Intracellular immunization against HIV-1 infection of human T lymphocytes: Utility of anti-rev single-chain variable fragments
Intracellular immunization against HIV-1 infection of human T lymphocytes: Utility of anti-rev single-chain variable fragments
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DOI：
10.1089/hum.1995.6.12-1561
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发表时间：
1995-12-01
影响因子：
4.2
通讯作者：
Pomerantz, RJ
中科院分区：
文献类型：
--
作者：
Duan, LX;Zhu, MH;Pomerantz, RJ
基因治疗提供了一个潜在的有前途的方法，与人类免疫缺陷病毒1型（HIV-1）感染的斗争。最近已经证明，使用基于蛋白质和RNA的系统的几种方式可以抑制HIV-1复制。由HIV-1调节蛋白Rev的单克隆抗体的cDNA构建的单链可变区片段（SFv），当在上皮细胞系（HeLa-CD 4）中胞内表达时，已被证明有效地抑制HIV-1复制。现在已经构建了表达抗Rev SFv部分的鼠逆转录病毒穿梭载体。HIV-1感染显着抑制人类T淋巴细胞系，CEM和Sup-T1，这些抗Rev SFv表达载体转导。这种对高水平HIV-1表达的抗性在这些细胞的混合群体和克隆中均得到证实。具有进一步潜在临床意义的是，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核细胞（PBMC）中，HIV-1感染也被有效抑制。这些数据表明，抗Rev SFvs的细胞内表达或相关方法可用作体内HIV-1感染的基因治疗或细胞内免疫。
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.