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From Lentiviruses to Lentivirus Vectors

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Part of the Methods in Molecular Biology™ book series (MIMB,volume 229)

Abstract

Although a member of the lentivirus group, the equine infectious anemia virus (EIAV) was the first nonplant virus discovered in the first decade of the 20th century (1), lentiviruses were considered as rather mysterious viruses until the isolation of the human immunodeficiency virus type 1 (HIV-1) occurred at the beginning of 1980s. Lentiviruses are enveloped viruses carrying two copies of single-strand positive (i.e., codifying) RNA and are considered the ethiologic agents of acquired immunodeficiency syndromes for a broad range of animal species, such as humans, primates, cats, horses, sheep, and goats. Such syndromes develop in multiorgan diseases and share a long period of incubation (with viral persistence despite a potent immunological response) and a fatal outcome. The name lentiviruses (from Latin, lenti, slow) originated from the uniquely prolonged incubation period (i.e., from months to years) needed for the infecting virus to induce the disease, a feature joining the most popular lentivirus, HIV-1, with a large number of nonprimates lentiviruses. Lentiviruses belong to the Lentiviridae subfamily of the Retroviridae family, which also includes the Oncoviridae, for the most part viruses inducing cell transformation, and the Spumaviridae, viruses establishing persistent as well as nonpathogenic infections (a deeper treatment of this topic can be found in ref. 2).

Keywords

  • Simian Immunodeficiency Virus
  • Feline Immunodeficiency Virus
  • Bovine Leukemia Virus
  • Equine Infectious Anemia Virus
  • Packaging Construct

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Vallee, H. and Carré, H. (1904) Nature infectieuse de ľanemie de cheval. C. R. Acad. Sci. 139, 331–333.

    Google Scholar 

  2. Coffin, J. M., Huges, S. H., and Varmus, H. E. (1997) Retroviruses. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

    Google Scholar 

  3. Pereira, L. A., Bentley, K., Peeters, A., Churchill, M. J., and Deacon, N. J. (2000) A compilation of cellular transcription factor interactions with the HIV-1 LTR promoter. Nucleic Acids Res. 28, 663–668.

    PubMed  CrossRef  CAS  Google Scholar 

  4. Freed, E. O. (1998) HIV-1 gag proteins: diverse functions in the virus life cycle. Virology 251, 1–15.

    PubMed  CrossRef  CAS  Google Scholar 

  5. Li, X., Quan, Y., and Wainberg, M. A. (1997) Controlling elements in replication of the human immunodeficiency virus type 1. Cell Mol. Biol. (Noisy.-le-grand) 43, 443–454.

    CAS  Google Scholar 

  6. Wyatt, R. and Sodroski, J. (1998) The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280, 1884–1888.

    PubMed  CrossRef  CAS  Google Scholar 

  7. Kim, V. N., Mitrophanous, K., Kingsman, S. M., and Kingsman, A. J. (1998) Minimal requirement for a lentivirus vector based on human immunodeficiency virus type 1. J. Virol. 72, 811–816.

    PubMed  CAS  Google Scholar 

  8. Chinnasamy, D., Chinnasamy, N., Enriquez, M. J., Otsu, M., Morgan, R. A., and Candotti, F. (2000) Lentiviral-mediated gene transfer into human lymphocytes: role of HIV-1 accessory proteins. Blood 96, 1309–1316.

    PubMed  CAS  Google Scholar 

  9. Inubushi, R. and Adachi, A. (1999) Cell-dependent function of HIV-1 Vif for virus replication (Review). Int. J. Mol. Med. 3, 473–476.

    PubMed  CAS  Google Scholar 

  10. Sheehy, A. M., Gaddis, N. C., Choi, J. O., and Malim, M. H. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral VIF protein. Nature 418, 646–650.

    Google Scholar 

  11. Kafri, T., Blomer, U., Peterson, D. A., Gage, F. H., and Verma, I. M. (1997) Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors. Nat. Genet. 17, 314–317.

    PubMed  CrossRef  CAS  Google Scholar 

  12. Bukrinsky, M. and Adzhubei, A. (1999) Viral protein R of HIV-1. Rev. Med. Virol. 9, 39–49.

    PubMed  CrossRef  CAS  Google Scholar 

  13. Elder, R. T., Benko, Z., and Zhao, Y. (2002) HIV-1 VPR modulates cell cycle G2/M transition through an alternative cellular mechanism other than the classic mitotic checkpoints. Front. Biosci. 7, d349–d357.

    PubMed  CrossRef  CAS  Google Scholar 

  14. Kappes, J. C. (1995) Viral protein x. Curr. Top. Microbiol. Immunol. 193, 121–132.

    PubMed  CAS  Google Scholar 

  15. Connor, R. I., Chen, B. K., Choe, S., and Landau, N. R. (1995) Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes. Virology 206, 935–944.

    PubMed  CrossRef  CAS  Google Scholar 

  16. Mahalingam, S., Ayyavoo, V., Patel, M., Kieber-Emmons, T., and Weiner, D. B. (1997) Nuclear import, virion incorporation, and cell cycle arrest/differentiation are mediated by distinct functional domains of human immunodeficiency virus type 1 Vpr. J. Virol. 71, 6339–6347.

    PubMed  CAS  Google Scholar 

  17. Eckstein, D. A., Sherman, M. P., Penn, M. L., et al. (2001) HIV-1 Vpr enhances viral burden by facilitating infection of tissue macrophages but not nondividing CD4+ T cells. J. Exp. Med. 194, 1407–1419.

    PubMed  CrossRef  CAS  Google Scholar 

  18. De Noronha, C. M., Sherman, M. P., Lin, H. W., et al. (2001) Dynamic disruptions in nuclear envelope architecture and integrity induced by HIV-1 Vpr. Science 294, 1105–1108.

    PubMed  CrossRef  Google Scholar 

  19. Jowett, J. B., Xie, Y. M., and Chen, I. S. (1999) The presence of human immuno-deficiency virus type 1 Vpr correlates with a decrease in the frequency of mutations in a plasmid shuttle vector. J. Virol. 73, 7132–7137.

    PubMed  CAS  Google Scholar 

  20. Mansky, L. M. (1996) The mutation rate of human immunodeficiency virus type 1 is influenced by the vpr gene. Virology 222, 391–400.

    PubMed  CrossRef  CAS  Google Scholar 

  21. Marcello, A., Zoppe, M., and Giacca, M. (2001) Multiple modes of transcriptional regulation by the HIV-1 Tat transactivator. IUBMB Life 51, 175–181.

    PubMed  CrossRef  CAS  Google Scholar 

  22. Jones, K. A. (1997) Taking a new TAK on tat transactivation. Genes Dev. 11, 2593–2599.

    PubMed  CrossRef  CAS  Google Scholar 

  23. Cujec, T. P., Cho, H., Maldonado, E., Meyer, J., Reinberg, D., and Peterlin, B. M. (1997) The human immunodeficiency virus transactivator Tat interacts with the RNA polymerase II holoenzyme. Mol. Cell Biol. 17, 1817–1823.

    PubMed  CAS  Google Scholar 

  24. Benkirane, M., Chun, R. F., Xiao, H., et al. (1998) Activation of integrated provirus requires histone acetyltransferase. p300 and P/CAF are coactivators for HIV-1 Tat. J. Biol. Chem. 273, 24,898–24,905.

    PubMed  CrossRef  CAS  Google Scholar 

  25. Roebuck, K. A., Rabbi, M. F., and Kagnoff, M. F. (1997) HIV-1 Tat protein can transactivate a heterologous TATAA element independent of viral promoter sequences and the transactivation response element. AIDS 11, 139–146.

    PubMed  CrossRef  CAS  Google Scholar 

  26. de Parseval, A. and Elder, J. H. (1999) Demonstration that orf2 encodes the feline immunodeficiency virus transactivating (Tat) protein and characterization of a unique gene product with partial rev activity. J. Virol. 73, 608–617.

    PubMed  Google Scholar 

  27. Purcell, D. F. and Martin, M. A. (1993) Alternative splicing of human immuno-deficiency virus type 1 mRNA modulates viral protein expression, replication, and infectivity. J. Virol. 67, 6365–6378.

    PubMed  CAS  Google Scholar 

  28. Pollard, V. W. and Malim, M. H. (1998) The HIV-1 Rev protein. Annu. Rev. Microbiol. 52, 491–532.

    PubMed  CrossRef  CAS  Google Scholar 

  29. Fukumori, T., Kagawa, S., Iida, S., et al. (1999) Rev-dependent expression of three species of HIV-1 mRNAs (review). Int. J. Mol. Med. 3, 297–302.

    PubMed  CAS  Google Scholar 

  30. Yi, R., Bogerd, H. P., and Cullen, B. R. (2002) Recruitment of the Crm1 nuclear export factor is sufficient to induce cytoplasmic expression of incompletely spliced human immunodeficiency virus mRNAs. J. Virol. 76, 2036–2042.

    PubMed  CrossRef  CAS  Google Scholar 

  31. Ruhl, M., Himmelspach, M., Bahr, G. M., et al. (1993) Eukaryotic initiation factor 5A is a cellular target of the human immunodeficiency virus type 1 Rev activation domain mediating trans-activation. J. Cell Biol. 123, 1309–1320.

    PubMed  CrossRef  CAS  Google Scholar 

  32. Bogerd, H. P., Fridell, R. A., Madore, S., and Cullen, B. R. (1995) Identification of a novel cellular cofactor for the Rev/Rex class of retroviral regulatory proteins. Cell 82, 485–494.

    PubMed  CrossRef  CAS  Google Scholar 

  33. Fritz, C. C., Zapp, M. L., and Green, M. R. (1995) A human nucleoporin-like protein that specifically interacts with HIV Rev. Nature 376, 530–533.

    PubMed  CrossRef  CAS  Google Scholar 

  34. Reddy, T. R., Xu, W., Mau, J. K., et al. (1999) Inhibition of HIV replication by dominant negative mutants of Sam68, a functional homolog of HIV-1 Rev. Nat. Med. 5, 635–642.

    PubMed  CrossRef  CAS  Google Scholar 

  35. Boris-Lawrie, K., Roberts, T. M., and Hull, S. (2001) Retroviral RNA elements integrate components of post-transcriptional gene expression. Life Sci. 69, 2697–2709.

    PubMed  CrossRef  CAS  Google Scholar 

  36. Zolotukhin, A. S., Valentin, A., Pavlakis, G. N., and Felber, B. K. (1994) Continuous propagation of RRE(-) and Rev(-)RRE(-) human immunodeficiency virus type 1 molecular clones containing a cis-acting element of simian retrovirus type 1 in human peripheral blood lymphocytes. J. Virol. 68, 7944–7952.

    PubMed  CAS  Google Scholar 

  37. Gasmi, M., Glynn, J., Jin, M. J., Jolly, D. J., Yee, J. K., and Chen, S. T. (1999) Requirements for efficient production and transduction of human immunodeficiency virus type 1-based vectors. J. Virol. 73, 1828–1834.

    PubMed  CAS  Google Scholar 

  38. Bour, S. and Strebel, K. (2000) HIV accessory proteins: multifunctional components of a complex system. Adv. Pharmacol. 48, 75–120.

    PubMed  CrossRef  CAS  Google Scholar 

  39. Geyer, M., Fackler, O. T., and Peterlin, B. M. (2001) Structure—function relationships in HIV-1 Nef. EMBO Rep. 2, 580–585.

    PubMed  CrossRef  CAS  Google Scholar 

  40. Arold, S. T. and Baur, A. S. (2001) Dynamic Nef and Nef dynamics: how structure could explain the complex activities of this small HIV protein. Trends Biochem. Sci. 26, 356–363.

    PubMed  CrossRef  CAS  Google Scholar 

  41. Chazal, N., Singer, G., Aiken, C., Hammarskjold, M. L., and Rekosh, D. (2001) Human immunodeficiency virus type 1 particles pseudotyped with envelope proteins that fuse at low pH no longer require Nef for optimal infectivity. J. Virol. 75, 4014–4018.

    PubMed  CrossRef  CAS  Google Scholar 

  42. Clapham, P. R. and McKnight, A. (2001) HIV-1 receptors and cell tropism. Br. Med. Bull. 58, 43–59.

    PubMed  CrossRef  CAS  Google Scholar 

  43. Jonckheere, H., Anne, J., and De Clercq, E. (2000) The HIV-1 reverse transcription (RT) process as target for RT inhibitors. Med. Res. Rev. 20, 129–154.

    PubMed  CrossRef  CAS  Google Scholar 

  44. Gallay, P., Hope, T., Chin, D., and Trono, D. (1997) HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway. Proc. Natl. Acad. Sci. USA 94, 9825–9830.

    PubMed  CrossRef  CAS  Google Scholar 

  45. Popov, S., Rexach, M., Ratner, L., Blobel, G., and Bukrinsky, M. (1998) Viral protein R regulates docking of the HIV-1 preintegration complex to the nuclear pore complex. J. Biol. Chem. 273, 13,347–13,352.

    PubMed  CrossRef  CAS  Google Scholar 

  46. Jenkins, Y., McEntee, M., Weis, K., and Greene, W. C. (1998) Characterization of HIV-1 vpr nuclear import: analysis of signals and pathways. J. Cell Biol. 143, 875–885.

    PubMed  CrossRef  CAS  Google Scholar 

  47. Haffar, O. K., Popov, S., Dubrovsky, L., et al. (2000) Two nuclear localization signals in the HIV-1 matrix protein regulate nuclear import of the HIV-1 pre-integration complex. J. Mol. Biol. 299, 359–368.

    PubMed  CrossRef  CAS  Google Scholar 

  48. Zennou, V., Petit, C., Guetard, D., Nerhbass, U., Montagnier, L., and Charneau, P. (2000) HIV-1 genome nuclear import is mediated by a central DNA flap. Cell 101, 173–185.

    PubMed  CrossRef  CAS  Google Scholar 

  49. Katzman, M. and Katz, R. A. (1999) Substrate recognition by retroviral integrases. Adv. Virus Res. 52, 371–395.

    PubMed  CrossRef  CAS  Google Scholar 

  50. Kaplan, A. H. and Swanstrom, R. (1991) Human immunodeficiency virus type 1 gag proteins are processed in two cellular compartments. Proc. Natl. Acad. Sci. USA 88, 4528–4532.

    PubMed  CrossRef  CAS  Google Scholar 

  51. Farson, D., Witt, R., McGuinness, R., et al. (2001) A new-generation stable inducible packaging cell line for lentiviral vectors. Hum. Gene Ther. 12, 981–997.

    PubMed  CrossRef  CAS  Google Scholar 

  52. Xu, K., Ma, H., McCown, T. J., Verma, I. M., and Kafri, T. (2001) Generation of a stable cell line producing high-titer self-inactivating lentiviral vectors. Mol. Ther. 3, 97–104.

    PubMed  CrossRef  CAS  Google Scholar 

  53. Seppen, J., Barry, S. C., Harder, B., and Osborne, W. R. (2001) Lentivirus administration to rat muscle provides efficient sustained expression of erythropoietin. Blood 98, 594–596.

    PubMed  CrossRef  CAS  Google Scholar 

  54. Baek, S. C., Lin, Q., Robbins, P. B., Fan, H., and Khavari, P. A. (2001) Sustainable systemic delivery via a single injection of lentivirus into human skin tissue. Hum. Gene Ther. 12, 1551–1558.

    PubMed  CrossRef  CAS  Google Scholar 

  55. Peng, K. W., Pham, L., Ye, H., et al. (2001) Organ distribution of gene expression after intravenous infusion of targeted and untargeted lentiviral vectors. Gene Ther. 8, 1456–1463.

    PubMed  CrossRef  CAS  Google Scholar 

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Federico, M. (2003). From Lentiviruses to Lentivirus Vectors. In: Federico, M. (eds) Lentivirus Gene Engineering Protocols. Methods in Molecular Biology™, vol 229. Humana Press. https://doi.org/10.1385/1-59259-393-3:3

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  • DOI: https://doi.org/10.1385/1-59259-393-3:3

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-091-5

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