Mutational fitness landscapes of diverse human influenza H1N1 neuraminidases
- 1University of Illinois Urbana-Champaign
Abstract
While neuraminidase (NA) is emerging as a promising influenza vaccine target, it evolves rapidly and undergoes antigenic drift. However, our understanding of its evolutionary constraints remains limited. Here, we systematically quantified the replication fitness effects of >6,000 mutations for each of three antigenically diverse H1N1 NAs using deep mutational scanning. Moderate correlations among H1N1 NA fitness landscapes revealed mutations with strain-dependent replication fitness effects. Additionally, cross-subtype comparison between N1 and N2 NAs uncovered similar epistatic effects that were enriched in the C-terminal interprotomer interface. We also showed that NA mutational fitness strongly correlated between in vivo and in vitro. Characterization of 40 individually constructed NA mutants further demonstrated that NA mutational fitness depended more on its surface protein expression than on its total protein expression or endoplasmic reticulum stress induction. Overall, the large dataset generated in this work provides critical insights into the evolutionary constraints of NA.
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BibTeX
@misc{teo2026mutational,
title = {{Mutational fitness landscapes of diverse human influenza H1N1 neuraminidases}},
author = {Q. W. Teo and Z. Mou and W. Liu and H. Lv and K. J. Mao and J. J. Huang and Y. W. Huan and R. Lei and A. B. Gopal and A. Mehta and E. X. Ma and X. Dai and N. C. Wu},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.07.757144},
url = {https://www.biorxiv.org/content/10.64898/2026.10.07.757144v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Mutational fitness landscapes of diverse human influenza H1N1 neuraminidases
AU - Q. W. Teo
AU - Z. Mou
AU - W. Liu
AU - H. Lv
AU - K. J. Mao
AU - J. J. Huang
AU - Y. W. Huan
AU - R. Lei
AU - A. B. Gopal
AU - A. Mehta
AU - E. X. Ma
AU - X. Dai
AU - N. C. Wu
PY - 2026
DA - 2026/10/07
PB - bioRxiv
DO - 10.64898/2026.10.07.757144
UR - https://www.biorxiv.org/content/10.64898/2026.10.07.757144v1
AB - While neuraminidase (NA) is emerging as a promising influenza vaccine target, it evolves rapidly and undergoes antigenic drift. However, our understanding of its evolutionary constraints remains limited. Here, we systematically quantified the replication fitness effects of >6,000 mutations for each of three antigenically diverse H1N1 NAs using deep mutational scanning. Moderate correlations among H1N1 NA fitness landscapes revealed mutations with strain-dependent replication fitness effects. Additionally, cross-subtype comparison between N1 and N2 NAs uncovered similar epistatic effects that were enriched in the C-terminal interprotomer interface. We also showed that NA mutational fitness strongly correlated between in vivo and in vitro. Characterization of 40 individually constructed NA mutants further demonstrated that NA mutational fitness depended more on its surface protein expression than on its total protein expression or endoplasmic reticulum stress induction. Overall, the large dataset generated in this work provides critical insights into the evolutionary constraints of NA.
ER -