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噬菌体与人类免疫缺陷病毒1型:从展示到相互作用

Phages and HIV-1: from display to interplay.

作者信息

Delhalle Sylvie, Schmit Jean-Claude, Chevigné Andy

机构信息

Laboratory of Retrovirology, CRP-Sante, 84, Val Fleuri, L-1526 Luxembourg, Luxembourg.

Service National des Maladies Infectieuses, Centre Hospitalier Luxembourg, 4, rue E. Barblé, L-1210 Luxembourg, Luxembourg.

出版信息

Int J Mol Sci. 2012;13(4):4727-4794. doi: 10.3390/ijms13044727. Epub 2012 Apr 13.

Abstract

The complex hide-and-seek game between HIV-1 and the host immune system has impaired the development of an efficient vaccine. In addition, the high variability of the virus impedes the long-term control of viral replication by small antiviral drugs. For more than 20 years, phage display technology has been intensively used in the field of HIV-1 to explore the epitope landscape recognized by monoclonal and polyclonal HIV-1-specific antibodies, thereby providing precious data about immunodominant and neutralizing epitopes. In parallel, biopanning experiments with various combinatorial or antibody fragment libraries were conducted on viral targets as well as host receptors to identify HIV-1 inhibitors. Besides these applications, phage display technology has been applied to characterize the enzymatic specificity of the HIV-1 protease. Phage particles also represent valuable alternative carriers displaying various HIV-1 antigens to the immune system and eliciting antiviral responses. This review presents and summarizes the different studies conducted with regard to the nature of phage libraries, target display mode and biopanning procedures.

摘要

人类免疫缺陷病毒1型(HIV-1)与宿主免疫系统之间复杂的捉迷藏游戏阻碍了高效疫苗的研发。此外,该病毒的高变异性妨碍了小分子抗病毒药物对病毒复制的长期控制。20多年来,噬菌体展示技术一直在HIV-1领域得到广泛应用,以探索单克隆和多克隆HIV-1特异性抗体所识别的表位图谱,从而提供有关免疫显性表位和中和表位的宝贵数据。与此同时,针对病毒靶点以及宿主受体开展了各种组合或抗体片段文库的淘选实验,以鉴定HIV-1抑制剂。除了这些应用,噬菌体展示技术还被用于表征HIV-1蛋白酶的酶促特异性。噬菌体颗粒也是向免疫系统展示各种HIV-1抗原并引发抗病毒反应的有价值的替代载体。本综述介绍并总结了有关噬菌体文库性质、靶点展示模式和淘选程序的不同研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/3344243/2d4459e50d3f/ijms-13-04727f1.jpg

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