Genetic and Neutralization Sensitivity of Diverse HIV-1 env Clones from Chronically Infected Patients in China
Genetic and Neutralization Sensitivity of Diverse HIV-1 env Clones from Chronically Infected Patients in China
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DOI：
10.1074/jbc.m111.224527
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发表时间：
2011-04-22
影响因子：
4.8
通讯作者：
Zhang, Linqi
中科院分区：
文献类型：
--
作者：
Shang, Hong;Han, Xiaoxu;Zhang, Linqi
随着HIV-1在中国继续从传统的高危人群向普通大众传播，其基因构成变得越来越复杂。然而，这些基因变化对病毒的生物学和中和敏感性的影响尚不清楚。目前的研究旨在描述2004年至2007年间在中国发现的HIV-1的遗传、生物学和中和敏感性。根据直接从感染患者中获得的107个全长包膜基因，我们发现这些病毒可分为三个主要的遗传群：CRF01_AE、B‘亚型和C/CRF07_BC/CRF08_BC/B’C亚型。基于活的env基因构建的假型病毒在介导病毒进入和对亚型特异性血浆池中和和广泛中和的单克隆抗体（bnmAb）的敏感性方面表现出实质性的差异。许多病毒对一种或多种bnmAb具有抗性，包括那些已知对来自中国以外的各种病毒具有高效力的病毒。序列和结构分析揭示了这些耐药病毒逃避bnmAb识别的几种机制。我们相信这些结果将有助于我们更好地理解遗传多样性对病毒中和敏感性的影响，并有助于设计能够产生与bnmAb相似的效力和广度的抗体的免疫原。
As HIV-1 continues to spread in China from traditional high risk populations to the general public, its genetic makeup has become increasingly complex. However, the impact of these genetic changes on the biological and neutralization sensitivity of the virus is unknown. The current study aims to characterize the genetic, biological, and neutralization sensitivity of HIV-1 identified in China between 2004 and 2007. Based on a total of 107 full-length envelope genes obtained directly from the infected patients, we found that those viruses fell into three major genetic groups: CRF01_AE, subtype B', and subtype C/CRF07_BC/CRF08_BC/B'C. Pseudotyped viruses built upon the viable env genes have demonstrated their substantial variability in mediating viral entry and in sensitivity to neutralization by subtype-specific plasma pools and broadly neutralizing monoclonal antibodies (bnmAb). Many viruses are resistant to one or more bnmAb, including those known to have high potency against diverse viruses from outside China. Sequence and structural analysis has revealed several mechanisms by which these resistant viruses escape recognition from bnmAb. We believe that these results will help us to better understand the impact of genetic diversity on the neutralizing sensitivity of the viruses and to facilitate the design of immunogens capable of eliciting antibodies with potency and breadth similar to those of bnmAb.