Yokoyama Masaru
Laboratory of Viral Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi Murayama-shi, Tokyo 208-0011, Japan.
Uirusu. 2011 Jun;61(1):49-57. doi: 10.2222/jsv.61.49.
The third variable region (V3) of the human immunodeficiency virus type 1 (HIV-1) envelope gp120 subunit participates in determination of viral infection co-receptor tropism and host humoral immune responses. Positive charge of the V3 plays a key role in determining viral co-receptor tropism. In our previous papers, we showed a key role of the V3's net positive charge in the immunological escape and co-receptor tropism evolution in vivo. On the other hand, the several papers suggested that trimeric gp120s are protected from immune system by occlusion on the oligomer, by mutational variation, by carbohydrate masking and by conformational masking. If we can reveal the mechanism of neutralization escape, we expect that we will regulate the neutralization of HIV-1. In this review, we will overview the structural mechanism of neutralization escape of HIV-1 gp120 examined by computational science. The computational sciences for virology can provide more valuable information in combination with genomic and experimental science.
人类免疫缺陷病毒1型(HIV-1)包膜糖蛋白120亚基的第三个可变区(V3)参与病毒感染共受体嗜性的确定和宿主体液免疫反应。V3的正电荷在决定病毒共受体嗜性方面起关键作用。在我们之前的论文中,我们展示了V3的净正电荷在体内免疫逃逸和共受体嗜性进化中的关键作用。另一方面,几篇论文表明,三聚体gp120通过在寡聚体上的封闭、突变变异、碳水化合物掩盖和构象掩盖而免受免疫系统攻击。如果我们能够揭示中和逃逸的机制,我们期望能够调控HIV-1的中和作用。在这篇综述中,我们将概述通过计算科学研究的HIV-1 gp120中和逃逸的结构机制。病毒学的计算科学与基因组学和实验科学相结合可以提供更有价值的信息。