Poignard P, Saphire E O, Parren P W, Burton D R
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Annu Rev Immunol. 2001;19:253-74. doi: 10.1146/annurev.immunol.19.1.253.
HIV-1 particles are decorated with a network of densely arranged envelope spikes on their surface. Each spike is formed of a trimer of heterodimers of the gp120 surface and the gp41 transmembrane glycoproteins. These molecules mediate HIV-1 entry into target cells, initiating the HIV-1 replication cycle. They are a target for entry-blocking drugs and for neutralizing Abs that could contribute to vaccine protection. The crystal structure of the core of gp120 has been recently solved. It reveals the structure of the conserved HIV-1 receptor binding sites and some of the mechanisms evolved by HIV-1 to escape Ab responses. The gp120 consists of three faces. One is largely inaccessible on the native trimer, and two faces are exposed but apparently have low immunogenicity, particularly on primary viruses. We have modeled HIV-1 neutralization by a CD4 binding site monoclonal Ab, and we propose that neutralization takes place by inhibition of the interaction between gp120 and the target cell membrane receptors as a result of steric hindrance. Knowledge of gp120 structure and function should assist in the design of new drugs as well as of an effective vaccine. In the latter case, circumventing the low immunogenicity of the HIV-1 envelope spike is a major challenge.
HIV-1病毒颗粒表面装饰有密集排列的包膜刺突网络。每个刺突由表面糖蛋白gp120和跨膜糖蛋白gp41的异二聚体三聚体形成。这些分子介导HIV-1进入靶细胞，启动HIV-1复制周期。它们是进入阻断药物和可有助于疫苗保护的中和抗体的作用靶点。gp120核心的晶体结构最近已得到解析。它揭示了保守的HIV-1受体结合位点的结构以及HIV-1为逃避抗体应答而进化出的一些机制。gp120由三个面组成。一个面在天然三聚体上基本无法接近，另外两个面是暴露的，但显然免疫原性较低，尤其是在原始病毒上。我们对一种CD4结合位点单克隆抗体介导的HIV-1中和作用进行了建模，我们提出中和作用是由于空间位阻抑制了gp120与靶细胞膜受体之间的相互作用而发生的。了解gp120的结构和功能应有助于新药以及有效疫苗的设计。在后一种情况下，规避HIV-1包膜刺突的低免疫原性是一项重大挑战。
