Highly conserved HIV-1 gp120 glycans proximal to CD4-binding region affect viral infectivity and neutralizing antibody induction
Highly conserved HIV-1 gp120 glycans proximal to CD4-binding region affect viral infectivity and neutralizing antibody induction
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靠近 CD4 结合区的高度保守的 HIV-1 gp120 聚糖影响病毒感染性和中和抗体诱导。
DOI：
10.1016/j.virol.2011.11.023
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发表时间：
2012-02-05
期刊：
影响因子：
3.7
通讯作者：
Hu, Qinxue
中科院分区：
文献类型：
--
作者：
Huang, Xin;Jin, Wei;Hu, Qinxue
糖基化在gp 120结构和HIV-1免疫逃避中起重要作用。在本研究中，我们将去糖基化引入从精液中克隆的R5 env MWS 2的24个N-连接的糖基化位点，并系统地分析了对感染性、抗原性、免疫原性和对进入抑制剂的敏感性的影响。我们发现突变体N156-T158 A、N197-S199 A、N262-S264 A和N410-T412 A赋予降低的感染性和增强的对一系列抗体和进入抑制剂的敏感性。当用野生型或突变的gp 160、gp 140或gp 120的DNA免疫小鼠时：N156-T158 A、N262-S264 A和N410-T412 A在诱导针对野生型MWS 2以及异源IIIB和CH 811 Env的中和活性方面更有效。一般来说，与gp 120相比，gp 160和gp 140诱导更高的中和活性。我们的研究首次证明了单个聚糖N156的去除。靠近CD 4结合区的N262或N410削弱病毒感染性，并导致诱导中和活性的能力增强。(C)2011 Elsevier Inc. All rights reserved.
Glycosylation plays important roles in gp120 structure and HIV-1 immune evasion. In the current study, we introduced deglycosylations into the 24 N-linked glycosylation sites of a R5 env MWS2 cloned from semen and systematically analyzed the impact on infectivity, antigenicity, immunogenicity and sensitivity to entry inhibitors. We found that mutants N156-T158A, N197-S199A, N262-S264A and N410-T412A conferred decreased infectivity and enhanced sensitivity to a series of antibodies and entry inhibitors. When mice were immunized with the DNA of wild-type or mutated gp160, gp140 or gp120: N156-T158A, N262-S264A and N410-T412A were more effective in inducing neutralizing activity against wild-type MWS2 as well as heterologous IIIB and CH811 Envs. In general, gp160 and gp140 induced higher neutralizing activity compared with gp120. Our study demonstrates for the first time that removal of individual glycan N156. N262 or N410 proximal to CD4-binding region impairs viral infectivity and results in enhanced capability to induce neutralizing activity. (C) 2011 Elsevier Inc. All rights reserved.