Medical Microbiology and Immunology

, Volume 204, Issue 5, pp 557–565 | Cite as

The innate immune roles of host factors TRIM5α and Cyclophilin A on HIV-1 replication

  • Yi-Qun Kuang
  • Hong-Liang Liu
  • Yong-Tang Zheng


During the long-term evolutionary history, the interaction between virus and host has driven the first-line barrier, innate immunity, to invading pathogens. Innate immune factor TRIM5α and host peptidyl-prolyl cistrans isomerase Cyclophilin A are two key players in the interaction between HIV-1 and host. Interestingly, Cyclophilin A is retrotransposed into the critical host gene, TRIM5, locus via LINE-1 element in some primate species including New World monkeys and Old World monkeys. This review aims to comprehensively discuss the sensing and immune activation procedures of TRIM5α innate signaling pathway through Cyclophilin A. It will then present the production of TRIMCyp chimeric gene and the different fusion patterns in primates. Finally, it will summarize the distinct restriction activity of TRIMCyp from different primates and explain the current understanding on the innate immune mechanisms involved in the early phase of the viral life cycle during HIV-1 replication.


TRIM5α Cyclophilin A HIV-1 Innate immune 



This work was supported in part by Grants from the Science and Technology Planning Project of Guangdong Province, China (2012B031800267), the Natural Science Foundation of Guangdong Province, China (S2013010011860), the National Natural Science Foundation of China (31200130 and 81371812) to Dr. Kuang, and Grants from the National Basic Research Program of China (2012CBA01305), the National Natural Science Foundation of China (81172876, 30671960 and U0832601) and the Knowledge Innovation Program of Chinese Academy of Sciences (KJZD-EW-L10-02) to Dr. Zheng.

Conflict of interest

All contributing authors declare no conflict of interest.


  1. 1.
    Sheehy AM, Gaddis NC, Choi JD, Malim MH (2002) Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418(6898):646–650. doi: 10.1038/nature00939 CrossRefPubMedGoogle Scholar
  2. 2.
    Heger E, Thielen A, Gilles R, Obermeier M, Lengauer T, Kaiser R, Trapp S (2012) APOBEC3G/F as one possible driving force for co-receptor switch of the human immunodeficiency virus-1. Med Microbiol Immunol 201(1):7–16. doi: 10.1007/s00430-011-0199-9 CrossRefPubMedGoogle Scholar
  3. 3.
    Stremlau M, Owens CM, Perron MJ, Kiessling M, Autissier P, Sodroski J (2004) The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in old World monkeys. Nature 427(6977):848–853. doi: 10.1038/nature02343 CrossRefPubMedGoogle Scholar
  4. 4.
    Neil SJ, Zang T, Bieniasz PD (2008) Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451(7177):425–430. doi: 10.1038/nature06553 CrossRefPubMedGoogle Scholar
  5. 5.
    Van Damme N, Goff D, Katsura C, Jorgenson RL, Mitchell R, Johnson MC, Stephens EB, Guatelli J (2008) The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe 3(4):245–252. doi: 10.1016/j.chom.2008.03.001 PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Segeral E, Yatim A, Emiliani S, Schwartz O, Benkirane M (2011) SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 474(7353):654–657. doi: 10.1038/nature10117 PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Hrecka K, Hao C, Gierszewska M, Swanson SK, Kesik-Brodacka M, Srivastava S, Florens L, Washburn MP, Skowronski J (2011) Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. Nature 474(7353):658–661. doi: 10.1038/nature10195 PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Goujon C, Moncorge O, Bauby H, Doyle T, Ward CC, Schaller T, Hue S, Barclay WS, Schulz R, Malim MH (2013) Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection. Nature 502(7472):559–562. doi: 10.1038/nature12542 CrossRefPubMedGoogle Scholar
  9. 9.
    Kane M, Yadav SS, Bitzegeio J, Kutluay SB, Zang T, Wilson SJ, Schoggins JW, Rice CM, Yamashita M, Hatziioannou T, Bieniasz PD (2013) MX2 is an interferon-induced inhibitor of HIV-1 infection. Nature 502(7472):563–566. doi: 10.1038/nature12653 PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Monteleone K, Di Maio P, Cacciotti G, Falasca F, Fraulo M, Falciano M, Mezzaroma I, D’Ettorre G, Turriziani O, Scagnolari C (2014) Interleukin-32 isoforms: expression, interaction with interferon-regulated genes and clinical significance in chronically HIV-1-infected patients. Med Microbiol Immunol 203(3):207–216. doi: 10.1007/s00430-014-0329-2 PubMedGoogle Scholar
  11. 11.
    Luban J, Bossolt KL, Franke EK, Kalpana GV, Goff SP (1993) Human immunodeficiency virus type 1 Gag protein binds to cyclophilins A and B. Cell 73(6):1067–1078. doi: 10.1016/0092-8674(93)90637-6 CrossRefPubMedGoogle Scholar
  12. 12.
    Berthoux L, Sebastian S, Sokolskaja E, Luban J (2005) Cyclophilin A is required for TRIM5α-mediated resistance to HIV-1 in old World monkey cells. Proc Natl Acad Sci USA 102(41):14849–14853. doi: 10.1073/pnas.0505659102 PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Stremlau M, Song B, Javanbakht H, Perron M, Sodroski J (2006) Cyclophilin A: an auxiliary but not necessary cofactor for TRIM5alpha restriction of HIV-1. Virology 351(1):112–120. doi: 10.1016/j.virol.2006.03.015 CrossRefPubMedGoogle Scholar
  14. 14.
    Sayah DM, Sokolskaja E, Berthoux L, Luban J (2004) Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1. Nature 430(6999):569–573. doi: 10.1038/nature02777 CrossRefPubMedGoogle Scholar
  15. 15.
    Nisole S, Lynch C, Stoye JP, Yap MW (2004) A Trim5-cyclophilin A fusion protein found in owl monkey kidney cells can restrict HIV-1. Proc Natl Acad Sci USA 101(36):13324–13328. doi: 10.1073/pnas.04046401010404640101 PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Liao CH, Kuang YQ, Liu HL, Zheng YT, Su B (2007) A novel fusion gene, TRIM5-Cyclophilin A in the pig-tailed macaque determines its susceptibility to HIV-1 infection. AIDS 21(Suppl 8):S19–S26. doi: 10.1097/01.aids.0000304692.09143.1 CrossRefPubMedGoogle Scholar
  17. 17.
    Virgen CA, Kratovac Z, Bieniasz PD, Hatziioannou T (2008) Independent genesis of chimeric TRIM5-cyclophilin proteins in two primate species. Proc Natl Acad Sci USA 105(9):3563–3568. doi: 10.1073/pnas.07092581050709258105 PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Brennan G, Kozyrev Y, Hu SL (2008) TRIMCyp expression in old World primates Macaca nemestrina and Macaca fascicularis. Proc Natl Acad Sci USA 105(9):3569–3574. doi: 10.1073/pnas.07095111050709511105 PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Kuang YQ, Tang X, Liu FL, Jiang XL, Zhang YP, Gao G, Zheng YT (2009) Genotyping of TRIM5 locus in northern pig-tailed macaques (Macaca leonina), a primate species susceptible to human immunodeficiency virus type 1 infection. Retrovirology 6:58. doi: 10.1186/1742-4690-6-581742-4690-6-58 PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Cao G, Nie WH, Liu FL, Kuang YQ, Wang JH, Su WT, Zheng YT (2011) Identification of the TRIM5/TRIMCyp heterozygous genotype in Macaca assamensis. Dongwuxue Yanjiu 32(1):40–49. doi: 10.3724/SP.J.1141.2011.01040 PubMedGoogle Scholar
  21. 21.
    Manel N, Hogstad B, Wang Y, Levy DE, Unutmaz D, Littman DR (2010) A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells. Nature 467(7312):214–217. doi: 10.1038/nature09337 PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Sun S, Guo M, Zhang JB, Ha A, Yokoyama KK, Chiu RH (2014) Cyclophilin A (CypA) interacts with NF-kappaB subunit, p65/RelA, and contributes to NF-kappaB activation signaling. PLoS One 9(8):e96211. doi: 10.1371/journal.pone.0096211 PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Pertel T, Hausmann S, Morger D, Zuger S, Guerra J, Lascano J, Reinhard C, Santoni FA, Uchil PD, Chatel L, Bisiaux A, Albert ML, Strambio-De-Castillia C, Mothes W, Pizzato M, Grutter MG, Luban J (2011) TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature 472(7343):361–365. doi: 10.1038/nature09976 PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    van der Vlist M, van der Aar AM, Gringhuis SI, Geijtenbeek TB (2011) Innate signaling in HIV-1 infection of dendritic cells. Curr Opin HIV AIDS 6(5):348–352. doi: 10.1097/COH.0b013e328349a2d1 CrossRefPubMedGoogle Scholar
  25. 25.
    Gao D, Wu J, Wu YT, Du F, Aroh C, Yan N, Sun L, Chen ZJ (2013) Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science 341(6148):903–906. doi: 10.1126/science.1240933 CrossRefPubMedGoogle Scholar
  26. 26.
    Franke EK, Yuan HE, Luban J (1994) Specific incorporation of cyclophilin A into HIV-1 virions. Nature 372(6504):359–362. doi: 10.1038/372359a0 CrossRefPubMedGoogle Scholar
  27. 27.
    Thali M, Bukovsky A, Kondo E, Rosenwirth B, Walsh CT, Sodroski J, Gottlinger HG (1994) Functional association of cyclophilin A with HIV-1 virions. Nature 372(6504):363–365. doi: 10.1038/372363a0 CrossRefPubMedGoogle Scholar
  28. 28.
    Ott DE, Coren LV, Johnson DG, Sowder RC 2nd, Arthur LO, Henderson LE (1995) Analysis and localization of cyclophilin A found in the virions of human immunodeficiency virus type 1 MN strain. AIDS Res Hum Retrovir 11(9):1003–1006CrossRefPubMedGoogle Scholar
  29. 29.
    Braaten D, Luban J (2001) Cyclophilin A regulates HIV-1 infectivity, as demonstrated by gene targeting in human T cells. EMBO J 20(6):1300–1309. doi: 10.1093/emboj/20.6.1300 PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Takeuchi H, Ishii H, Kuwano T, Inagaki N, Akari H, Matano T (2012) Host cell species-specific effect of cyclosporine A on simian immunodeficiency virus replication. Retrovirology 9:3. doi: 10.1186/1742-4690-9-31742-4690-9-3 PubMedCentralCrossRefPubMedGoogle Scholar
  31. 31.
    Ikeda Y, Ylinen LM, Kahar-Bador M, Towers GJ (2004) Influence of gag on human immunodeficiency virus type 1 species-specific tropism. J Virol 78(21):11816–11822. doi: 10.1128/JVI.78.21.11816-11822.2004 PubMedCentralCrossRefPubMedGoogle Scholar
  32. 32.
    Hatziioannou T, Perez-Caballero D, Yang A, Cowan S, Bieniasz PD (2004) Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5alpha. Proc Natl Acad Sci USA 101(29):10774–10779. doi: 10.1073/pnas.04023611010402361101 PubMedCentralCrossRefPubMedGoogle Scholar
  33. 33.
    Keckesova Z, Ylinen LM, Towers GJ (2004) The human and African green monkey TRIM5alpha genes encode Ref1 and Lv1 retroviral restriction factor activities. Proc Natl Acad Sci USA 101(29):10780–10785. doi: 10.1073/pnas.04024741010402474101 PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Perron MJ, Stremlau M, Song B, Ulm W, Mulligan RC, Sodroski J (2004) TRIM5alpha mediates the postentry block to N-tropic murine leukemia viruses in human cells. Proc Natl Acad Sci USA 101(32):11827–11832. doi: 10.1073/pnas.04033641010403364101 PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Yap MW, Nisole S, Lynch C, Stoye JP (2004) Trim5alpha protein restricts both HIV-1 and murine leukemia virus. Proc Natl Acad Sci USA 101(29):10786–10791. doi: 10.1073/pnas.04028761010402876101 PubMedCentralCrossRefPubMedGoogle Scholar
  36. 36.
    Hofmann W, Schubert D, LaBonte J, Munson L, Gibson S, Scammell J, Ferrigno P, Sodroski J (1999) Species-specific, postentry barriers to primate immunodeficiency virus infection. J Virol 73(12):10020–10028PubMedCentralPubMedGoogle Scholar
  37. 37.
    Nisole S, Stoye JP, Saib A (2005) TRIM family proteins: retroviral restriction and antiviral defence. Nat Rev Microbiol 3(10):799–808. doi: 10.1038/nrmicro1248 CrossRefPubMedGoogle Scholar
  38. 38.
    Song B, Javanbakht H, Perron M, Park DH, Stremlau M, Sodroski J (2005) Retrovirus restriction by TRIM5alpha variants from Old World and New World primates. J Virol 79(7):3930–3937. doi: 10.1128/JVI.79.7.3930-3937.2005 PubMedCentralCrossRefPubMedGoogle Scholar
  39. 39.
    Si Z, Vandegraaff N, O’Huigin C, Song B, Yuan W, Xu C, Perron M, Li X, Marasco WA, Engelman A, Dean M, Sodroski J (2006) Evolution of a cytoplasmic tripartite motif (TRIM) protein in cows that restricts retroviral infection. Proc Natl Acad Sci USA 103(19):7454–7459. doi: 10.1073/pnas.0600771103 PubMedCentralCrossRefPubMedGoogle Scholar
  40. 40.
    Stremlau M, Perron M, Lee M, Li Y, Song B, Javanbakht H, Diaz-Griffero F, Anderson DJ, Sundquist WI, Sodroski J (2006) Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5alpha restriction factor. Proc Natl Acad Sci USA 103(14):5514–5519. doi: 10.1073/pnas.0509996103 PubMedCentralCrossRefPubMedGoogle Scholar
  41. 41.
    Sokolskaja E, Berthoux L, Luban J (2006) Cyclophilin A and TRIM5alpha independently regulate human immunodeficiency virus type 1 infectivity in human cells. J Virol 80(6):2855–2862. doi: 10.1128/JVI.80.6.2855-2862.2006 PubMedCentralCrossRefPubMedGoogle Scholar
  42. 42.
    Lin TY, Emerman M (2008) Determinants of cyclophilin A-dependent TRIM5 alpha restriction against HIV-1. Virology 379(2):335–341. doi: 10.1016/j.virol.2008.06.037 PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    Keckesova Z, Ylinen LM, Towers GJ (2006) Cyclophilin A renders human immunodeficiency virus type 1 sensitive to old World monkey but not human TRIM5 alpha antiviral activity. J Virol 80(10):4683–4690. doi: 10.1128/JVI.80.10.4683-4690.2006 PubMedCentralCrossRefPubMedGoogle Scholar
  44. 44.
    Wu X, Anderson JL, Campbell EM, Joseph AM, Hope TJ (2006) Proteasome inhibitors uncouple rhesus TRIM5alpha restriction of HIV-1 reverse transcription and infection. Proc Natl Acad Sci USA 103(19):7465–7470. doi: 10.1073/pnas.0510483103 PubMedCentralCrossRefPubMedGoogle Scholar
  45. 45.
    Diaz-Griffero F, Gallo DE, Hope TJ, Sodroski J (2011) Trafficking of some old world primate TRIM5alpha proteins through the nucleus. Retrovirology 8:38. doi: 10.1186/1742-4690-8-381742-4690-8-38 PubMedCentralCrossRefPubMedGoogle Scholar
  46. 46.
    Kutluay SB, Perez-Caballero D, Bieniasz PD (2013) Fates of retroviral core components during unrestricted and TRIM5-restricted infection. PLoS Pathog 9(3):e1003214. doi: 10.1371/journal.ppat.1003214 PubMedCentralCrossRefPubMedGoogle Scholar
  47. 47.
    Johnson WE, Sawyer SL (2009) Molecular evolution of the antiretroviral TRIM5 gene. Immunogenetics 61(3):163–176. doi: 10.1007/s00251-009-0358-y CrossRefPubMedGoogle Scholar
  48. 48.
    Zhang F, Hatziioannou T, Perez-Caballero D, Derse D, Bieniasz PD (2006) Antiretroviral potential of human tripartite motif-5 and related proteins. Virology 353(2):396–409. doi: 10.1016/j.virol.2006.05.035 CrossRefPubMedGoogle Scholar
  49. 49.
    Sawyer SL, Emerman M, Malik HS (2007) Discordant evolution of the adjacent antiretroviral genes TRIM22 and TRIM5 in mammals. PLoS Pathog 3(12):e197. doi: 10.1371/journal.ppat.0030197 PubMedCentralCrossRefPubMedGoogle Scholar
  50. 50.
    Tareen SU, Sawyer SL, Malik HS, Emerman M (2009) An expanded clade of rodent Trim5 genes. Virology 385(2):473–483. doi: 10.1016/j.virol.2008.12.01851 PubMedCentralCrossRefPubMedGoogle Scholar
  51. 51.
    Shi M, Deng W, Bi E, Mao K, Ji Y, Lin G, Wu X, Tao Z, Li Z, Cai X, Sun S, Xiang C, Sun B (2008) TRIM30 alpha negatively regulates TLR-mediated NF-kappa B activation by targeting TAB 2 and TAB 3 for degradation. Nat Immunol 9(4):369–377. doi: 10.1038/ni1577
  52. 52.
    Bowie AG (2008) TRIM-ing down Tolls. Nat Immunol 9(4):348–350. doi: 10.1038/ni0408-348 CrossRefPubMedGoogle Scholar
  53. 53.
    Tareen SU, Emerman M (2011) Human Trim5alpha has additional activities that are uncoupled from retroviral capsid recognition. Virology 409(1):113–120. doi: 10.1016/j.virol.2010.09.018 PubMedCentralCrossRefPubMedGoogle Scholar
  54. 54.
    Luban J (2012) Innate immune sensing of HIV-1 by dendritic cells. Cell Host Microbe 12(4):408–418. doi: 10.1016/j.chom.2012.10.002 PubMedCentralCrossRefPubMedGoogle Scholar
  55. 55.
    Aiken C, Joyce S (2011) Immunology: TRIM5 does double duty. Nature 472(7343):305–306. doi: 10.1038/472305a CrossRefPubMedGoogle Scholar
  56. 56.
    Tareen SU, Emerman M (2011) Trim5 TAKes on pattern recognition. Cell Host Microbe 9(5):349–350. doi: 10.1016/j.chom.2011.05.003 PubMedCentralCrossRefPubMedGoogle Scholar
  57. 57.
    Uchil PD, Hinz A, Siegel S, Coenen-Stass A, Pertel T, Luban J, Mothes W (2013) TRIM protein-mediated regulation of inflammatory and innate immune signaling and its association with antiretroviral activity. J Virol 87(1):257–272. doi: 10.1128/JVI.01804-12 PubMedCentralCrossRefPubMedGoogle Scholar
  58. 58.
    Versteeg GA, Rajsbaum R, Sanchez-Aparicio MT, Maestre AM, Valdiviezo J, Shi M, Inn KS, Fernandez-Sesma A, Jung J, Garcia-Sastre A (2013) The E3-ligase TRIM family of proteins regulates signaling pathways triggered by innate immune pattern-recognition receptors. Immunity 38(2):384–398. doi: 10.1016/j.immuni.2012.11.013 PubMedCentralCrossRefPubMedGoogle Scholar
  59. 59.
    Grutter MG, Luban J (2012) TRIM5 structure, HIV-1 capsid recognition, and innate immune signaling. Curr Opin Virol 2(2):142–150. doi: 10.1016/j.coviro.2012.02.003 PubMedCentralCrossRefPubMedGoogle Scholar
  60. 60.
    Arriagada G, Muntean LN, Goff SP (2011) SUMO-interacting motifs of human TRIM5alpha are important for antiviral activity. PLoS Pathog 7(4):e1002019. doi: 10.1371/journal.ppat.1002019 PubMedCentralCrossRefPubMedGoogle Scholar
  61. 61.
    Brandariz-Nunez A, Roa A, Valle-Casuso JC, Biris N, Ivanov D, Diaz-Griffero F (2013) Contribution of SUMO-interacting motifs and SUMOylation to the antiretroviral properties of TRIM5alpha. Virology 435(2):463–471. doi: 10.1016/j.virol.2012.09.042 PubMedCentralCrossRefPubMedGoogle Scholar
  62. 62.
    Lukic Z, Goff SP, Campbell EM, Arriagada G (2013) Role of SUMO-1 and SUMO interacting motifs in rhesus TRIM5alpha-mediated restriction. Retrovirology 10:10. doi: 10.1186/1742-4690-10-10 PubMedCentralCrossRefPubMedGoogle Scholar
  63. 63.
    Nepveu-Traversy ME, Berthoux L (2014) The conserved sumoylation consensus site in TRIM5alpha modulates its immune activation functions. Virus Res 184:30–38. doi: 10.1016/j.virusres.2014.02.013 CrossRefPubMedGoogle Scholar
  64. 64.
    Ribeiro IP, Menezes AN, Moreira MA, Bonvicino CR, Seuanez HN, Soares MA (2005) Evolution of cyclophilin A and TRIMCyp retrotransposition in New World primates. J Virol 79(23):14998–15003. doi: 10.1128/JVI.79.23.14998-15003.2005 PubMedCentralCrossRefPubMedGoogle Scholar
  65. 65.
    Yu CQ, Na L, Lv XL, Liu JD, Liu XM, Ji F, Zheng YH, Du HL, Kong XG, Zhou JH (2013) The TRIMCyp genotype in four species of macaques in China. Immunogenetics 65(3):185–193. doi: 10.1007/s00251-012-0670-9 CrossRefPubMedGoogle Scholar
  66. 66.
    Wilson SJ, Webb BL, Ylinen LM, Verschoor E, Heeney JL, Towers GJ (2008) Independent evolution of an antiviral TRIMCyp in rhesus macaques. Proc Natl Acad Sci USA 105(9):3557–3562. doi: 10.1073/pnas.0709003105 PubMedCentralCrossRefPubMedGoogle Scholar
  67. 67.
    Newman RM, Hall L, Kirmaier A, Pozzi LA, Pery E, Farzan M, O’Neil SP, Johnson W (2008) Evolution of a TRIM5–CypA splice isoform in old world monkeys. PLoS Pathog 4(2):e1000003. doi: 10.1371/journal.ppat.1000003 PubMedCentralCrossRefPubMedGoogle Scholar
  68. 68.
    Brennan G, Kozyrev Y, Kodama T, Hu SL (2007) Novel TRIM5 isoforms expressed by Macaca nemestrina. J Virol 81(22):12210–12217. doi: 10.1128/JVI.02499-06 PubMedCentralCrossRefPubMedGoogle Scholar
  69. 69.
    Ylinen LM, Price AJ, Rasaiyaah J, Hue S, Rose NJ, Marzetta F, James LC, Towers GJ (2010) Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity. PLoS Pathog 6(8):e1001062. doi: 10.1371/journal.ppat.1001062 PubMedCentralCrossRefPubMedGoogle Scholar
  70. 70.
    Price AJ, Marzetta F, Lammers M, Ylinen LM, Schaller T, Wilson SJ, Towers GJ, James LC (2009) Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. Nat Struct Mol Biol 16(10):1036–1042. doi: 10.1038/nsmb.1667 PubMedCentralCrossRefPubMedGoogle Scholar
  71. 71.
    Dietrich EA, Brennan G, Ferguson B, Wiseman RW, O’Connor D, Hu SL (2011) Variable prevalence and functional diversity of the antiretroviral restriction factor TRIMCyp in Macaca fascicularis. J Virol 85(19):9956–9963. doi: 10.1128/JVI.00097-11 PubMedCentralCrossRefPubMedGoogle Scholar
  72. 72.
    Diaz-Griffero F, Kar A, Perron M, Xiang SH, Javanbakht H, Li X, Sodroski J (2007) Modulation of retroviral restriction and proteasome inhibitor-resistant turnover by changes in the TRIM5alpha B-box 2 domain. J Virol 81(19):10362–10378. doi: 10.1128/JVI.00703-07 PubMedCentralCrossRefPubMedGoogle Scholar
  73. 73.
    Caines ME, Bichel K, Price AJ, McEwan WA, Towers GJ, Willett BJ, Freund SM, James LC (2012) Diverse HIV viruses are targeted by a conformationally dynamic antiviral. Nat Struct Mol Biol 19(4):411–416. doi: 10.1038/nsmb.2253 PubMedCentralCrossRefPubMedGoogle Scholar
  74. 74.
    Luban J (2007) Cyclophilin A, TRIM5, and resistance to human immunodeficiency virus type 1 infection. J Virol 81(3):1054–1061. doi: 10.1128/JVI.01519-06 PubMedCentralCrossRefPubMedGoogle Scholar
  75. 75.
    Javanbakht H, Diaz-Griffero F, Yuan W, Yeung DF, Li X, Song B, Sodroski J (2007) The ability of multimerized cyclophilin A to restrict retrovirus infection. Virology 367(1):19–29. doi: 10.1016/j.virol.2007.04.034 PubMedCentralCrossRefPubMedGoogle Scholar
  76. 76.
    Nepveu-Traversy ME, Berube J, Berthoux L (2009) TRIM5alpha and TRIMCyp form apparent hexamers and their multimeric state is not affected by exposure to restriction-sensitive viruses or by treatment with pharmacological inhibitors. Retrovirology 6:100. doi: 10.1186/1742-4690-6-100 PubMedCentralCrossRefPubMedGoogle Scholar
  77. 77.
    Perez-Caballero D, Hatziioannou T, Zhang F, Cowan S, Bieniasz PD (2005) 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 79(24):15567–15572. doi: 10.1128/JVI.79.24.15567-15572.2005 PubMedCentralCrossRefPubMedGoogle Scholar
  78. 78.
    Yap MW, Dodding MP, Stoye JP (2006) Trim-cyclophilin A fusion proteins can restrict human immunodeficiency virus type 1 infection at two distinct phases in the viral life cycle. J Virol 80(8):4061–4067. doi: 10.1128/JVI.80.8.4061-4067.2006 PubMedCentralCrossRefPubMedGoogle Scholar
  79. 79.
    Anderson JL, Campbell EM, Wu X, Vandegraaff N, Engelman A, Hope TJ (2006) Proteasome inhibition reveals that a functional preintegration complex intermediate can be generated during restriction by diverse TRIM5 proteins. J Virol 80(19):9754–9760. doi: 10.1128/JVI.01052-06 PubMedCentralCrossRefPubMedGoogle Scholar
  80. 80.
    de Silva S, Wu L (2011) TRIM5 acts as more than a retroviral restriction factor. Viruses 3(7):1204–1209. doi: 10.3390/v3071204 PubMedCentralCrossRefPubMedGoogle Scholar
  81. 81.
    Wongsrikeao P, Saenz D, Rinkoski T, Otoi T, Poeschla E (2011) Antiviral restriction factor transgenesis in the domestic cat. Nat Methods 8(10):853–859. doi: 10.1038/nmeth.1703 PubMedCentralCrossRefPubMedGoogle Scholar
  82. 82.
    Chan E, Towers GJ, Qasim W (2014) Gene therapy strategies to exploit TRIM derived restriction factors against HIV-1. Viruses 6(1):243–263. doi: 10.3390/v6010243 PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Yi-Qun Kuang
    • 1
    • 2
  • Hong-Liang Liu
    • 3
  • Yong-Tang Zheng
    • 4
  1. 1.Center for Translational Medicine, Huaihe Clinical InstituteHenan UniversityKaifengPeople’s Republic of China
  2. 2.Guangdong Institute of Public HealthGuangdong Center for Disease Control and PreventionGuangzhouPeople’s Republic of China
  3. 3.Pharmaceutical CollegeHenan UniversityKaifengPeople’s Republic of China
  4. 4.Key Laboratory of Animal Models and Human Diseases Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of ZoologyChinese Academy of SciencesKunmingPeople’s Republic of China

Personalised recommendations