Williams Blake J M, Ogbunugafor C Brandon, Althouse Benjamin M, Hébert-Dufresne Laurent
Vermont Complex Systems Center, University of Vermont, Burlington, VT 05405, USA.
Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USA.
PNAS Nexus. 2022 Aug 5;1(4):pgac143. doi: 10.1093/pnasnexus/pgac143. eCollection 2022 Sep.
Seasonal influenza kills hundreds of thousands every year, with multiple constantly changing strains in circulation at any given time. A high mutation rate enables the influenza virus to evade recognition by the human immune system, including immunity acquired through past infection and vaccination. Here, we capture the genetic similarity of influenza strains and their evolutionary dynamics with genotype networks. We show that the genotype networks of influenza A (H3N2) hemagglutinin are characterized by heavy-tailed distributions of module sizes and connectivity indicative of critical behavior. We argue that (i) genotype networks are driven by mutation and host immunity to explore a subspace of networks predictable in structure and (ii) genotype networks provide an underlying structure necessary to capture the rich dynamics of multistrain epidemic models. In particular, inclusion of strain-transcending immunity in epidemic models is dependent upon the structure of an underlying genotype network. This interplay is consistent with self-organized criticality where the epidemic dynamics of influenza locates critical regions of its genotype network. We conclude that this interplay between disease dynamics and network structure might be key for future network analysis of pathogen evolution and realistic multistrain epidemic models.
季节性流感每年导致数十万人死亡，在任何给定时间都有多种不断变化的毒株在传播。高突变率使流感病毒能够逃避人体免疫系统的识别，包括通过既往感染和接种疫苗获得的免疫力。在此，我们利用基因型网络捕捉流感毒株的遗传相似性及其进化动态。我们表明，甲型（H3N2）流感血凝素的基因型网络具有模块大小和连通性的重尾分布特征，这表明存在临界行为。我们认为：（i）基因型网络由突变和宿主免疫驱动，以探索结构可预测的网络子空间；（ii）基因型网络提供了捕捉多毒株流行模型丰富动态所需的基础结构。特别是，在流行模型中纳入跨毒株免疫力取决于潜在基因型网络的结构。这种相互作用与自组织临界性一致，即流感的流行动态定位其基因型网络的临界区域。我们得出结论，疾病动态与网络结构之间的这种相互作用可能是未来病原体进化网络分析和现实多毒株流行模型的关键。
