Duan L, Zhu M, Bagasra O, Pomerantz R J
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Hum Gene Ther. 1995 Dec;6(12):1561-73. doi: 10.1089/hum.1995.6.12-1561.
Genetic therapy offers a potentially promising approach with which to combat human immunodeficiency virus type 1 (HIV-1) infections. Several modalities, using protein- and RNA-based systems, have recently been shown to inhibit HIV-1 replication. A single-chain variable fragment (SFv), constructed from the cDNA of a monoclonal antibody to the HIV-1 regulatory protein Rev, has been demonstrated to potently inhibit HIV-1 replication, when expressed intracellularly in an epithelial cell-line (HeLa-CD4). Murine retroviral shuttle vectors, which express the anti-Rev SFv moiety, have now been constructed. HIV-1 infection was dramatically inhibited in human T-lymphocytic cell-lines, CEM and Sup-T1, transduced with these anti-Rev SFv-expressing vectors. This resistance to high levels of HIV-1 expression was demonstrated in both mixed populations and clones of these cells. Of further potential clinical significance, HIV-1 infection was also potently inhibited in human peripheral blood mononuclear cells (PBMC), transduced with retroviral vectors expressing the anti-Rev SFv molecule. These data suggest that intracellular expression of anti-Rev SFvs, or related approaches, may be utilized as genetic therapy, or intracellular immunization, for HIV-1 infections in vivo.
基因治疗为对抗人类免疫缺陷病毒1型（HIV-1）感染提供了一种潜在的有前景的方法。最近已证明，几种使用基于蛋白质和RNA系统的方法可抑制HIV-1复制。从针对HIV-1调节蛋白Rev的单克隆抗体的cDNA构建的单链可变片段（SFv），当在一种上皮细胞系（HeLa-CD4）中进行细胞内表达时，已被证明能有效抑制HIV-1复制。现已构建出表达抗Rev SFv部分的鼠逆转录病毒穿梭载体。在用这些表达抗Rev SFv的载体转导的人T淋巴细胞系CEM和Sup-T1中，HIV-1感染受到显著抑制。在这些细胞的混合群体和克隆中均证实了对高水平HIV-1表达的抗性。更具潜在临床意义的是，在用表达抗Rev SFv分子的逆转录病毒载体转导的人外周血单个核细胞（PBMC）中，HIV-1感染也受到有效抑制。这些数据表明，抗Rev SFv的细胞内表达或相关方法可作为针对体内HIV-1感染的基因治疗或细胞内免疫。
