Construction and molecular analysis of gene transfer systems derived from bovine immunodeficiency virus

Because lentiviruses are able to infect nondividing cells, these viruses mi ght be utilized in gene therapy applications where the target cell does not divide. However, it has been suggested that the introduction of primate le ntivirus sequences, particularly those of human immunodeficiency virus, int o human cells may pose a health risk for the patient. To avoid this concern , we have constructed gene transfer systems based on a nonprimate lentiviru s, bovine immunodeficiency virus. A panel of vectors and packaging construc ts was generated and analyzed in a transient expression system for virion p roduction and maturation, vector expression and encapsidation, and envelope protein pseudotyping. Virion preparations were also analyzed for transduct ion efficiency in a panel of human and nonhuman primary cells and immortali zed cell lines. The virion preparations transduced most of the target cell types, with efficiencies up to 90% and with titers of unconcentrated virus up to 5 x 10(5) infectious doses/ml. In addition, infection of nondividing human cells, including unstimulated hematopoietic stem cells and irradiated endothelial cells, was observed.