Concanavalin A binding to HIV envelope protein is less sensitive to mutations in glycosylation sites than monoclonal antibody 2G12.
Concanavalin A binding to HIV envelope protein is less sensitive to mutations in glycosylation sites than monoclonal antibody 2G12.
复制标题
与单克隆抗体 2G12 相比，伴刀豆球蛋白 A 与 HIV 包膜蛋白的结合对糖基化位点的突变不太敏感。
DOI：
10.1093/glycob/cwi083
复制
发表时间：
2005
期刊：
影响因子：
4.3
通讯作者：
Kieber-Emmons,Thomas
中科院分区：
文献类型：
--
作者：
Pashov,Anastas;MacLeod,Stewart;Saha,Rinku;Perry,Marty;VanCott,ThomasC;Kieber-Emmons,Thomas
在病毒感染性的体外模型中，许多甘露糖结合蛋白抑制人类免疫缺陷病毒1型(HIV-1)的不同毒株，这表明在疫苗应用中针对甘露糖残留物可能抵消通常在HIV疫苗制备的抗体反应中观察到的毒株限制。刀豆蛋白A(ConA)的作用类似于中和抗体，不干扰gp120的CD4结合，而是干扰病毒进入的后续事件。因此，基于甘露糖的疫苗的设计依赖于了解ConA与包膜蛋白的结合方式与其他甘露糖结合蛋白的比较。在这里，我们进一步比较ConA与包膜蛋白的结合亲和力和良好的特异性与人类抗体2G12的结合亲和力和良好的特异性。2G12抗体具有不寻常的结构，识别与Man9GlcNAc2相关的12个连接的甘露糖残基。ConA和2G12识别Man9GlcNAc2的分子结构比较表明，2G12对gp120的高甘露糖具有更有限的特异性，这与表面等离子体共振(SPR)动力学分析相关联，ConA抑制2G12与gp120的结合，而2G12不抑制ConA与gp120的结合。ConA与来自四个不同HIV毒株的Env蛋白结合证明，与2G12结合蛋白相比，ConA对糖基化位点突变的敏感性要低得多。因此，从长远来看，针对与ConA反应的甘露糖表位的抗体可能被证明更有效地阻止艾滋病毒的感染和传播。
Many mannose-binding proteins inhibit divergent strains of human immunodeficiency virus type 1 (HIV-1) in in vitro models of viral infectivity, suggesting that targeting mannose residues in vaccine applications might offset the strain restriction typically observed in antibody responses to HIV vaccine preparations. Concanavalin A (ConA) behaves like neutralizing antibodies that do not interfere with CD4 binding of gp120 but rather with later events in virus entry. The design of mannose-based vaccines, therefore, depends on understanding the mode of binding of ConA to the envelope protein in comparison with other mannose-binding proteins. Here, we further compare the binding affinity and fine specificity of ConA for the envelope protein to that of the human antibody 2G12. The 2G12 antibody is of unusual structure recognizing a cluster of 12 linked mannose residues associated with Man9GlcNAc2. Molecular structure comparison for Man9GlcNAc2 recognition by ConA and 2G12 indicates that 2G12 has a more restricted specificity to high mannose glycans of gp120 which correlates with kinetic analysis assessed by surface plasmon resonance (SPR) and ConA inhibits 2G12 binding to gp120 but 2G12 does not inhibit ConA binding to gp120. ConA binding to Env proteins from four different HIV strains proves significantly less sensitive to mutations in the glycosylation sites than 2G12 binding to the proteins. Thus, antibodies directed toward mannose epitopes reactive with ConA may prove to be more effective in the long run to thwart HIV infection and transmission.