SIVMAC Vpx improves the transduction of dendritic cells with nonintegrative HIV-1-derived vectors.
Lentiviral vector (LV)-mediated gene therapy bears an intrinsic risk of insertional mutagenesis following integration into the host genome. Nonintegrative LVs may offer an alternative avenue at least in nondividing cells where episomal viral DNA persists stably. Owing to their central role in immune system functions, differentiated dendritic cells (DCs) offer an interesting cell target for these vectors. We have previously described that the transduction of DCs with wild-type HIV-1-derived vectors can be considerably improved by providing DCs with noninfectious virion-like particles (VLPs) carrying Vpx (Vpx-VLPs), a nonstructural protein coded by members of the SIV(SM)/HIV-2 lineage that removes a specific restriction to lentiviral infection in these cells. Here, we describe that the transduction efficiency of DCs with nonintegrative HIV-1 vectors can also be improved via Vpx-VLPs that promote the accumulation of complete and episomal viral DNA. In this setting, Vpx increases both the number of transduced cells and the levels of transgene expression. Thus, these results describe a simple procedure by which transduction of differentiated DCs can be achieved at low viral inputs with safer LVs to improve both the number of transduced cells and the levels of transgene expression.
Berger
G
G
LaboRetro, Department of Human Virology, Ecole Normale Supérieure de Lyon, Lyon, France.
Goujon
C
C
Darlix
J-L
JL
Cimarelli
A
A
D002478:Cells, Cultured; D003713:Dendritic Cells / Q000821:virology*; D015870:Gene Expression; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D014161:Transduction, Genetic / Q000379:methods*; D019076:Transgenes; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics*; D014771:Virion / Q000235:genetics; D016662:Virus Integration
C074286:VPX protein, Human immunodeficiency virus 2; D054334:Viral Regulatory and Accessory Proteins; D049452:Green Fluorescent Proteins