J Virol：构造出一类抑制HIV感染细胞培养物的新蛋白

marine0425030

来自美国耶鲁大学癌症中心的研究人员开发出一种新类型的能够在细胞培养物中抑制HIV病毒感染的蛋白，从而可能为人们开发出治疗和预防这种导致艾滋病(AIDS)的HIV感染开启大门。相关研究结果于2012年7月18日在线发表在Journal of Virology期刊上。研究人员分离出6种由43到44个氨基酸组成的蛋白，它们能够抑制一种必需的HIV受体的总体表达，从而在实验室细胞培养物中阻断HIV感染。

这些蛋白是以来自导致奶牛患上疣的乳头瘤病毒中的一种蛋白为模型而构建出来的。这种牛乳头瘤病毒与导致宫颈癌和一些头颈癌的人乳头瘤病毒亲缘关系较近。

这些蛋白并不在自然条件下存在，这就提示着一种完全阻止AIDS的新策略。如果这些蛋白在人们体内发现是有活性的话，它们可能提供一种方法来阻止AIDS以及包括癌症在内的并发症。当然，将这项实验室发现应用于诊所还存在很多障碍，但是因为这些蛋白能够显著性地抑制HIV感染细胞培养物，所以它们应当还需进一步评估。

转自http://www.bioon.com/biology/sars/526844.shtml

Transmembrane protein aptamers that inhibit CCR5 expression and HIV co-receptor function

Elizabeth H. Scheideman1, Sara A. Marlatt1, Yanhua Xie1, Yani Hu2, Richard E. Sutton2,5 and Daniel DiMaio

We have exploited the ability of transmembrane domains to engage in highly-specific protein-protein interactions to construct a new class of small proteins that inhibit HIV infection. By screening a library encoding hundreds of thousands of artificial transmembrane proteins with randomized transmembrane domains (“traptamers”), we isolated six 44- or 45-amino acid proteins with completely different transmembrane sequences that inhibited cell-surface and total expression of the HIV co-receptor CCR5. The traptamers inhibited transduction of human T-cells by HIV reporter viruses pseudotyped with R5-tropic gp120 envelope proteins, but had minimal effects on reporter viruses with X4-tropic gp120. Optimization of two traptamers significantly increased their activity and resulted in greater than 95% inhibition of R5-tropic reporter virus transduction, without inhibiting expression of CD4, the primary HIV receptor, or CXCR4, another HIV co-receptor. In addition, traptamers inhibited transduction mediated by a mutant R5-tropic gp120 protein resistant to Maraviroc, a small molecule CCR5 inhibitor, and they dramatically inhibited replication of an R5-tropic laboratory strain of HIV in a multi-cycle infection assay. Genetic experiments suggested that the active traptamers specifically interacted with the transmembrane domains of CCR5 and that some of the traptamers interacted with different portions of CCR5. Thus, we have constructed multiple proteins not found in nature that interfere with CCR5 expression and inhibit HIV infection. These proteins may be valuable tools to probe the organization of the transmembrane domains of CCR5 and their relationship to its biological activities, and they may serve as starting points to develop new strategies to inhibit HIV infection.

原文链接http://jvi.asm.org/content/early/2012/07/12/JVI.00910-12.long