Wu Nicholas C, Wilson Ian A
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
J Mol Biol. 2017 Aug 18;429(17):2694-2709. doi: 10.1016/j.jmb.2017.06.015. Epub 2017 Jun 23.
Influenza virus evolves rapidly to constantly escape from natural immunity. Most humoral immune responses to influenza virus target the hemagglutinin (HA) glycoprotein, which is the major antigen on the surface of the virus. The HA is composed of a globular head domain for receptor binding and a stem domain for membrane fusion. The major antigenic sites of HA are located in the globular head subdomain, which is highly tolerant of amino acid substitutions and continual addition of glycosylation sites. Nonetheless, the evolution of the receptor-binding site and the stem region on HA is severely constrained by their functional roles in engaging the host receptor and in mediating membrane fusion, respectively. Here, we review how broadly neutralizing antibodies (bnAbs) exploit these evolutionary constraints to protect against diverse influenza strains. We also discuss the emerging role of other epitopes that are conserved only in subsets of viruses. This rapidly increasing knowledge of the evolutionary biology, immunology, structural biology, and virology of influenza virus is invaluable for development and design of more universal influenza vaccines and novel therapeutics.
流感病毒迅速进化，不断逃避天然免疫。大多数针对流感病毒的体液免疫反应靶向血凝素（HA）糖蛋白，它是病毒表面的主要抗原。HA由用于受体结合的球状头部结构域和用于膜融合的茎部结构域组成。HA的主要抗原位点位于球状头部亚结构域，该区域对氨基酸替换和糖基化位点的持续添加具有高度耐受性。尽管如此，HA上受体结合位点和茎区的进化分别受到它们在结合宿主受体和介导膜融合中的功能作用的严重限制。在这里，我们综述了广谱中和抗体（bnAbs）如何利用这些进化限制来抵御多种流感毒株。我们还讨论了仅在病毒亚群中保守的其他表位的新作用。对流感病毒进化生物学、免疫学、结构生物学和病毒学的这种迅速增加的了解，对于开发和设计更通用的流感疫苗及新型疗法非常宝贵。
