Department of Microbiology, Immunology, and Molecular Genetics, UCLA, United States.
Virology. 2013 Jan 5;435(1):81-91. doi: 10.1016/j.virol.2012.09.043.
HIV-1 envelope (Env) uses CD4 and a coreceptor (CCR5 and/or CXCR4) for viral entry. The efficiency of receptor/coreceptor mediated entry has important implications for HIV pathogenesis and transmission. The advent of CCR5 inhibitors in clinical use also underscores the need for quantitative and predictive tools that can guide therapeutic management. Historically, measuring the efficiency of CD4/CCR5 mediated HIV entry has relied on surrogate and relatively slow throughput assays that cannot adequately capture the full spectrum of Env phenotypes. In this review, we discuss the details of the Affinofile receptor affinity profiling system that has provided a quantitative and higher throughput method to characterize viral entry efficiency as a function of CD4 and CCR5 expression levels. We will then review how the Affinofile system has been used to reveal the distinct pathophysiological properties associated with Env entry phenotypes and discuss potential shortcomings of the current system.
HIV-1 包膜 (Env) 利用 CD4 和辅助受体 (CCR5 和/或 CXCR4) 进入病毒。受体/辅助受体介导的进入效率对 HIV 的发病机制和传播有重要影响。CCR5 抑制剂在临床应用中的出现也强调了需要定量和预测性工具来指导治疗管理。从历史上看，测量 CD4/CCR5 介导的 HIV 进入的效率依赖于替代物和相对较慢的高通量测定，不能充分捕获 Env 表型的全部范围。在这篇综述中，我们讨论了 Affinofile 受体亲和力分析系统的细节，该系统提供了一种定量和更高通量的方法来描述 CD4 和 CCR5 表达水平作为病毒进入效率的函数。然后，我们将回顾 Affinofile 系统如何用于揭示与 Env 进入表型相关的独特病理生理学特性，并讨论当前系统的潜在缺陷。
