HIV-1 gp120上N332聚糖占据的概率调节对广泛中和抗体的敏感性。
Probability of N332 glycan occupancy on HIV-1 gp120 modulates sensitivity to broadly neutralizing antibodies.
作者信息
van den Kerkhof Tom L G M, van Gils Marit J, Boeser-Nunnink Brigitte D, Burger Judith A, Schuitemaker Hanneke, Sanders Rogier W
机构信息
aDepartment of Medical Microbiology bDepartment of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam cJanssen Pharmaceuticals, Leiden, The Netherlands dDepartment of Microbiology and Immunology, Weill Medical College, Cornell University, New York City, New York, USA.
出版信息
AIDS. 2016 Sep 10;30(14):2179-84. doi: 10.1097/QAD.0000000000001177.
OBJECTIVE(S): The glycan shield of the HIV-1 envelope glycoprotein complex (Env), in particular the glycan at position 332 in gp120, is frequently targeted by broadly neutralizing antibodies (bNAbs) isolated from HIV-1-infected individuals. We investigated the role of the second amino acid position of the N332 glycosylation motif Asn-X-Ser in HIV-1 evolution and neutralization sensitivity.
DESIGN AND METHODS
Viral variants harbouring glycosylation motifs with different probabilities of glycan occupancy were tested for their sensitivity to a subset of N332-dependent bNAbs. Furthermore, longitudinal Env sequences of 37 HIV-1 infected individuals were used to analyse the evolution of the N332 glycosylation motif within these individuals. Finally, early Env sequences from 31 historical and 21 contemporaneous seroconverters were compared to analyse this evolution on a population level.
RESULTS
Viral variants with a higher probability of N332 occupancy were more sensitive to neutralization by some N332-dependent bNAbs. Furthermore, the longitudinal analyses revealed an increase in probability of glycan occupancy of the N332 site over time, both within patients, and at the population level over the course of 20 years of HIV-1 epidemic.
CONCLUSIONS
These observations suggest that modulation of N332 glycan occupancy by the second amino acid position of the canonical glycosylation motif Asn-X-Ser plays a previously unappreciated role in viral escape from immune responses, and should be considered in Env-based vaccine design.
目的
HIV-1包膜糖蛋白复合物（Env）的聚糖屏蔽，特别是gp120中332位的聚糖，经常被从HIV-1感染个体中分离出的广谱中和抗体（bNAbs）靶向。我们研究了N332糖基化基序Asn-X-Ser的第二个氨基酸位置在HIV-1进化和中和敏感性中的作用。
设计与方法
测试携带具有不同聚糖占据概率的糖基化基序的病毒变体对一组N332依赖性bNAbs的敏感性。此外，使用37名HIV-1感染个体的Env纵向序列来分析这些个体中N332糖基化基序的进化。最后，比较了31名历史血清转化者和21名同期血清转化者的早期Env序列，以在群体水平上分析这种进化。
结果
N332占据概率较高的病毒变体对某些N332依赖性bNAbs的中和更敏感。此外，纵向分析显示，在患者体内以及在HIV-1流行20年的过程中，在群体水平上，N332位点的聚糖占据概率随时间增加。
结论
这些观察结果表明，经典糖基化基序Asn-X-Ser的第二个氨基酸位置对N332聚糖占据的调节在病毒逃避免疫反应中发挥了以前未被认识到的作用，并且在基于Env的疫苗设计中应予以考虑。
Zotero 插件