Skip to main content

Advertisement

SpringerLink
Log in

The retroviral restriction factor TRIM5α

  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Retroviruses are obligate intracellular parasites that have coevolved with their hosts for millions of years. It is therefore not surprising that retroviruses take advantage of numerous host factors during their life cycle. In addition to positive cellular factors that are of use to the virus, host cells have also evolved intracellular proteins to antagonize the retroviral replication cycle. Such inhibitory cellular factors have been called retroviral restriction factors. Recently, several such restriction factors have been cloned, including Friend virus susceptibility factor 1, apolipoprotein B mRNA-editing enzyme catalytic proteins 3F and 3G, and ZAP. Here, we review the explosion of publications from the past 2 years concerning TRIM5, a host factor that potently inhibits HIV-1 and other retroviruses.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Best S, Le Tissier P, Towers G, Stoye JP: Positional cloning of the mouse retrovirus restriction gene Fv1. Nature 1996, 382:826–829.

    Article  PubMed  CAS  Google Scholar 

  2. Sheehy AM, Gaddis NC, Choi JD, Malim MH: Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 2002, 418:646–650.

    Article  PubMed  CAS  Google Scholar 

  3. Zheng YH, Irwin D, Kurosu T, et al.: Human APOBEC3F is another host factor that blocks human immunodeficiency virus type 1 replication. J Virol 2004, 78:6073–6076.

    Article  PubMed  CAS  Google Scholar 

  4. Wiegand HL, Doehle BP, Bogerd HP, Cullen BR: A second human antiretroviral factor, APOBEC3F, is suppressed by the HIV-1 and HIV-2 Vif proteins. EMBO J 2004, 23:2451–2458.

    Article  PubMed  CAS  Google Scholar 

  5. Bishop KN, Holmes RK, Malim MH: Antiviral potency of APOBEC proteins does not correlate with cytidine deamination. J Virol 2006, 80:8450–8458.

    Article  PubMed  CAS  Google Scholar 

  6. Turelli P, Mangeat B, Jost S, et al.: Inhibition of hepatitis B virus replication by APOBEC3G. Science 2004, 303:1829.

    Article  PubMed  Google Scholar 

  7. Mariani R, Chen D, Schrofelbauer B, et al.: Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell 2003, 114:21–31.

    Article  PubMed  CAS  Google Scholar 

  8. Yu X, Yu Y, Liu B, et al.: Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science 2003, 302:1056–1060.

    Article  PubMed  CAS  Google Scholar 

  9. Gao G, Guo X, Goff SP: Inhibition of retroviral RNA production by ZAP, a CCCH-type zinc finger protein. Science 2002, 297:1703–1706.

    Article  PubMed  CAS  Google Scholar 

  10. Guo X, Carroll JW, Macdonald MR, et al.: The zinc finger antiviral protein directly binds to specific viral mRNAs through the CCCH zinc finger motifs. J Virol 2004, 78:12781–12787.

    Article  PubMed  CAS  Google Scholar 

  11. Varthakavi V, Smith RM, Bour SP, et al.: viral protein U counteracts a human host cell restriction that inhibits HIV-1 particle production. Proc Natl Acad Sci U S A 2003, 100:15154–15159.

    Article  PubMed  CAS  Google Scholar 

  12. Neil SJ, Eastman SW, Jouvenet N, Bieniasz PD: HIV-1 Vpu promotes release and prevents endocytosis of nascent retrovirus particles from the plasma membrane. PLoS Pathog 2006, 2:e39.

    Article  PubMed  Google Scholar 

  13. Stremlau M, Owens CM, Perron MJ, et al.: The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys. Nature 2004, 427:848–853.

    Article  PubMed  CAS  Google Scholar 

  14. Sayah DM, Sokolskaja E, Berthoux L, Luban J: Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1. Nature 2004, 430:569–573.

    Article  PubMed  CAS  Google Scholar 

  15. Hatziioannou T, Perez-Caballero D, Yang A, et al.: Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5alpha. Proc Natl Acad Sci U S A 2004, 101:10774–10779.

    Article  PubMed  CAS  Google Scholar 

  16. Keckesova Z, Ylinen LM, Towers GJ: The human and African green monkey TRIM5alpha genes encode Ref1 and Lv1 retroviral restriction factor activities. Proc Natl Acad Sci U S A 2004, 101:10780–10785.

    Article  PubMed  CAS  Google Scholar 

  17. Yap MW, Nisole S, Lynch C, Stoye JP: Trim5alpha protein restricts both HIV-1 and murine leukemia virus. Proc Natl Acad Sci U S A 2004, 101:10786–10791.

    Article  PubMed  CAS  Google Scholar 

  18. Perron MJ, Stremlau M, Song B, et al.: TRIM5alpha mediates the postentry block to N-tropic murine leukemia viruses in human cells. Proc Natl Acad Sci U S A 2004, 101:11827–11832.

    Article  PubMed  CAS  Google Scholar 

  19. Sokolskaja E, Berthoux L, Luban J: Cyclophilin A and TRIM5alpha independently regulate human immunodeficiency virus type 1 infectivity in human cells. J Virol 2006, 80:2855–2862.

    Article  PubMed  CAS  Google Scholar 

  20. Reymond A, Meroni G, Fantozzi A, et al.: The tripartite motif family identifies cell compartments. EMBO J 2001, 20:2140–2151.

    Article  PubMed  CAS  Google Scholar 

  21. Song B, Gold B, O’Huigin C, et al.: The B30.2(SPRY) domain of the retroviral restriction factor TRIM5alpha exhibits lineage-specific length and sequence variation in primates. J Virol 2005, 79:6111–6121.

    Article  PubMed  CAS  Google Scholar 

  22. Song B, Javanbakht H, Perron M, et al.: Retrovirus restriction by TRIM5alpha variants from Old World and New World primates. J Virol 2005, 79:3930–3937.

    Article  PubMed  CAS  Google Scholar 

  23. Ohkura S, Yap MW, Sheldon T, Stoye JP: All three variable regions of the TRIM5z{alpha}; B30.2 domain can contribute to the specificity of retrovirus restriction. J Virol 2006, 80:8554–8565.

    Article  PubMed  CAS  Google Scholar 

  24. Ylinen LM, Keckesova Z, Webb BL, et al.: Isolation of an active Lv1 gene from cattle indicates that tripartite motif protein-mediated innate immunity to retroviral infection is widespread among mammals. J Virol 2006, 80:7332–7338.

    Article  PubMed  CAS  Google Scholar 

  25. Si Z, Vandegraaff N, O’Huigin C, et al.: Evolution of a cytoplasmic tripartite motif (TRIM) protein in cows that restricts retroviral infection. Proc Natl Acad Sci U S A 2006, 103:7454–7459.

    Article  PubMed  CAS  Google Scholar 

  26. Nisole S, Lynch C, Stoye JP, Yap MW: A Trim5-cyclophilin A fusion protein found in owl monkey kidney cells can restrict HIV-1. Proc Natl Acad Sci U S A 2004, 101:13324–13328.

    Article  PubMed  CAS  Google Scholar 

  27. Franke EK, Yuan HE, Luban J: Specific incorporation of cyclophilin A into HIV-1 virions. Nature 1994, 372:359–362.

    Article  PubMed  CAS  Google Scholar 

  28. Perez-Caballero D, Hatziioannou T, Yang A, et al.: Human tripartite motif 5alpha domains responsible for retrovirus restriction activity and specificity. J Virol 2005, 79:8969–8978.

    Article  PubMed  CAS  Google Scholar 

  29. Javanbakht H, Diaz-Griffero F, Stremlau M, et al.: The contribution of RING and B-box 2 domains to retroviral restriction mediated by monkey TRIM5alpha. J Biol Chem 2005, 280:26933–26940.

    Article  PubMed  CAS  Google Scholar 

  30. Javanbakht H, Yuan W, Yeung DF, et al.: Characterization of TRIM5alpha trimerization and its contribution to human immunodeficiency virus capsid binding. Virology 2006, 353:234–246.

    Article  PubMed  CAS  Google Scholar 

  31. Vernet C, Boretto J, Mattei MG, et al.: Evolutionary study of multigenic families mapping close to the human MHC class I region. J Mol Evol 1993, 37:600–612.

    Article  PubMed  CAS  Google Scholar 

  32. Ponting C, Schultz J, Bork P: SPRY domains in ryanodine receptors (Ca(2+)-release channels). Trends Biochem Sci 1997, 22:193–194.

    Article  PubMed  CAS  Google Scholar 

  33. Grutter C, Briand C, Capitani G, et al.: Structure of the PRYSPRY-domain: implications for autoinflammatory diseases. FEBS Lett 2006, 580:99–106.

    Article  PubMed  Google Scholar 

  34. Woo JS, Imm JH, Min CK, et al.: Structural and functional insights into the B30.2/SPRY domain. EMBO J 2006, 25:1353–1363.

    Article  PubMed  CAS  Google Scholar 

  35. Masters SL, Yao S, Willson TA, et al.: The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par-4-binding residues. Nat Struct Mol Biol 2006, 13:77–84.

    Article  PubMed  CAS  Google Scholar 

  36. Nakayama EE, Miyoshi H, Nagai Y, Shioda T: A specific region of 37 amino acid residues in the SPRY (B30.2) domain of African green monkey TRIM5alpha determines species-specific restriction of simian immunodeficiency virus SIVmac infection. J Virol 2005, 79:8870–8877.

    Article  PubMed  CAS  Google Scholar 

  37. Sawyer SL, Wu LI, Emerman M, Malik HS: Positive selection of primate TRIM5alpha identifies a critical species-specific retroviral restriction domain. Proc Natl Acad Sci U S A 2005, 102:2832–2837.

    Article  PubMed  CAS  Google Scholar 

  38. 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, 79:3139–3145.

    Article  PubMed  CAS  Google Scholar 

  39. Yap MW, Nisole S, Stoye JP: A single amino acid change in the SPRY domain of human Trim5alpha leads to HIV-1 restriction. Curr Biol 2005, 15:73–78.

    Article  PubMed  CAS  Google Scholar 

  40. Li Y, Li X, Stremlau M, et al.: Removal of arginine 332 allows human TRIM5alpha to bind human immunodeficiency virus capsids and to restrict infection. J Virol 2006, 80:6738–6744.

    Article  PubMed  CAS  Google Scholar 

  41. Perron MJ, Stremlau M, Sodroski J: Two surface-exposed elements of the B30.2/SPRY domain as potency determinants of N-tropic murine leukemia virus restriction by human TRIM5alpha. J Virol 2006, 80:5631–5636.

    Article  PubMed  CAS  Google Scholar 

  42. Owens CM, Yang PC, Gottlinger H, Sodroski J: Human and simian immunodeficiency virus capsid proteins are major viral determinants of early, postentry replication blocks in simian cells. J Virol 2003, 77:726–731.

    Article  PubMed  CAS  Google Scholar 

  43. Dodding MP, Bock M, Yap MW, Stoye JP: Capsid processing requirements for abrogation of Fv1 and Ref1 restriction. J Virol 2005, 79:10571–10577.

    Article  PubMed  CAS  Google Scholar 

  44. Mortuza GB, Haire LF, Stevens A, et al.: High-resolution structure of a retroviral capsid hexameric amino-terminal domain. Nature 2004, 431:481–485.

    Article  PubMed  CAS  Google Scholar 

  45. Sebastian S, Luban J: TRIM5alpha selectively binds a restriction-sensitive retroviral capsid. Retrovirology 2005, 2:40.

    Article  PubMed  Google Scholar 

  46. Stremlau M, Perron M, Lee M, et al.: Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5alpha restriction factor. Proc Natl Acad Sci U S A 2006, 103:5514–5519.

    Article  PubMed  CAS  Google Scholar 

  47. Xu L, Yang L, Moitra PK, et al.: BTBD1 and BTBD2 colocalize to cytoplasmic bodies with the RBCC/tripartite motif protein, TRIM5delta. Exp Cell Res 2003, 288:84–93.

    Article  PubMed  CAS  Google Scholar 

  48. Diaz-Griffero F, Li X, Javanbakht H, et al.: Rapid turnover and polyubiquitylation of the retroviral restriction factor TRIM5. Virology 2006, 349:300–315.

    Article  PubMed  CAS  Google Scholar 

  49. Perez-Caballero D, Hatziioannou T, Zhang F, et al.: Restriction of human immunodeficiency virus type 1 by TRIM-CypA occurs with rapid kinetics and independently of cytoplasmic bodies, ubiquitin, and proteasome activity. J Virol 2005, 79:15567–15572.

    Article  PubMed  CAS  Google Scholar 

  50. Wu X, Anderson JL, Campbell EM, et al.: Proteasome inhibitors uncouple rhesus TRIM5alpha restriction of HIV-1 reverse transcription and infection. Proc Natl Acad Sci U S A 2006, 103:7465–7470.

    Article  PubMed  CAS  Google Scholar 

  51. Anderson JL, Campbell EM, Wu X, et al.: Proteasome Inhibition Reveals that a Functional Preintegration Complex Intermediate Can Be Generated during Restriction by Diverse TRIM5 Proteins. J Virol 2006, 80:9754–9760.

    Article  PubMed  CAS  Google Scholar 

  52. Berthoux L, Sebastian S, Sayah DM, Luban J: Disruption of human TRIM5alpha antiviral activity by nonhuman primate orthologues. J Virol 2005, 79:7883–7888.

    Article  PubMed  CAS  Google Scholar 

  53. Mische CC, Javanbakht H, Song B, et al.: Retroviral restriction factor TRIM5alpha is a trimer. J Virol 2005, 79:1446–14450.

    Article  Google Scholar 

  54. Song B, Diaz-Griffero F, Park DH, et al.: TRIM5alpha association with cytoplasmic bodies is not required for antiretroviral activity. Virology 2005, 343:201–211.

    Article  PubMed  CAS  Google Scholar 

  55. Yap MW, Dodding MP, Stoye JP: Trim-cyclophilin A fusion proteins can restrict human immunodeficiency virus type 1 infection at two distinct phases in the viral life cycle. J Virol 2006, 80:4061–4067.

    Article  PubMed  CAS  Google Scholar 

  56. Berthoux L, Sebastian S, Sokolskaja E, Luban J: Lv1 inhibition of human immunodeficiency virus type 1 is counteracted by factors that stimulate synthesis or nuclear translocation of viral cDNA. J Virol 2004, 78:11739–11750.

    Article  PubMed  CAS  Google Scholar 

  57. Speelmon EC, Livingston-Rosanoff D, Li SS, et al.: Genetic association of the antiviral restriction factor TRIM5alpha with human immunodeficiency virus type 1 infection. J Virol 2006, 80:2463–2471.

    Article  PubMed  CAS  Google Scholar 

  58. Sawyer SL, Wu LI, Akey JM, et al.: High-frequency persistence of an impaired allele of the retroviral defense gene TRIM5alpha in humans. Curr Biol 2006, 16:95–100.

    Article  PubMed  CAS  Google Scholar 

  59. Goldschmidt V, Bleiber G, May MT, et al.: Role of common human TRIM5alpha variants in HIV-1 disease progression. Retrovirology 2006, 3:54.

    Article  PubMed  Google Scholar 

  60. Javanbakht H, An P, Gold B, et al.: Effects of human TRIM5alpha polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection. Virology 2006, 354:15–27.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Research in Biomedicine, Via Vincenzo Vela 6, CH-6500, Bellinzona, Switzerland

    Jeremy Luban MD

Authors
  1. Sarah Sebastian PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeremy Luban MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeremy Luban MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sebastian, S., Luban, J. The retroviral restriction factor TRIM5α. Curr Infect Dis Rep 9, 167–173 (2007). https://doi.org/10.1007/s11908-007-0013-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11908-007-0013-4

Keywords

Search

Navigation