5? gene among Chinese intravenous drug users. J Acquir Immune Defic Syndr. 2011;56:306-11 pubmed publisher
    ..46 (0.22 to 0.94), P = 0.033, Mantel-Haenszel test]. we concluded that H43Y might account for the HIV-1 resistance due to TRIM5? gene in Chinese IDUs. ..
  87. Huthoff H, Towers G. Restriction of retroviral replication by APOBEC3G/F and TRIM5alpha. Trends Microbiol. 2008;16:612-9 pubmed publisher
    ..Examples of such molecules are APOBEC3G, APOBEC3F and TRIM5alpha. APOBEC3G and APOBEC3F are cytidine deaminases that are able to strongly inhibit retroviral replication by at ..
  88. Stremlau M, Owens C, Perron M, Kiessling M, Autissier P, Sodroski J. The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys. Nature. 2004;427:848-53 pubmed
    ..Here we identify TRIM5alpha, a component of cytoplasmic bodies, as the blocking factor...