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和聚糖屏蔽来隐藏CD4结合的保守位点，使其不受大多数CD4结合位点定向抗体的影响。我们还研究了包络结构如何提供构象迁移。这些构象层在HIV-1 gp120内结构域中调节gp41相互作用和cd4触发的构象转变。

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 and glycan shielding to hide the conserved site of CD4 binding from most CD4-binding-site-directed antibodies. We have also investigated how the envelope architecture provides for conformational mobility. These conformational layers in the HIV-1 gp120 inner domain regulate gp41 interactions and CD4-triggered conformational transitions.