Expression of a protective gene-prolongs survival of T cells in human immunodeficiency virus-infected patients.
Expression of a protective gene-prolongs survival of T cells in human immunodeficiency virus-infected patients.
复制标题
保护性基因的表达可延长人类免疫缺陷病毒感染患者 T 细胞的存活时间。
DOI：
10.1073/pnas.93.7.2889
复制
发表时间：
1996
影响因子：
11.1
通讯作者：
Nabel,GJ
中科院分区：
文献类型：
--
作者：
Woffendin,C;Ranga,U;Yang,Z;Xu,L;Nabel,GJ
获得性免疫缺陷综合症（艾滋病）对传统药物治疗的耐药性促使人们寻找治疗这种疾病的替代疗法。一种潜在的方法是提供对病毒复制的遗传抗性，以延长潜伏期。这一策略需要确定有效的抗病毒基因，以延长人类免疫缺陷病毒（HIV）感染者体内T细胞的存活时间。我们报告了一项人类研究的结果，该研究旨在确定遗传干预是否可以延长hiv感染者体内T细胞的存活时间。基因转移在富集的CD4+细胞中进行，质粒表达载体编码抑制性Rev蛋白Rev M10或缺失突变对照物deltaRev M10，由金微粒传递。分别转染每种载体的自体细胞返回给每位患者，并评估转基因细胞的毒性、基因表达和存活。在体外实验中，表达Rev M10的细胞比携带deltaRev M10的细胞更能抵抗HIV感染。在hiv感染的受试者中，Rev M10转导的细胞比deltaRev M10对照组表现出更优的存活。因此，Rev M10可以作为一种特异性的细胞内抑制剂，延长hiv -1感染者的t细胞存活时间，并可能作为一种分子遗传干预手段，有助于治疗艾滋病。
The resistance of acquired immunodeficiency syndrome (AIDS) to traditional drug therapy has prompted a search for alternative treatments for this disease. One potential approach is to provide genetic resistance to viral replication to prolong latency. This strategy requires the definition of effective antiviral genes that extend the survival of T cells in human immunodeficiency virus (HIV)-infected individuals. We report the results of a human study designed to determine whether a genetic intervention can prolong the survival of T cells in HIV-infected individuals. Gene transfer was performed in enriched CD4+ cells with plasmid expression vectors encoding an inhibitory Rev protein, Rev M10, or a deletion mutant control, deltaRev M10, delivered by gold microparticles. Autologous cells separately transfected with each of the vectors were returned to each patient, and toxicity, gene expression, and survival of genetically modified cells were assessed. Cells that expressed Rev M10 were more resistant to HIV infection than those with deltaRev M10 in vitro. In HIV-infected subjects, Rev M10-transduced cells showed preferential survival compared to deltaRev M10 controls. Rev M10 can therefore act as a specific intracellular inhibitor that can prolong T-cell survival in HIV-1-infected individuals and potentially serve as a molecular genetic intervention which can contribute to the treatment of AIDS.