Mechanisms Of Humoral Evasion

体液逃避的机制

• 批准号: 7732746
• 负责人: Peter D Kwong
• 金额: $ 30.87万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7732746
• 关键词: Antibodies; Binding; Binding Sites; Goals; HIV Envelope Protein gp120; HIV-1; HIV-1 vaccine; Helix (Snails); Immune; Immune response; Infection; Masks; Methods; Polysaccharides; Rate; Site; Structure; Viral; Virus; base; design; ear helix; interfacial; response

The HIV-1 envelope contains multiply overlapping (and redundant) mechanisms of humoral immune defence. These including glycan shielding, conformational masking, and immunodominant decoys with variable loops. Although explored extensively, many of these mechanisms are still only partially understood. We are using structure-based methods to define them further. In particular, we have investigated how the CD4-binding-site uses conformational masking to hide the conserved site of CD4 binding from most CD4-binding-site-directed antibodies. A portion of the CD4-binding site, however, appears to remain exposed to fulfill an unexpected viral requirement for a rapid CD4 on-rate. We initially presumed that this exposed site related solely to the site of b12 binding, on the alpha-5 helix and outer domain of gp120. However, recent analysis of the a critical part of the CD4 binding site, the interfacial Phe-43 cavity, suggests that part of this site may also be involved in initial attachment.

HIV-1包膜包含体液免疫防御的多重重叠（和冗余）机制。 这些包括聚糖屏蔽，构象遮罩和具有可变环的免疫主导诱饵。 尽管经过广泛的探索，但其中许多机制仍然仅部分理解。 我们正在使用基于结构的方法来进一步定义它们。 特别是，我们研究了CD4结合位点如何使用构象掩模来隐藏大多数CD4结合位置定向抗体的CD4结合位点。 然而，CD4结合位点的一部分似乎仍然暴露于快速CD4速率的意外病毒需求。 我们最初认为，这种暴露的位点仅与gp120的alpha-5螺旋和外部结构域上的B12结合位点有关。 但是，最近对CD4结合位点的关键部分的界面PHE-43腔的分析表明，该位点的一部分也可能参与初始附着。