Neher Richard A, Bedford Trevor, Daniels Rodney S, Russell Colin A, Shraiman Boris I
Evolutionary Dynamics and Biophysics, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany;
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;
Proc Natl Acad Sci U S A. 2016 Mar 22;113(12):E1701-9. doi: 10.1073/pnas.1525578113. Epub 2016 Mar 7.
Human seasonal influenza viruses evolve rapidly, enabling the virus population to evade immunity and reinfect previously infected individuals. Antigenic properties are largely determined by the surface glycoprotein hemagglutinin (HA), and amino acid substitutions at exposed epitope sites in HA mediate loss of recognition by antibodies. Here, we show that antigenic differences measured through serological assay data are well described by a sum of antigenic changes along the path connecting viruses in a phylogenetic tree. This mapping onto the tree allows prediction of antigenicity from HA sequence data alone. The mapping can further be used to make predictions about the makeup of the future A(H3N2) seasonal influenza virus population, and we compare predictions between models with serological and sequence data. To make timely model output readily available, we developed a web browser-based application that visualizes antigenic data on a continuously updated phylogeny.
人类季节性流感病毒进化迅速,使病毒群体能够逃避免疫力并再次感染先前感染过的个体。抗原特性很大程度上由表面糖蛋白血凝素(HA)决定,HA中暴露表位位点的氨基酸替换介导抗体识别丧失。在这里,我们表明,通过血清学检测数据测量的抗原差异可以通过系统发育树中连接病毒的路径上的抗原变化总和得到很好的描述。这种在树上的映射允许仅从HA序列数据预测抗原性。该映射还可用于预测未来A(H3N2)季节性流感病毒群体的组成,并且我们比较了使用血清学和序列数据的模型之间的预测。为了及时提供易于获取的模型输出,我们开发了一个基于网络浏览器的应用程序,该应用程序在不断更新的系统发育树上可视化抗原数据。