ArticleViruses2016
Accurate Measurement of the Effects of All Amino-Acid Mutations on Influenza Hemagglutinin.
Article in Viruses, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
152 citing papers in PubMed.
- Immunogenicity of chimeric haemagglutinin-based, universal influenza virus vaccine candidates: interim results of a randomised, placebo-controlled, phase 1 clinical trial.The Lancet. Infectious diseases · 2020Trial
- HA thermostability mutations S84F, G167N, and D168N potentiate H9N2 virus transmission in a warming environment.Emerging microbes & infections · 2026Article
- An In Vitro Screen Identifies H1 Influenza Hemagglutinin Substitutions That Alter mRNA-LNP Vaccine Responses Against the Stalk Domain.Vaccines · 2026Article
- Strain-specific epistasis shapes fitness landscapes of APOBEC3G antagonism by HIV-1 Vif proteins.Science advances · 2026Article
- Scanning the horizon: deep mutational scanning approaches in virology.Journal of virology · 2026Review
- Pre-pandemic contraction, phase-specific rate variation, and site-specific antigenic adaptation shape influenza A(H3N2) evolutionary dynamics in Hubei, China.Journal of virology · 2026Article
- Overestimating zero-shot fitness prediction: Broad benchmarks mask local failures and practical limitations.bioRxiv : the preprint server for biology · 2026Article
- SynFit: Synergistic Contrastive Learning for Multi-Objective Protein Fitness Prediction and Optimization.bioRxiv : the preprint server for biology · 2026Article
- Deep Prior Framework: integrating functional specificity with general plausibility for targeted protein evolution.Briefings in bioinformatics · 2026Article
- Multi-View Transformers for Structure-Aware HA-NA Drift Risk Scoring and Mutation Hotspot Mapping.Viruses · 2026Article
- Pleiotropic mutational effects on function and stability constrain the antigenic evolution of influenza haemagglutinin.Nature ecology & evolution · 2026Article
- Learning a viral protein's vocabulary.Nature ecology & evolution · 2026Article
- Evolutionary patterns of pH1N1 and H3N2 in relation to vaccine use.BMC genomics · 2026Article
- Dominant-negative TP53 mutations potentiated by the HSF1-regulated proteostasis network.Molecular cell · 2026Article
- EZ-DMS - A Simple and Accessible Protocol and Software Package for Deep Mutational Scanning of Virus Proteins.bioRxiv : the preprint server for biology · 2026Article
- Coevolutionary constraints of Zika virus nonstructural protein 5 replication and interferon antagonism activities.bioRxiv : the preprint server for biology · 2025Article
- Fitness Landscapes of APOBEC3G Antagonism by HIV-1 Vif proteins.bioRxiv : the preprint server for biology · 2025Article
- Deep Mutational Scanning in Immunology: Techniques and Applications.Pathogens (Basel, Switzerland) · 2025Review
- Combined crystallographic fragment screening and deep mutational scanning enable discovery of Zika virus NS2B-NS3 protease inhibitors.Nature communications · 2025Article
- Variant scoring tools for deep mutational scanning.Molecular systems biology · 2025Review
92 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin-including the stalk epitopes targeted by broadly neutralizing antibodies-have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.
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