ArticleProceedings of the National Academy of Sciences of the United States of America2018
Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers.
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164 citing papers in PubMed, 225 citations in OpenAlex.
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- New determinant of influenza hemagglutinin cleavability identified through random mutagenesis for acid-stabilizing mutations.Microbiology spectrum · 2026Article
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- Strain-specific differences in the response to egg-derived versus recombinant protein influenza vaccines.bioRxiv : the preprint server for biology · 2026Article
- Antiviral activity and chemical characterization of Egyptian Ziziphus spina-christi against human respiratory viruses.Scientific reports · 2026Article
- Predicting the antigenic evolution of seasonal influenza viruses using phylogenetic convergence.bioRxiv : the preprint server for biology · 2026Article
- Multi-View Transformers for Structure-Aware HA-NA Drift Risk Scoring and Mutation Hotspot Mapping.Viruses · 2026Article
- Influenza hemagglutinin subtypes have different sequence constraints despite sharing extremely similar structures.bioRxiv : the preprint server for biology · 2026Article
- DEX: a consensus-based amino acid exchangeability measure for improved codon substitution modelling.bioRxiv : the preprint server for biology · 2026Article
- Characterizing Physicochemical Selection in Protein Evolution with Property-Informed Models (PRIME).bioRxiv : the preprint server for biology · 2026Article
- Comparative analysis of deep mutational scanning datasets in enteroviruses A and B identifies functional divergence and therapeutic targets.Nature ecology & evolution · 2026Article
104 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Human influenza virus rapidly accumulates mutations in its major surface protein hemagglutinin (HA). The evolutionary success of influenza virus lineages depends on how these mutations affect HA's functionality and antigenicity. Here we experimentally measure the effects on viral growth in cell culture of all single amino acid mutations to the HA from a recent human H3N2 influenza virus strain. We show that mutations that are measured to be more favorable for viral growth are enriched in evolutionarily successful H3N2 viral lineages relative to mutations that are measured to be less favorable for viral growth. Therefore, despite the well-known caveats about cell-culture measurements of viral fitness, such measurements can still be informative for understanding evolution in nature. We also compare our measurements for H3 HA to similar data previously generated for a distantly related H1 HA and find substantial differences in which amino acids are preferred at many sites. For instance, the H3 HA has less disparity in mutational tolerance between the head and stalk domains than the H1 HA. Overall, our work suggests that experimental measurements of mutational effects can be leveraged to help understand the evolutionary fates of viral lineages in nature-but only when the measurements are made on a viral strain similar to the ones being studied in nature.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.