EVALUATION OF RETROVIRAL VECTORS BASED ON THE GIBBON APE LEUKEMIA-VIRUS

The gibbon ape leukemia viruses (GaLVs) are primate-derived C-type ret roviruses with a broad host range. Using an infectious, full-length cl one of the GaLV SEATO strain, we have determined that this virus repli cates efficiently in 13 of 17 human cell lines tested. In fact, the SB lymphoblast cell line, while resistant to infection by wild-type amph otropic mouse leukemia virus (A-MLV), was infected by GaLV-SEATO. We c onstructed vectors containing GaLV components and compared the perform ance of genomes containing an enhancer and promoter derived either fro m the SEATO or SF strains of GaLV. The GaLV vector genomes were packag ed in a Moloney (Mo)MLV core with either an A-MLV or GaLV SEATO envelo pe. We found that, in some cases, the vector genome appeared to be cri tical in obtaining optimal infection. For example, vectors with a GaLV SF-based genome infected the human HL60 cell line, whereas vectors wi th a GaLV SEATO-based genome did not We also found that most, but not all, of the human cell lines tested were more susceptible to vectors p ackaged with the GaLV SEATO than A-MLV envelope. The source of the vir al core was also important, in that some human cells appeared suscepti ble to infection only with GaLV genomes packaged in particles composed of a GaLV core and envelope. Our results show that GaLV-based package able genomes can be expressed in target cells not efficiently infected by vectors containing MoMLV-based genomes. These results suggest that judicious combinations of retroviral genomes and structural component s can significantly improve gene transfer into human cells.