SELECTIVE KILLING OF HIV-INFECTED CELLS BY RECOMBINANT HUMAN CD4-PSEUDOMONAS EXOTOXIN HYBRID PROTEIN
SELECTIVE KILLING OF HIV-INFECTED CELLS BY RECOMBINANT HUMAN CD4-PSEUDOMONAS EXOTOXIN HYBRID PROTEIN
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DOI：
10.1038/335369a0
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发表时间：
1988-09-22
期刊：
影响因子：
64.8
通讯作者：
BERGER, EA
中科院分区：
文献类型：
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作者：
CHAUDHARY, VK;MIZUKAMI, T;BERGER, EA
据预测，在缺乏有效治疗的情况下，大多数感染人类免疫缺陷病毒（HIV）的个体将发展为获得性免疫缺陷综合征（AIDS），并最终死于机会性微生物感染、恶性肿瘤和病毒的直接致病作用的组合1 -3。抗病毒药物、免疫调节剂和特定HIV功能的抑制剂正在作为潜在的治疗方法进行测试，以缓解高发病率和死亡率4。另一种治疗概念涉及开发靶向杀死HIV感染细胞的细胞毒性剂。在这里，我们描述了大肠杆菌中产生的重组蛋白的纯化和表征，该重组蛋白含有与假单胞菌外毒素A的活性区连接的人CD 4分子的HIV结合部分。这种杂合蛋白显示出对表达HIV包膜糖蛋白的细胞的选择性毒性，因此代表了用于治疗AIDS的有希望的新型治疗剂。
It is projected that in the absence of effective therapy, most individuals infected with human immunodeficiency virus (HIV) will develop acquired immune deficiency syndrome (AIDS) and ultimately succumb to a combination of opportunistic microbial infections, malignancies and direct pathogenic effects of the virus1–3. Anti-viral agents, immunomodulators, and inhibitors of specific HIV functions are being tested as potential treatments to alleviate the high morbidity and mortality4. An alternative therapeutic concept involves the development of cytotoxic agents that are targeted to kill HIV-infected cells. Here we describe the purification and characterization of a recombinant protein produced inEscherichia colithat contains the HIV-binding portion of the human CD4 molecule linked to active regions ofPseudomonasexotoxin A. This hybrid protein displays selective toxicity toward cells expressing the HIV envelope glycoprotein and thus represents a promising novel therapeutic agent for the treatment of AIDS.