HIV-1 gp120 Determinants Proximal to the CD4 Binding Site Shift Protective Glycans That Are Targeted by Monoclonal Antibody 2G12
HIV-1 gp120 Determinants Proximal to the CD4 Binding Site Shift Protective Glycans That Are Targeted by Monoclonal Antibody 2G12
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DOI：
10.1128/jvi.00185-10
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发表时间：
2010-09-15
影响因子：
5.4
通讯作者：
Clapham, Paul R.
中科院分区：
文献类型：
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作者：
Duenas-Decamp, Maria J.;Clapham, Paul R.
HIV-1 R5 包膜在利用巨噬细胞上低 CD4 水平进行感染的能力以及对 CD4 结合位点 (CD4bs) 单克隆抗体 (MAb) b12 和聚糖特异性 MAb 2G12 的敏感性方面存在很大差异。在这里，我们发现 CD4 结合环侧翼的非聚糖决定簇影响 CD4b 的暴露，也调节 2G12 中和。我们的数据表明，此类残基通过涉及近端聚糖方向变化的机制发挥作用，从而调节 2G12 中和的敏感性并影响聚糖屏蔽的整体呈现和结构。
HIV-1 R5 envelopes vary considerably in their capacities to exploit low CD4 levels on macrophages for infection and in their sensitivities to the CD4 binding site (CD4bs) monoclonal antibody (MAb) b12 and the glycan-specific MAb 2G12. Here, we show that nonglycan determinants flanking the CD4 binding loop, which affect exposure of the CD4bs, also modulate 2G12 neutralization. Our data indicate that such residues act via a mechanism that involves shifts in the orientation of proximal glycans, thus modulating the sensitivity of 2G12 neutralization and affecting the overall presentation and structure of the glycan shield.