TRIM5

Summary

Gene Symbol: TRIM5
Description: tripartite motif containing 5
Alias: tripartite motif-containing protein 5, RING-type E3 ubiquitin transferase TRIM5, TRIM5alpha, tripartite motif-containing 5 alpha isoform, tripartite motif-containing 5/cyclophilin A fusion protein, tripartite motif-containing protein 5 isoform alpha
Species: Rhesus monkey
Products:     TRIM5

Top Publications

  1. Biris N, Yang Y, Taylor A, Tomashevski A, Guo M, Hart P, et al. Structure of the rhesus monkey TRIM5? PRYSPRY domain, the HIV capsid recognition module. Proc Natl Acad Sci U S A. 2012;109:13278-83 pubmed publisher
    Tripartite motif protein TRIM5? blocks retroviral replication after cell entry, and species-specific differences in its activity are determined by sequence variations within the C-terminal B30.2/PRYSPRY domain...
  2. Reynolds M, Sacha J, Weiler A, Borchardt G, Glidden C, Sheppard N, et al. The TRIM5{alpha} genotype of rhesus macaques affects acquisition of simian immunodeficiency virus SIVsmE660 infection after repeated limiting-dose intrarectal challenge. J Virol. 2011;85:9637-40 pubmed publisher
    It has recently been shown that polymorphism at the rhesus macaque TRIM5 locus can affect simian immunodeficiency virus (SIV) replication. Here we show that TRIM5 alleles can also affect acquisition of SIVsmE660...
  3. 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...
  4. Lim S, Rogers T, Chan T, Whitney J, Kim J, Sodroski J, et al. TRIM5alpha Modulates Immunodeficiency Virus Control in Rhesus Monkeys. PLoS Pathog. 2010;6:e1000738 pubmed publisher
    The cytoplasmic TRIM5alpha proteins of certain mammalian lineages efficiently recognize the incoming capsids of particular retroviruses and potently restrict infection in a species-specific manner...
  5. Reszka N, Zhou C, Song B, Sodroski J, Knipe D. Simian TRIM5alpha proteins reduce replication of herpes simplex virus. Virology. 2010;398:243-50 pubmed publisher
    Old World monkey TRIM5alpha proteins are known to block the replication of human immunodeficiency virus and other retroviruses in a species-specific fashion...
  6. 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...
  7. Brandariz Nuñez A, Roa A, Valle Casuso J, Biris N, Ivanov D, Diaz Griffero F. Contribution of SUMO-interacting motifs and SUMOylation to the antiretroviral properties of TRIM5?. Virology. 2013;435:463-71 pubmed publisher
    Recent findings suggested that the SUMO-interacting motifs (SIMs) present in the human TRIM5? (TRIM5?(hu)) protein play an important role in the ability of TRIM5?(hu) to restrict N-MLV...
  8. Yang H, Ji X, Zhao G, Ning J, Zhao Q, Aiken C, et al. Structural insight into HIV-1 capsid recognition by rhesus TRIM5?. Proc Natl Acad Sci U S A. 2012;109:18372-7 pubmed publisher
    Tripartite motif protein isoform 5 alpha (TRIM5?) is a potent antiviral protein that restricts infection by HIV-1 and other retroviruses. TRIM5? recognizes the lattice of the retrovirus capsid through its B30...
  9. 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;13:631-5 pubmed
    ..Tripartite motif-containing 5 isoform-alpha (TRIM5alpha) protein from rhesus monkey (TRIM5alpharh) restricts human immunodeficiency virus type 1 (HIV-1) infection at a ..

More Information

Publications57

  1. 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
    ..This virus (NL-4/5S6/7SvifS) was supposed to escape from host restriction factors cyclophilin A, CM TRIM5 alpha, and APOBEC3G. However, the replicative capability of NL-4/5S6/7SvifS in human cells was severely impaired...
  2. Kirmaier A, Wu F, Newman R, Hall L, Morgan J, O Connor S, et al. TRIM5 suppresses cross-species transmission of a primate immunodeficiency virus and selects for emergence of resistant variants in the new species. PLoS Biol. 2010;8: pubmed publisher
    ..Cellular assays and phylogenetic comparisons indirectly support a role for TRIM5alpha, the product of the TRIM5 gene, in suppressing interspecies transmission and emergence of retroviruses in nature...
  3. 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
    ..Rhesus macaque TRIM5? (TRIM5?(rh)) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse ..
  4. 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
    To better understand the binding mechanism of TRIM5? to retrovirus capsid, we had previously selected N-tropic murine leukemia virus (N-MLV) mutants escaping from rhesus macaque TRIM5? (rhTRIM5?) by passaging the virus in rhTRIM5?-..
  5. Campbell E, Perez O, Anderson J, Hope T. Visualization of a proteasome-independent intermediate during restriction of HIV-1 by rhesus TRIM5alpha. J Cell Biol. 2008;180:549-61 pubmed publisher
    ..b>TRIM5alpha restricts retroviral infection early after viral entry, before the generation of viral reverse transcription ..
  6. 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...
  7. 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...
  8. Li X, Yeung D, Fiegen A, Sodroski J. Determinants of the higher order association of the restriction factor TRIM5alpha and other tripartite motif (TRIM) proteins. J Biol Chem. 2011;286:27959-70 pubmed publisher
    ..For example, dimers of TRIM5?, a host factor that restricts retrovirus infection, assemble into higher order arrays on the surface of the viral ..
  9. Liu H, Wang Y, Liao C, Kuang Y, Zheng Y, Su B. Adaptive evolution of primate TRIM5alpha, a gene restricting HIV-1 infection. Gene. 2005;362:109-16 pubmed publisher
    Recent studies showed that nonhuman primate TRIM5alpha can efficiently block HIV-1 infection in human cell lines. It can also restrict other retroviruses, therefore, suggested as a general defender against retrovirus infection...
  10. Newman R, Hall L, Connole M, Chen G, Sato S, Yuste E, et al. Balancing selection and the evolution of functional polymorphism in Old World monkey TRIM5alpha. Proc Natl Acad Sci U S A. 2006;103:19134-9 pubmed
    Retroviral restriction factor TRIM5alpha exhibits a high degree of sequence variation among primate species. It has been proposed that this diversity is the cumulative result of ancient, lineage-specific episodes of positive selection...
  11. 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
    b>TRIM5? and TRIMCyp are cytoplasmic proteins that bind incoming retroviral capsids and mediate early blocks to viral infection. TRIM5 proteins form cytoplasmic bodies, which are highly dynamic structures...
  12. 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
    ..For example, the TRIM5? proteins of Old World monkeys block the early, post-entry steps in human immunodeficiency virus (HIV-1) infection...
  13. 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...
  14. Yeh W, Rao S, Lim S, Zhang J, Hraber P, Brassard L, et al. The TRIM5 gene modulates penile mucosal acquisition of simian immunodeficiency virus in rhesus monkeys. J Virol. 2011;85:10389-98 pubmed publisher
    ..In addition to serving as a block for cross-species retroviral infection, TRIM5 was recently shown to play a central role in limiting primate immunodeficiency virus replication...
  15. Wilson S, Webb B, Ylinen L, Verschoor E, Heeney J, Towers G. Independent evolution of an antiviral TRIMCyp in rhesus macaques. Proc Natl Acad Sci U S A. 2008;105:3557-62 pubmed publisher
    The antiretroviral restriction factor TRIM5 has recently emerged as an important mediator of innate immunity and species-specific inhibition of retroviral replication in mammals...
  16. 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...
  17. Sakuma R, Ohmine S, Ikeda Y. Determinants for the rhesus monkey TRIM5alpha-mediated block of the late phase of HIV-1 replication. J Biol Chem. 2010;285:3784-93 pubmed publisher
    Rhesus monkey TRIM5alpha (TRIM5alpharh) includes RING, B-box, coiled-coil, and B30.2(PRYSPRY) domains and blocks HIV-1 infection by targeting HIV-1 core through a B30.2(PRYSPRY) domain...
  18. Hwang C, Holl J, Rajan D, Lee Y, Kim S, Um M, et al. Hsp70 interacts with the retroviral restriction factor TRIM5alpha and assists the folding of TRIM5alpha. J Biol Chem. 2010;285:7827-37 pubmed publisher
    Tripartite motif (TRIM) protein TRIM5alpha has been shown to restrict human immunodeficiency virus, type 1 infection in Old World monkey cells at the early post-entry step by poorly understood mechanisms...
  19. Nepveu Traversy M, Berthoux L. The conserved sumoylation consensus site in TRIM5? modulates its immune activation functions. Virus Res. 2014;184:30-8 pubmed publisher
    b>TRIM5? is a type I interferon-stimulated anti-retroviral restriction factor expressed in most primates and homologous proteins are expressed in other mammals. Through its C-terminal PRYSPRY (B30...
  20. Dutrieux J, Portilho D, Arhel N, Hazan U, Nisole S. TRIM5α is a SUMO substrate. Retrovirology. 2015;12:28 pubmed publisher
    The TRIM5α restriction factor interferes with retroviral infections by inhibiting an early step of viral replication...
  21. Wang X, Yu Q, Yuan Y, Teng Z, Li D, Zeng Y. Targeting the rhesus macaque TRIM5? gene to enhance the susceptibility of CD4+ T cells to HIV-1 infection. Arch Virol. 2017;162:793-798 pubmed publisher
    ..The species-specific innate immune factor tripartite motif 5 alpha (TRIM5?) is a key molecule that confers potent resistance against HIV-1 infection...
  22. Soll S, Wilson S, Kutluay S, Hatziioannou T, Bieniasz P. Assisted evolution enables HIV-1 to overcome a high TRIM5α-imposed genetic barrier to rhesus macaque tropism. PLoS Pathog. 2013;9:e1003667 pubmed publisher
    ..Indeed, rhesus macaques are resistant to HIV-1, in part due to restriction imposed by the TRIM5α protein (rhTRIM5α)...
  23. Ohmine S, Sakuma R, Sakuma T, Thatava T, Solis G, Ikeda Y. Cytoplasmic body component TRIM5{alpha} requires lipid-enriched microdomains for efficient HIV-1 restriction. J Biol Chem. 2010;285:34508-17 pubmed publisher
    b>TRIM5? is a member of the tripartite motif (TRIM) family of proteins and affects both early and late phases of the retroviral life cycle...
  24. Butler K, Morgan J, Hanson D, Adams D, Garcia Lerma J, Heneine W, et al. Susceptibility to repeated, low-dose, rectal SHIVSF162P3 challenge is independent of TRIM5 genotype in rhesus macaques. AIDS Res Hum Retroviruses. 2013;29:1091-4 pubmed publisher
    ..Different susceptibilities among animals can complicate study designs. In rhesus macaques, TRIM5 alleles Q, CypA, and TFP are resistance factors for infection with some S(H)IV strains, but not for SIVmac239 due ..
  25. Keown J, Goldstone D. Crystal structure of the Trim5α Bbox2 domain from rhesus macaques describes a plastic oligomerisation interface. J Struct Biol. 2016;195:282-285 pubmed publisher
    ..One such antiretroviral protein is the restriction factor Trim5α, that blocks HIV-1 infection in rhesus macaques at an early post-entry stage in the retroviral lifecycle...
  26. 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
    b>TRIM5?(rh) is a cytosolic protein that potently restricts HIV-1 before reverse transcription. TRIM5?(rh) is composed of four different domains: RING, B-box 2, coiled coil, and B30.2(SPRY)...
  27. Danielson C, Cianci G, Hope T. Recruitment and dynamics of proteasome association with rhTRIM5? cytoplasmic complexes during HIV-1 infection. Traffic. 2012;13:1206-17 pubmed publisher
    ..One such restriction factor is the rhesus macaque variant of TRIM5? (rhTRIM5?), which potently blocks infection by HIV-1...
  28. Yu C, Na L, Lv X, Liu J, Liu X, Ji F, et al. The TRIMCyp genotype in four species of macaques in China. Immunogenetics. 2013;65:185-93 pubmed publisher
    ..Taken together, the data in this study provide important information about the genomic background of TRIMCyp among major species of Chinese macaques. ..
  29. Lamichhane R, Mukherjee S, Smolin N, Pauszek R, Bradley M, Sastri J, et al. Dynamic conformational changes in the rhesus TRIM5? dimer dictate the potency of HIV-1 restriction. Virology. 2017;500:161-168 pubmed publisher
    The TRIM5? protein from rhesus macaques (rhTRIM5?) mediates a potent inhibition of HIV-1 infection via a mechanism that involves the abortive disassembly of the viral core...
  30. Kar A, Mao Y, Bird G, WALENSKY L, Sodroski J. Characterization of a core fragment of the rhesus monkey TRIM5? protein. BMC Biochem. 2011;12:1 pubmed publisher
    Like all tripartite motif (TRIM) proteins, the retroviral restriction factor TRIM5? consists of RING, B-box 2 and coiled-coil domains, with a C-terminal B30.2(SPRY) domain...
  31. Campbell E, Weingart J, Sette P, Opp S, Sastri J, O Connor S, et al. TRIM5α-Mediated Ubiquitin Chain Conjugation Is Required for Inhibition of HIV-1 Reverse Transcription and Capsid Destabilization. J Virol. 2016;90:1849-57 pubmed publisher
    Rhesus macaque TRIM5α (rhTRIM5α) is a retroviral restriction factor that inhibits HIV-1 infection. Previous studies have revealed that TRIM5α restriction occurs via a two-step process...
  32. Goldstone D, Walker P, Calder L, Coombs P, Kirkpatrick J, Ball N, et al. Structural studies of postentry restriction factors reveal antiparallel dimers that enable avid binding to the HIV-1 capsid lattice. Proc Natl Acad Sci U S A. 2014;111:9609-14 pubmed publisher
    Restriction factors (RFs) form important components of host defenses to retroviral infection. The Fv1, Trim5?, and TrimCyp RFs contain N-terminal dimerization and C-terminal specificity domains that target assembled retroviral capsid (CA)..
  33. Richardson M, Guo L, Xin F, Yang X, Riley J. Stabilized human TRIM5? protects human T cells from HIV-1 infection. Mol Ther. 2014;22:1084-1095 pubmed publisher
    Rhesus (rh) but not human (hu) TRIM5? potently restricts human immunodeficiency virus (HIV)-1 infection. It is not clear why huTRIM5? fails to effectively block HIV infection, but it is thought to have a lower affinity for the viral core...
  34. Setiawan L, Kootstra N. Adaptation of HIV-1 to rhTrim5α-mediated restriction in vitro. Virology. 2015;486:239-47 pubmed publisher
    ..Therefore, gene therapy with rhTrim5α might be suitable for HIV-1 treatment, however the virus will eventually escape the pressure by gaining mutations in the conserved regions of the viral genome without any severe fitness cost. ..
  35. Li X, Kim J, Song B, Finzi A, Pacheco B, Sodroski J. Virus-specific effects of TRIM5?(rh) RING domain functions on restriction of retroviruses. J Virol. 2013;87:7234-45 pubmed publisher
    The tripartite motif protein TRIM5? restricts particular retrovirus infections by binding to the incoming capsid and inhibiting the early stage of virus infection...
  36. Gong J, Shen X, Qiu H, Chen C, Yang R. Rhesus monkey TRIM5? represses HIV-1 LTR promoter activity by negatively regulating TAK1/TAB1/TAB2/TAB3-complex-mediated NF-?B activation. Arch Virol. 2011;156:1997-2006 pubmed publisher
    b>TRIM5? has been identified as the main restriction factor responsible for resistance of Old World monkey cells to HIV-1 infection. The precise mechanism of viral inhibition by TRIM5? remains elusive but appears to occur in multiple ways...
  37. Anderson J. Using TRIM5? as an HIV therapeutic: the alpha gene?. Expert Opin Biol Ther. 2013;13:1029-38 pubmed publisher
    ..With the discovery of TRIM5?, an HIV inhibitor and species-specific restriction factor, a new molecule can be evaluated as an HIV gene ..
  38. Matsuda K, Dang Q, Brown C, Keele B, Wu F, Ourmanov I, et al. Characterization of simian immunodeficiency virus (SIV) that induces SIV encephalitis in rhesus macaques with high frequency: role of TRIM5 and major histocompatibility complex genotypes and early entry to the brain. J Virol. 2014;88:13201-11 pubmed publisher
    ..in the animals used in the study suggested that host major histocompatibility complex class I (MHC-I) and TRIM5α genotypes influence the disease progression in the CNS...
  39. Nomaguchi M, Nakayama E, Yokoyama M, Doi N, Igarashi T, Shioda T, et al. Distinct combinations of amino acid substitutions in N-terminal domain of Gag-capsid afford HIV-1 resistance to rhesus TRIM5α. Microbes Infect. 2014;16:936-44 pubmed publisher
    b>TRIM5α is a potent anti-retroviral factor that interacts with viral capsid (CA) in a species-specific manner...
  40. Wu F, Ourmanov I, Riddick N, Matsuda K, Whitted S, Plishka R, et al. TRIM5α restriction affects clinical outcome and disease progression in simian immunodeficiency virus-infected rhesus macaques. J Virol. 2015;89:2233-40 pubmed publisher
    Tripartite motif-containing protein 5α (TRIM5α) is considered to be a potential target for cell-based gene modification therapy against human immunodeficiency virus type 1 (HIV-1) infection...
  41. Roa A, Hayashi F, Yang Y, Lienlaf M, Zhou J, Shi J, et al. RING domain mutations uncouple TRIM5? restriction of HIV-1 from inhibition of reverse transcription and acceleration of uncoating. J Virol. 2012;86:1717-27 pubmed publisher
    Rhesus TRIM5? (TRIM5?(rh)) is a cytosolic protein that potently restricts HIV-1 at an early postentry stage, prior to reverse transcription...
  42. Sukegawa S, Sakuma R, Ohmine S, Takeuchi H, Ikeda Y, Yamaoka S. Suppressor of cytokine signaling 1 counteracts rhesus macaque TRIM5α-induced inhibition of human immunodeficiency virus type-1 production. PLoS ONE. 2014;9:e109640 pubmed publisher
    Old world monkey TRIM5α is a host factor that restricts human immunodeficiency virus type-1 (HIV-1) infection...
  43. Mandell M, Jain A, Arko Mensah J, Chauhan S, Kimura T, Dinkins C, et al. TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition. Dev Cell. 2014;30:394-409 pubmed publisher
    ..Furthermore, TRIM5? acts as a selective autophagy receptor...
  44. Wu F, Kirmaier A, Goeken R, Ourmanov I, Hall L, Morgan J, et al. TRIM5 alpha drives SIVsmm evolution in rhesus macaques. PLoS Pathog. 2013;9:e1003577 pubmed publisher
    ..the non-restrictive TRIM5? allele TRIM5(Q) was significantly higher than in macaques expressing two restrictive TRIM5alpha alleles TRIM5(TFP/TFP) or TRIM5(Cyp/TFP)...
  45. Danielson C, Hope T. Using antiubiquitin antibodies to probe the ubiquitination state within rhTRIM5? cytoplasmic bodies. AIDS Res Hum Retroviruses. 2013;29:1373-85 pubmed publisher
    ..Taken together, it is likely that rhTRIM5? cytoplasmic bodies are involved in recruiting components of the ubiquitin-proteasome system to coordinate proteasomal destruction of a viral or cellular protein(s) during restriction of HIV-1. ..
  46. Lukic Z, Goff S, Campbell E, Arriagada G. Role of SUMO-1 and SUMO interacting motifs in rhesus TRIM5?-mediated restriction. Retrovirology. 2013;10:10 pubmed publisher
    b>TRIM5? is a member of the tripartite motif family of proteins that restricts retroviral infection in a species-specific manner. The restriction requires an interaction between the viral capsid lattice and the B30.2/SPRY domain of TRIM5?...
  47. Yang Y, Brandariz Nu ez A, Fricke T, IVANOV D, Sarnak Z, Diaz Griffero F. Binding of the rhesus TRIM5? PRYSPRY domain to capsid is necessary but not sufficient for HIV-1 restriction. Virology. 2014;448:217-28 pubmed publisher
    The PRYSPRY domain of TRIM5? provides specificity and the capsid recognition motif to retroviral restriction...
  48. Lim S, Chan T, Gelman R, Whitney J, O Brien K, Barouch D, et al. Contributions of Mamu-A*01 status and TRIM5 allele expression, but not CCL3L copy number variation, to the control of SIVmac251 replication in Indian-origin rhesus monkeys. PLoS Genet. 2010;6:e1000997 pubmed publisher
    ..34 or 0.36, respectively. These findings call into question the premise that CCL3L CNV is important in HIV/SIV pathogenesis. ..