The efficiency of simian foamy virus vector type-1 (SFV-1) in nondividing cells and in human PBLs

Current retroviral vectors based on murine leukemia virus (MuLV) are unable to efficiently transduce nondividing cells. Lentiviruses, such as the huma n immunodeficiency virus 1 (HIV-1) are efficient at transducing nondividing , growth-arrested. and post-mitotic cells, but due to complex safety consid erations, they may have limited potential for human clinical gene transfer. For this reason, alternatives to MuLV and HIV-1 vectors need to be explore d. In this paper, we have found that simian foamy virus vector (SFV-1) cont aining a CMV-LacZ expression cassette is able to efficiently transduce mult iple cell types of various species that include epithelial, lymphoid, and h ematopoietic-derived human cell lines and fibroblast cell lines of several species. Previously it was reported that foamy virus replication is cell cy cle dependent (P. D. Bieniasz, R. A. Weiss, and M. O. McClure, 1995. J. Vir ol. 69, 7295-7299). However, others studies demonstrated nuclear import of viral DNA in arrested cells (A. Saibi, F. Puvion-Dutilleul, M. Schmid, J. P eries, and H. d. The 1997 J. Virol. 71, 1155-1161). Here, we show efficient LacZ transduction by SFV-1 Vectors in several chemically arrested cell lin es and terminally differentiated human neurons. SFV-1 vector can transduce cell lines arrested in G1/S phase of the cell cycle by aphidicolin treatmen t with similar efficiencies to that of dividing cells. The terminally diffe rentiated human neural cell line, NT2N, was transduced with 30-50% efficien cy, corroborating our data obtained with the arrested cell lines. To furthe r examine whether the SFV-1 vector can efficiently deliver a gene into clin ically important cells for gene therapy, we transduced primary human periph eral blood cells (PBLs) in the presence and absence of phytohemagglutanin ( PHA) stimulation. We observed 81% transduction efficiency in non-stimulated PBLs and 87% in PHA-srimulated PBLs with vector infection carried out twic e in 8 hours intervals at a multiplicity of infection of 1, Together, these data indicate that SFV-1 based retroviral vectors may provide a safe, effi cient alternative to current onco- and lentiviral vectors for gene transfer in cells from a broad spectrum of lineages across species boundaries. (C) 2001 Academic Press.