Mutational fitness landscape of human influenza H3N2 neuraminidase.

ABSTRACT: Influenza neuraminidase (NA) has received increasing attention as an effective vaccine target. However, its mutational tolerance is not well characterized. Here, the fitness effects of >6,000 mutations in human H3N2 NA are probed using deep mutational scanning. Our result shows that while its antigenic regions have high mutational tolerance, there are solvent-exposed regions with low mutational tolerance. We also find that protein stability is a major determinant of NA mutational fitness. The deep mutational scanning result correlates well with mutational fitness inferred from natural sequences using a protein language model, substantiating the relevance of our findings to the natural evolution of circulating strains. Additional analysis further suggests that human H3N2 NA is far from runn

SUBMITTER: Lei R 

PROVIDER: S-EPMC9931530 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature