Abstract
Lentiviral vectors are promising tools for gene transfer (1–4). Like oncoret-roviral vectors, they offer the unique advantage of stably integrating into the genome of the host cell, thus providing the basis for sustained gene expression. In contrast to the classical oncoretrovirus derived vectors, lentiviral vectors are highly efficient at infection of nondividing cells because of the presence of nuclear localization signals on several virion associated proteins, which include matrix (MA), viral protein R (VPR), and integrase (IN) in the case of human immunodeficiency virus type-one (HIV-1) (5).
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Klimatcheva, E., Rosenblatt, J. D., and Planelles, V. (1999) Lentiviral vectors and gene therapy. Front. Biosci. 4, D481–S496.
Stripecke, R., Cardoso, A. A., Pepper, K. A., et al. (2000) Lentiviral vectors for efficient delivery of CD80 and granulocyte-macrophage-colony-stimulating factor in human acute lymphoblastic leukemia and acute myeloid leukemia cells to induce antileukemic immune responses. Blood 96,1317–1326.
Trono, D. (2000) Lentiviral vectors: turning a deadly foe into a therapeutic agent. Gene Ther. 7, 20–23.
Vigna, E. and Naldini, L. (2000) Lentiviral vectors: excellent tools for experimental gene transfer and promising candidates for gene therapy. J. Gene Med. 2, 308–316.
Bukrinsky, M. I. and Haffar, O. K. (1999) HIV-1 nuclear import: in search of a leader. Front. Biosci. 4, D772–D781.
Akkina, R. K., Walton, R. M., Chen, M. L., Li, Q. X., Planelles, V., et al. (1996) High-efficiency gene transfer into CD34+cells with a human immunodeficiency virus type 1-based retroviral vector pseudotyped with vesicular stomatitis virus envelope glycoprotein G. J. Virol. 70, 2581–2585.
Burns, J. C., Friedmann, T., Driever, W., Burrascano, M., and Yee, J. K. (1993) Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells. Proc. Natl. Acad. Sci. USA 90, 8033–8037.
Yee, J. K., Friedmann, T., and Burns, J. C. (1994) Generation of high-titer pseudotyped retroviral vectors with very broad host range. Meth. Cell Biol. 43 Pt A, 99–112.
Landau, N. R., Page, K. A., and Littman, D. R. (1991) Pseudotyping with human T-cell leukemia virus type I broadens the human immunodeficiency virus host range. J. Virol. 65, 162–169.
Page, K. A., Landau, N. R., and Littman, D. R. (1990) Construction and use of a human immunodeficiency virus vector for analysis of virus infectivity. J. Virol. 64, 5270–5276.
Kobinger, G. P., Weiner, D. J., Yu, Q. C., and Wilson, J. M. (2001) Filovirus-pseudotyped lentiviral vector can efficiently and stably transduce airway epithelia in vivo. Nat. Biotechnol. 19, 225–230.
Reiser, J. (2000) Production and concentration of pseudotyped HIV-1-based gene transfer vectors. Gene Ther. 7, 910–913.
Gatignol, A. and Jeang, K. T. (2000) Tat as a transcriptional activator and a potential therapeutic target for HIV-1. Adv. Pharmacol. 48, 209–227.
Taube, R., Fujinaga, K., Wimmer, J., Barboric, M., and Peterlin, B. M. (1999) Tat transactivation: a model for the regulation of eukaryotic transcriptional elongation. Virology 264, 245–253.
Watson, K. and Edwards, R. J. (1999) HIV-1-trans-activating (Tat) protein: both a target and a tool in therapeutic approaches. Biochem. Pharmacol. 58,1521–1528.
Kjems, J. and Askjaer, P. (2000) Rev protein and its cellular partners. Adv. Pharmacol. 48, 251–298.
Hope, T. J. (1999) The ins and outs of HIV Rev. Arch. Biochem. Biophys. 365, 186–191.
Cullen, B. R. and Greene, W. C. (1989) Regulatory pathways governing HIV-1 replication. Cell 58,423–426.
Cullen, B. R. (1998) HIV-1 auxiliary proteins: making connections in a dying cell. Cell 93, 685–692.
Neumann, M., Harrison, J., Saltarelli, M., et al. (1994) Splicing variability in HIV type 1 revealed by quantitative RNA polymerase chain reaction. AIDS Res. Hum. Retroviruses 10,1531–1542.
Pavlakis, G. N., Schwartz, S., D’Agostino, D., and Felber, B. (1992) Structure, splicing, and regulation of expression of HIV-1: a model for the general organization of lentiviruses and other complex retroviruses, in AIDS Research Reviews (Koff, W. C., Kennedy, R. C., and Wong-Staal, F., eds.), Marcel Dekker, New York, pp. 41–63.
Fischer, U., Meyer, S., Teufel, M., Heckel, C., Luhrmann, R., and Rautmann, G. (1994) Evidence that HIV-1 Rev directly promotes the nuclear export of unspliced RNA. EMBO J. 13,4105–4112.
Cullen, B. R. (1998) Retroviruses as model systems for the study of nuclear RNA export pathways. Virology 249, 203–210.
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.
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.
Nakajima, T., Nakamaru, K., Ido, E., Terao, K., Hayami, M., and Hasegawa, M. (2000) Development of novel simian immunodeficiency virus vectors carrying a dual gene expression system. Hum. Gene Ther. 11,1863–1874.
Zhu, Y., Gelbard, H. A., Roshal, M., Pursell, S., Jamieson, B. D., and Planelles, V. (2001) Comparison of cell cycle arrest, transactivation, and apoptosis induced by the simian immunodeficiency virus SIVagm and human immunodeficiency virus type 1 vpr genes. J. Virol. 75, 3791–3801.
Zhu, Y., Feuer, G., Day, S. L., Wrzesinski, S., and Planelles, V. (2001) Multigene lentivirus vectors based on differential splicing and translational control. Mol. Ther. 4, 375–382.
Ross, T. M. (2001) Using death to one’s advantage: HIV modulation of apoptosis. Leukemia 15,332–341.
Krzyzowska, M., Schollenberger, A., and Niemialtowski, M. G. (2000) How human immunodeficiency viruses and herpesviruses affect apoptosis. Acta. Virol. 44, 203–210.
Roshal, M., Zhu, Y., and Planelles, V. (2001) Apoptosis in AIDS. Apoptosis 6, 103–116.
Gibellini, D., Re, M. C., Ponti, C., et al. (2001) HIV-1 Tat protects CD4+Jurkat T lymphoblastoid cells from apoptosis mediated by TNF-related apoptosis-inducing ligand. Cell Immunol. 207, 89–99.
An, D. S., Morizono, K., Li, Q. X., Mao, S. H., Lu, S., and Chen, I. S. (1999) An inducible human immunodeficiency virus type 1 (HIV-1) vector which effectively suppresses HIV-1 replication. J. Virol. 73, 7671–7677.
White, S. M., Renda, M., Nam, N. Y., et al. (1999) Lentivirus vectors using human and simian immunodeficiency virus elements. J. Virol. 73, 2832–2840.
Naldini, L., Blomer, U., Gallay, P., et al. (1996) In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272, 263–267.
Planelles, V., Haislip, A., Withers-Ward, E. S., et al. (1995) A new reporter system for detection of retroviral infection. Gene Ther. 2, 369–376.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Humana Press Inc.
About this protocol
Cite this protocol
Zhu, Y., Planelles, V. (2003). A Multigene Lentiviral Vector System Based on Differential Splicing. In: Machida, C.A. (eds) Viral Vectors for Gene Therapy. Methods in Molecular Medicine™, vol 76. Humana Press. https://doi.org/10.1385/1-59259-304-6:433
Download citation
DOI: https://doi.org/10.1385/1-59259-304-6:433
Publisher Name: Humana Press
Print ISBN: 978-1-58829-019-9
Online ISBN: 978-1-59259-304-0
eBook Packages: Springer Protocols