Analysis of antigenic variation and adaptive evolution of H5N1 neuraminidase gene 9304

Abstract Description The present concern on the H5N1 outbreak, including the rapid mutation of its core genes, underscores the threat of influenza to global health. Neuraminidase (NA), a key surface glycoprotein that plays a crucial role in the virus replication has nine subtypes, each with unique evolutionary adaptations. Despite this, there is paucity of information on the functional diversity of the 9 NA subtypes. Therefore, we set out to elucidate the functional diversity of NA subtypes, regarding its role in host adaptation. We performed a comprehensive analysis of the 9 subtypes, involving structural superimposition and structure-guided sequence alignment which enables determination of subtype-specific positions. Our results show 40 highly significant amino acid positions, possibly contributing to functional diversity among the subtypes. Furthermore, our analysis categorizes the 9 NAs into four distinct subgroups, which are: NA2, NA4 and NA1, NA9, NA7, NA6, and NA3, and finally NA8 and NA5. To investigate the role of neuraminidase subtype NA1 in host adaptation, we examined its evolutionary dynamics and relationships in H5N1 isolates from various host species, including humans, chickens, geese, turkeys, cattle, and swans. Our findings indicate that chicken NA exhibits signs of positive selection, suggesting adaptation to this host. In contrast, NA from other hosts shows evidence of purifying selection, primarily maintaining essential functions rather than driving adaptive evolution. Topic Categories Viral Immunology (VIR)