ArticlePLoS biology2024
Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance.
Article in PLoS biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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63 citing papers in PubMed.
- HA thermostability mutations S84F, G167N, and D168N potentiate H9N2 virus transmission in a warming environment.Emerging microbes & infections · 2026Article
- Receptor-binding specificity and antigenic properties of a genotype D1.1 A(H5N1) influenza virus isolated from a human.Emerging microbes & infections · 2026Article
- Diminished sialoside binding in novel H5N1 influenza hemagglutinin variants identified in a human patient.Nature communications · 2026Article
- In silico analysis of pH stabilising mutations of hemagglutinin of influenza A virus H5N1 clade 2.3.4.4b.Npj viruses · 2026Review
- Acquisition of specific human respiratory tract binding by 2.3.4.4b H5N1 hemagglutinins requires multiple mutations.Journal of virology · 2026Article
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- Alignment-free prediction of cross-reactivity in influenza A (H3N2) anticipates antigenic drift.PLoS computational biology · 2026Article
- Concepts of RNA virus evolution for the design of better antiviral countermeasures.Nature reviews. Microbiology · 2026Review
- Defining the molecular interaction between influenza hemagglutinin and MHC-II.bioRxiv : the preprint server for biology · 2026Article
- Evolutionary constraints limit additional mammalian adaptation of bovine-derived H5N1 influenza viruses in ferrets.bioRxiv : the preprint server for biology · 2026Article
- Standing HA phenotypic breadth shapes H5N1 cross-host potential.Research square · 2026Article
- Scanning the horizon: deep mutational scanning approaches in virology.Journal of virology · 2026Review
- New determinant of influenza hemagglutinin cleavability identified through random mutagenesis for acid-stabilizing mutations.Microbiology spectrum · 2026Article
- Hemagglutinin E190D substitution in clade 2.3.4.4b A(H5N1) influenza virus reduces receptor binding and viral fitness.Npj viruses · 2026Article
- Preclinical evaluation of an mRNA vaccine developed from the first human isolate of bovine H5N1.Cell reports. Medicine · 2026Article
- The emergence and molecular evolution of H5N1 influenza viruses in United States dairy cattle.bioRxiv : the preprint server for biology · 2026Article
- Influenza hemagglutinin subtypes have different sequence constraints despite sharing extremely similar structures.bioRxiv : the preprint server for biology · 2026Article
- Stabilization of the H5 clade 2.3.4.4b hemagglutinin improves vaccine-elicited neutralizing antibody responses in mice.Science translational medicine · 2026Article
- Pathogenesis of H5N1 Clade 2.3.4.4b in dry Jersey cows following intramammary inoculation shows within-host compartmentalization.bioRxiv : the preprint server for biology · 2026Article
3 more citing papers are in PubMed but not listed here.
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Abstract
H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple nonhuman mammalian species. Previous studies have identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute to pandemic potential in humans, including cell entry, receptor preference, HA stability, and reduced neutralization by polyclonal sera. However, prior experimental work has only measured how these phenotypes are affected by a handful of the >10,000 different possible amino-acid mutations to HA. Here, we use pseudovirus deep mutational scanning to measure how all mutations to a 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind α2-6-linked sialic acids and show that some viruses already carry mutations that stabilize HA. We also measure how all HA mutations affect neutralization by sera from mice and ferrets vaccinated against or infected with 2.3.4.4b H5 viruses. These antigenic maps enable rapid assessment of when new viral strains have acquired mutations that may create mismatches with candidate vaccine virus, and we show that a mutation present in some recent H5 HAs causes a large antigenic change. Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.
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