基于大规模基因组数据的甲型流感病毒重配模式研究

甲型流感病毒一直以来都是严重威胁人类健康的重要病原体。重配是流感病毒跳跃式进化的重要动力，历史上多次流感疫情都是由于病毒重配导致的。然而，目前关于流感病毒重配的研究主要关注某次特定疫情或某种特定亚型病毒的重配过程，缺少对流感病毒重配的系统性、规律性认识，尤其对重配模式和限制性因素的挖掘还不够完整和深入。随着测序技术的不断进步，目前已经积累了大量的流感病毒全基因组序列，本课题拟基于大规模基因组测序数据，建立面向分节段 RNA 病毒的自动化重配检测方法，系统构建流感病毒重配历史，还原流感进化历程中的重配事件，分析重配事件的频率特征。通过建立以流感病毒基因组为整体的适应性量化模型，比较病毒重配前后的适应性差异，结合病毒节段间的协同进化模式，研究病毒重配可能的促成因素和限制性因素，探索实现对特定地域可能发生的流感病毒重配事件进行风险评估，为我国甲型流感病毒防控做一点基础性研究工作。

Influenza A viruses have long been an important pathogen that poses a serious threat to human health. Reassortment is an important driving force for the evolution of influenza viruses. Many influenza epidemics were caused by virus reassortment. However, the current research on the reassortment of influenza virus is mainly concerned with the re-matching process of a specific epidemic or a special subtype of virus, lacking of comprehensive understanding of influenza virus reassortment history, especially for the reassortment mode and restrictive factors. With the continuous advancement of sequencing technology, a large number of genome sequences of influenza virus have been accumulated. Based on large-scale genome sequencing data, this project aims to establish an automated reassortment detection method for segmented RNA viruses to systematically construct influenza virus reassortment history. We will restore all the possible reassortment events in the evolution of influenza, and analyze the frequency characteristics. By establishing a quantitative fitness model of influenza A virus based on the genomes, we can compare the fitness differences before and after virus reassortment. Combined with the co-evolution mode of the segments in the viruses, the motivating factors and limiting factors of virus reassortment will be thoroughly studied. Based on the result of the project, we may provide risk assessment of influenza virus reassortment events that may occur in a specific region. Hopefully, we can do some basic research work for the prevention and control of influenza A virus in China.