Jenny J. Ahn, etc.,al. [preprint]Influenza hemagglutinin subtypes have different sequence constraints despite sharing extremely similar structures. https://doi.org/10.64898/2026.01.05.697808
Hemagglutinins (HA) from different influenza A virus subtypes share as little as ~40% amino acid identity, yet their protein structure and cell entry function are highly conserved. Here we examine the extent that sequence constraints on HA differ across three subtypes. To do this, we first use pseudovirus deep mutational scanning to measure how all amino-acid mutations to an H7 HA affect its cell entry function. We then compare these new measurements to previously described measurements of how all mutations to H3 and H5 HAs affect cell entry function. We find that ~50% of HA sites display substantially diverged preferences for different amino acids across the HA subtypes. The sites with the most divergent amino-acid preferences tend to be buried and have biochemically distinct wildtype amino acids in the different HA subtypes. We provide an example of how rewiring the interactions among contacting residues has dramatically shifted which amino acids are tolerated at specific sites. Overall, our results show how proteins with the same structure and function can become subject to very different site-specific evolutionary constraints as their sequences diverge.
See Also:
Latest articles in those days:
- [preprint]The mammalian-adaptive PB2-E627K substitution preserves viral fitness of clade 2.3.4.4b H5N1 HPAIV in birds 6 hours ago
- Mallard super-shedders of avian influenza exhibit distinct cloacal microbial abundance profiles 10 hours ago
- A digitally immune-optimized influenza vaccine broadly neutralizes swine and human H1N1 influenza viruses and protects from heterologous challenge 10 hours ago
- Associations between vaccine misinformation and influenza vaccine uptake: a population-based interrupted time-series study in China 10 hours ago
- Infection and transmission dynamics of bovine and human influenza A H5N1 viruses in mouse and hamster models 11 hours ago
[Go Top] [Close Window]


