ArticleCell host & microbe2022
The evolutionary potential of influenza A virus hemagglutinin is highly constrained by epistatic interactions with neuraminidase.
Article in Cell host & microbe, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Article
- In silico analysis of pH stabilising mutations of hemagglutinin of influenza A virus H5N1 clade 2.3.4.4b.Npj viruses · 2026Review
- From sites to structure to serology: a roadmap for structure-aware molecular evolution of antigenically evolving viruses.Journal of virology · 2026Review
- Scanning the horizon: deep mutational scanning approaches in virology.Journal of virology · 2026Review
- Quantum Dot-Based Dual-Fluorescence Aptasensing Platform Using Interface-Engineered MXene for Multiplex Protein Detection.Sensors (Basel, Switzerland) · 2026Article
- Deceleration and rebound of hemagglutinin divergence in influenza B/Victoria across COVID-19 NPI phases (2016-2024).Frontiers in microbiology · 2026Article
- Stochastic intracellular replication dynamics shape population-level evolution in Influenza A Virus.Virus evolution · 2026Article
- TfR1 facilitates influenza virus endocytosis and uncoating by interacting with NA and M1 via extracellular and intracellular domains.PLoS pathogens · 2025Article
- Antigenic drift expands influenza viral escape pathways from recalled humoral immunity.Immunity · 2025Article
- The importance of epistasis in the evolution of viral pathogens.Virus evolution · 2025Review
- Measures of Population Immunity Can Predict the Dominant Clade of Influenza A (H3N2) in the 2017-2018 Season and Reveal Age-Associated Differences in Susceptibility and Antibody-Binding Specificity.Influenza and other respiratory viruses · 2024Article
- Measures of population immunity can predict the dominant clade of influenza A (H3N2) in the 2017-2018 season and reveal age-associated differences in susceptibility and antibody-binding specificity.medRxiv : the preprint server for health sciences · 2024Article
- Evolutionary Insights from Association Rule Mining of Co-Occurring Mutations in Influenza Hemagglutinin and Neuraminidase.Viruses · 2024Article
- Real-time identification of epistatic interactions in SARS-CoV-2 from large genome collections.Genome biology · 2024Article
- Article
- Molecular characterization of the whole genome of H9N2 avian influenza virus isolated from Egyptian poultry farms.Archives of virology · 2024Article
- Natural variation in neuraminidase activity influences the evolutionary potential of the seasonal H1N1 lineage hemagglutinin.Virus evolution · 2024Article
- Co-evolution of immunity and seasonal influenza viruses.Nature reviews. Microbiology · 2023Review
- Global Prevalence and Hemagglutinin Evolution of H7N9 Avian Influenza Viruses from 2013 to 2022.Viruses · 2023Article
- Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3.Nature communications · 2023Article
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5 authors.
Funding
Abstract
Antigenic evolution of the influenza A virus (IAV) hemagglutinin (HA) gene limits efforts to effectively control the spread of the virus in the population. Efforts to understand the mechanisms governing HA antigenic evolution typically examine the HA gene in isolation. This can ignore the importance of balancing HA receptor binding activities with the receptor-destroying activities of the viral neuraminidase (NA) to maintain viral fitness. We hypothesize that the need to maintain functional balance with NA significantly constrains the evolutionary potential of the HA. We use deep mutational scanning and show that variation in NA activity significantly reshapes the HA fitness landscape by modulating the overall mutational robustness of HA. Consistent with this, we observe that different NA backgrounds support the emergence of distinct repertoires of HA escape variants under neutralizing antibody pressure. Our results reveal a critical role for intersegment epistasis in influencing the evolutionary potential of the HA gene.
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