基于HA和NA基因的共进化网络研究H7N9病毒的致病性

Evolution of HA and NA genes plays an important role in the pathogenicity of H7N9 avian influenza virus. Previous studies on the co-evolution of HA and NA genes focused mainly on the relationship between single-site variations and pathogenicity. However, there is a lack of systematic studies on the impact of co-evolution of HA and NA genes on the pathogenicity of H7N9 avian influenza virus. In this study, we constructed a co-evolution network of H7N9 influenza virus HA and NA genes based on their variations. The network can be divided into two clusters based on connectivity, and low connectivity viruses are all highly pathogenic H7N9 avian influenza viruses. The nucleotide sites corresponding to the unique edges of these viruses have strong specificity. Furthermore, we analyzed the differences in eight co-evolutionary sites corresponding to 12 common edges of highly and low pathogenic H7N9 avian influenza viruses, and found that the dominant amino acids at these sites are significantly associated with pathogenicity, and show different amino acid compositions in different pathogenic H7N9 viruses. Finally, we compared with the reported sites in current experimental studies and identified three key sites, 130, 143, and 235 (H7 numbering), that may affect the pathogenicity of H7N9 virus. Our study deepens the understanding of the pathogenic mechanism of H7N9 avian influenza virus and provides reference for the study of the pathogenic mechanism of other subtypes of avian influenza viruses.