Abstract
Modification of dendritic cells (DCs) is a promising avenue for gene therapy purposes, given the versatility and the multiplicity of functions of these cells. In this study, we show that preincubation of monocyte-derived DCs with low amounts of non-infectious virion-like particles derived from the simian immunodeficiency virus (SIVMAC VLPs) increases up to 10-fold the efficiency of transduction by HIV-1 lentiviral vectors at low multiplicity of infections yielding up to 90% of transduced cells, in the absence of alterations of DCs behavior. This effect is restricted to DCs and specified by the viral accessory protein Vpx. Thus, preincubation with empty VLPs of SIVMAC can be used in transduction protocols to increase the efficacy of HIV-1-mediated modification of DCs.
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References
Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ et al. Immunobiology of dendritic cells. Annu Rev Immunol 2000; 18: 767–811.
Timares L, Douglas JT, Tillman BW, Krasnykh V, Curiel DT . Adenovirus-mediated gene delivery to dendritic cells. Methods Mol Biol 2004; 246: 139–154.
Ponnazhagan S, Mahendra G, Curiel DT, Shaw DR . Adeno-associated virus type 2-mediated transduction of human monocyte-derived dendritic cells: implications for ex vivo immunotherapy. J Virol 2001; 75: 9493–9501.
Mangeot PE, Duperrier K, Negre D, Boson B, Rigal D, Cosset FL et al. High levels of transduction of human dendritic cells with optimized SIV vectors. Mol Ther 2002; 5: 283–290.
Tan PH, Beutelspacher SC, Xue SA, Wang YH, Mitchell P, McAlister JC et al. Modulation of human dendritic-cell function following transduction with viral vectors: implications for gene therapy. Blood 2005; 105: 3824–3832.
Gruber A, Kan-Mitchell J, Kuhen KL, Mukai T, Wong-Staal F . Dendritic cells transduced by multiply deleted HIV-1 vectors exhibit normal phenotypes and functions and elicit an HIV-specific cytotoxic T-lymphocyte response in vitro. Blood 2000; 96: 1327–1333.
Kappes JC . Viral protein X. Curr Top Microbiol Immunol 1995; 193: 121–132.
Fletcher 3rd TM, Brichacek B, Sharova N, Newman MA, Stivahtis G, Sharp PM et al. Nuclear import and cell cycle arrest functions of the HIV-1 Vpr protein are encoded by two separate genes in HIV-2/SIV(SM). EMBO J 1996; 15: 6155–6165.
Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 1996; 272: 263–267.
von Gegerfelt AS, Liska V, Li PL, McClure HM, Horie K, Nappi F et al. Rev-independent simian immunodeficiency virus strains are nonpathogenic in neonatal macaques. J Virol 2002; 76: 96–104.
Goujon C, Jarrosson-Wuilleme L, Bernaud J, Rigal D, Darlix JL, Cimarelli A . Heterologous HIV-1 lentiviral vectors packaging an SIV-derived genome display a specific post-entry transduction defect in dendritic cells. J Virol 2003; 77: 9295–9304.
Acknowledgements
We are indebted to Dr Pavlakis for the SIV Gag construct. AC is financially supported by ANRS, Sidaction and NIH, and JLD from ANRS, and the TRIoH program of the EC.
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Goujon, C., Jarrosson-Wuillème, L., Bernaud, J. et al. With a little help from a friend: increasing HIV transduction of monocyte-derived dendritic cells with virion-like particles of SIVMAC. Gene Ther 13, 991–994 (2006). https://doi.org/10.1038/sj.gt.3302753
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DOI: https://doi.org/10.1038/sj.gt.3302753
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