Reassortment Dynamics: Phylogeography and Evolution of H4N9 Influenza Viruses

A characteristic feature of influenza A viruses is their high capacity for reassortment, significantly increasing their genetic diversity. This can lead to the formation of influenza A virus variants with unique phenotypic characteristics, particularly those with pandemic potential. Representatives of the H4N9 subtype are low-pathogenic influenza A (LPAI) viruses. Despite their low pandemic potential, these viruses may represent an important reservoir of genes for genetic exchange with other IAVs. Here, we analyzed the reassortment events of H4N9 viruses using all publicly available sequences. Several computational approaches, including phylogenetic reconstructions and reassortment detection algorithms (PDDM and PDCP), were used to identify phylogenetic incongruences. Numerous reassortment events were detected in H4N9 viruses, especially in the NS segment. This suggests extensive genetic exchange with other avian and mammalian IAVs. In addition, a comparison of phylogenetic and geographic patterns suggests that H4N9 viruses have undergone multiple trans-regional transmissions. These results suggest that LPAI viruses make a significant contribution to the overall influenza gene pool, increasing the likelihood of the emergence of new IAV variants with unpredictable phenotypic characteristics. However, our results suggest that the current understanding of the real distribution and genetic diversity is fragmented. Therefore, better monitoring and surveillance of H4N9 viruses should improve influenza pandemic preparedness.