Lodge R, Subbramanian R A, Forget J, Lemay G, Cohen E A
Département de Microbiologie et Immunologie, Université de Montréal, Québec, Canada.
Gene Ther. 1998 May;5(5):655-64. doi: 10.1038/sj.gt.3300646.
Human immunodeficiency virus (HIV) infection ultimately leads to the destruction of the CD4+ lymphocyte subset and the onset of AIDS. In recent years, several gene therapy procedures making use of retroviral vectors that selectively target HIV susceptible cells have been proposed in order to interfere with HIV productive infection. However, the HIV glycoproteins' inability to be incorporated in other heterologous retroviruses considerably limits true HIV cell tropism of such vectors. We now report 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 specific to CD4+ cells when HeLaCD4 cells or peripheral blood lymphocytes (PBLs) were infected with these pseudotyped MuLV virus vectors. In contrast, MuLV viruses harboring amphotropic MuLV envelope glycoproteins displayed a broad and nonspecific infection of PBL subpopulations. This new approach, taking advantage of the ability of truncated HIV envelope glycoproteins to be incorporated into heterologous retroviral particles, may foreseeably be used in future interventions based on the coordinated delivery of therapeutic gene products specifically to cell types susceptible to HIV infection.
人类免疫缺陷病毒（HIV）感染最终会导致CD4+淋巴细胞亚群的破坏以及艾滋病的发作。近年来，为了干扰HIV的有效感染，人们提出了几种利用逆转录病毒载体选择性靶向HIV易感细胞的基因治疗方法。然而，HIV糖蛋白无法整合到其他异源逆转录病毒中，这在很大程度上限制了此类载体真正的HIV细胞嗜性。我们现在报告使用携带截短形式HIV糖蛋白的鼠白血病病毒（MuLV）病毒颗粒进行特异性基因传递。当用这些假型MuLV病毒载体感染HeLaCD4细胞或外周血淋巴细胞（PBL）时，报告基因lacZ基因转移被确定对CD4+细胞具有适当的特异性。相比之下，携带嗜异性MuLV包膜糖蛋白的MuLV病毒对PBL亚群表现出广泛且非特异性的感染。这种利用截短的HIV包膜糖蛋白整合到异源逆转录病毒颗粒中的能力的新方法，有望在未来基于将治疗性基因产物特异性递送至易受HIV感染的细胞类型的干预措施中得到应用。
