Mechanisms Of Humoral Evasion

HIV-1包膜包含多个重叠（和冗余）的体液免疫防御机制。这些包括聚糖屏蔽、构象掩蔽和具有可变环的免疫优势诱饵。尽管我们对其中的许多机制进行了广泛的探索，但我们仍然只了解了其中的一部分。我们使用基于结构的方法来进一步定义它们。特别是，我们已经研究了CD4结合位点如何使用构象掩蔽来隐藏大多数CD4结合位点导向抗体的CD4结合的保守位点。然而，CD4结合位点的一部分似乎仍然暴露，以满足病毒对快速CD4 on-rate的意外需求。我们最初推测该暴露位点仅与gp120 α -5螺旋和外结构域上的b12结合位点相关。然而，最近对CD4结合位点的关键部分，即界面ph -43腔的分析表明，该部位的一部分也可能参与了初始附着。

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.