MULV-BASED VECTORS PSEUDOTYPED WITH TRUNCATED HIV GLYCOPROTEINS MEDIATE SPECIFIC GENE-TRANSFER IN CD4(-BLOOD LYMPHOCYTES() PERIPHERAL)

Human immunodeficiency virus (HIV) infection ultimately leads to the d estruction of the CD4(+) lymphocyte subset and onset of AIDS. In recen t years, several gene therapy procedures making use of retroviral vect ors that selectively target HIV susceptible cells have been proposed i n to interfere with HIV productive infection. However, the HIV glycopr oteins' inability to be incorporated in other heterologous retroviruse s considerably limits true HIV cell tropism of such vectors. We now re port the use of murine leukemia virus (MuLV) viral particles harboring a truncated form of the HIV glycoprotein for specific gene delivery. Reporter lacZ gene transfer was determined to be appropriately specifi c to CD4(+) cells when HeLaCD4 cells or peripheral blood lymphocytes ( PBLs) were infected with these pseudotyped MuLV virus vectors. In cont rast, MuLV viruses harboring amphotropic MuLV envelope glycoproteins d isplayed a broad and nonspecific infection of PBL subpopulations. This new approach, taking advantage of the ability of truncated HIV envelo pe glycoproteins to be incorporated into heterologous retroviral parti cles, may foreseeably be used in future interventions based on the coo rdinated delivery of therapeutic gene products specifically to cell ty pes susceptible to HIV infection.