Logo

Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance

Methodologically Supported Linked to Data Early Sharing / Preprint ↗
Author(s): Bernadeta Dadonaite, Jenny Ahn, Jordan T. Ort, Yu Jin, Colleen Furey, Annie Dosey, William W. Hannon, Amy L. Vincent Baker, Richard J. Webby, Neil P. King, Yan Liu, Scott E. Hensley, Thomas P. Peacock, Louise H. Moncla, Jesse D. Bloom
Publisher: PLoS Biology
Publication year: 2024

The Story So Far

Short impact summary

The study "Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance" has garnered significant attention, with 79 citations since publication. The research is grounded in prominent institutions such as St. Jude Children's Research Hospital and the University of Washington, and has also received robust financial backing from entities like the NIH and the Biotechnology and Biological Sciences Research Council.

Full narrative

The research article titled "Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance" has emerged as a pivotal contribution to the field of virology, particularly in understanding influenza virus dynamics. Since its release, the study has received considerable academic acknowledgment, evidenced by a citation count of 79, indicating its relevance to ongoing conversations in the scientific community. The work was supported by esteemed institutions like St. Jude Children's Research Hospital, the University of Washington, and Howard Hughes Medical Institute, underscoring the collaborative efforts driving this vital research.

One of the hallmarks of this research is its commitment to open science practices, exemplified by the early dissemination of findings through a preprint version. This preprint effectively primed the community for subsequent discussion and engagement, accumulating 16 citations and generating four early sharing events. Such contributions reflect a proactive approach to science, facilitating immediate discourse and collaboration prior to formal publication in a peer-reviewed venue like PLoS Biology.

Furthermore, the work is reinforced by substantial financial investment from key funding agencies, including the National Institute of Health and the Biotechnology and Biological Sciences Research Council. This financial backing not only validates the significance of the research but also reflects a broader institutional interest in enhancing influenza surveillance methodologies. The multi-faceted support reveals an extensive commitment to advancing public health through sound scientific research.

In terms of community engagement, while the study has yet to generate significant online discussion on platforms like Wikipedia or Reddit, it has inspired dialogues within the academic sphere, with a noted presence in reputable venues such as bioRxiv and npj Viruses. This indicates the study's potential to influence ongoing research and discourse surrounding influenza virus surveillance. Additionally, the use of resources like Zenodo and GitHub for data sharing exemplifies the authors' commitment to enhancing the reproducibility and accessibility of their research, allowing fellow scientists to build upon their findings effectively.

Impact metrics

Inferred roles

Heuristic classification from citation composition / usage signals. Not based on full text.

High-visibility uptake (0.85) Scholarly uptake (0.73) Sustainability & policy relevance (0.55) Rapid uptake (0.46) Active public discourse (0.42)

Access OpenAlex

Attention landscape Event Data

This work has 2 recorded events globally (combined from the published article and preprint).

(See specific sources and examples in the Online Mentions section below).

Citation context scite

  • Total: 19
  • Supporting: 1
  • Mentioning: 18
  • Contradicting: 0

Scientific Stewardship Europe PMC / DataCite

Associated data repositories and clinical trials.

Data Repositories & Code

Who is citing this work? OpenAlex

Analysis of the 79 most recent citing works.
101.6% of these citations come from the Top 10 institutions below. The median citing paper has gone on to be cited 1.0 times itself.

Global Reach (Top Countries)

United States (40) Canada (6) Netherlands (6) South Africa (6) India (5) United Kingdom (4) Hong Kong (4) China (4) Japan (3) Switzerland (2) Belgium (2) Lithuania (1)

Institutional Sectors

Education (53) Nonprofit (24) Facility (22) Healthcare (15) Government (9)

Top Citing Institutions

  • University of Washington ROR (12)
  • Fred Hutch Cancer Center ROR (12)
  • Howard Hughes Medical Institute ROR (10)
  • University of Pennsylvania ROR (5)
  • Utrecht University ROR (5)
  • Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa ROR (5)
  • Scripps Research Institute ROR (4)
  • University of Georgia ROR (4)
  • University of Hong Kong ROR (4)
  • Centers for Disease Control and Prevention ROR (3)

Most Frequent Citers

  • Citing work types: article (34) preprint (18) review (7) letter (3) editorial (1)
  • Top citing venues: bioRxiv (17) bioRxiv (Cold Spring Harbor Laboratory) (5) npj Viruses (3) Nature (2) Nature Communications (2)
  • Top citing concepts: Virology (31) Influenza A virus subtype H5N1 (26) Biology (25) Hemagglutinin (influenza) (14) Computational biology (6) Virus (4) Clade (4) Mutation (3)
  • Citation timeline:

Online mentions & activity Crossref & Open Web

Community Engagement & Discourse

Bluesky Post 2024-11-22
"Pseudovirus deep mutational scanning reveals mutations in 2.3.4.4b H5 HA affect phenotype, e.g. binding to α2-6-linked sialic acids, HA stabilisation,..." — @duckswabber.bsky.social
View Thread ↗
Displaying the 1 most detailed mentions. Other aggregated events lack public URLs.

Contributors & affiliations OpenAlex

15 authors · 7 institutions

Authors

  • Bernadeta Dadonaite First Corresponding ORCID
  • Jenny Ahn Corresponding ORCID
  • Jordan T. Ort Corresponding ORCID
  • Yu Jin Corresponding ORCID
  • Colleen Furey Corresponding ORCID
  • Annie Dosey Corresponding ORCID
  • William W. Hannon Corresponding ORCID
  • Amy L. Vincent Baker Corresponding
  • Richard J. Webby Corresponding
  • Neil P. King Corresponding ORCID
  • Yan Liu Corresponding ORCID
  • Scott E. Hensley Corresponding ORCID
  • Thomas P. Peacock Corresponding ORCID
  • Louise H. Moncla Corresponding ORCID
  • Jesse D. Bloom Corresponding ORCID

Institutions

Concepts & topics OpenAlex

13 specific concepts identified.
Biology Hemagglutinin (influenza) Virology Virus Mutation Influenza A virus Neutralization Phenotype Antigenic drift Mutagenesis Sialic acid Gene Genetics

UN Sustainable Development Goals OpenAlex

1 targets detected.
Good health and well-being (0.85)

Research Funding Europe PMC / OpenAlex

19 financial grants and sponsors detected.
Biotechnology and Biological Sciences Research Council (BBS/E/PI/230002B) NIAID NIH HHS (R01 AI141707) National Institute of Health (S10-OD-020069) NIAID NIH HHS (75N93021C00015) Howard Hughes Medical Institute Division of Intramural Research, National Institute of Allergy and Infectious Diseases (AI47029) Biotechnology and Biological Sciences Research Council (BBS/E/PI/230002A; BBS/E/PI/230002B) Division of Intramural Research, National Institute of Allergy and Infectious Diseases (R01AI141707) NIH HHS (S10 OD028685) Biotechnology and Biological Sciences Research Council (BB/Y007298/1) Medical Research Council (MR/R010757/1) NIH HHS (S10 OD020069) Open Philanthropy Project NIAID NIH HHS (R00 AI147029) NIAID NIH HHS (R01 AI165821) Division of Intramural Research, National Institute of Allergy and Infectious Diseases (R01AI165821) Division of Intramural Research, National Institute of Allergy and Infectious Diseases (75N93021C00015) Medical Research Foundation (MR/Y03368X/1) National Institute of Health (S10-OD-028685)

Citations OpenAlex

Displaying 63 most recent citing works
YearTitleVenueDOI
2024 The global H5N1 influenza panzootic in mammals Nature 10.1038/s41586-024-08054-z
2024 A single mutation in bovine influenza H5N1 hemagglutinin switches specificity to human receptors Science 10.1126/science.adt0180
2024 Critical Illness in an Adolescent with Influenza A(H5N1) Virus Infection New England Journal of Medicine 10.1056/nejmc2415890
2024 A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth Nature Communications 10.1038/s41467-024-54934-3
2025 Receptor-binding specificity of a bovine influenza A virus Nature 10.1038/s41586-025-08822-5
2025 H5N1 2.3.4.4b: a review of mammalian adaptations and risk of pandemic emergence Journal of General Virology 10.1099/jgv.0.002109
2025 Multiplexed assays of variant effect for clinical variant interpretation Nature Reviews Genetics 10.1038/s41576-025-00870-x
2025 Large-scale computational modelling of H5 influenza variants against HA1-neutralising antibodies EBioMedicine 10.1016/j.ebiom.2025.105632
2025 Strategies and efforts in circumventing the emergence of antiviral resistance against conventional antivirals npj Antimicrobials and Resistance 10.1038/s44259-025-00125-z
2025 Structure of a zoonotic H5N1 hemagglutinin reveals a receptor-binding site occupied by an auto-glycan Structure 10.1016/j.str.2025.01.001
2025 Deep mutational scanning of rabies glycoprotein defines mutational constraint and antibody-escape mutations Cell Host & Microbe 10.1016/j.chom.2025.04.018
2025 Pleiotropic mutational effects on function and stability constrain the antigenic evolution of influenza haemagglutinin Nature Ecology & Evolution 10.1038/s41559-025-02895-1
2025 Attachment and replication of clade 2.3.4.4b influenza A (H5N1) viruses in human respiratory epithelium: an in-vitro study The Lancet Microbe 10.1016/j.lanmic.2025.101230
2025 Balancing stability and function: impact of the surface charge of SARS-CoV-2 Omicron spike protein npj Viruses 10.1038/s44298-025-00104-1
2025 The sweet side of H5N1 influenza virus infection PLoS Pathogens 10.1371/journal.ppat.1012847
2025 The Q226L mutation can convert a highly pathogenic H5 2.3.4.4e virus to bind human-type receptors Proceedings of the National Academy of Sciences 10.1073/pnas.2419800122
2025 Cross-neutralizing and potent human monoclonal antibodies against historical and emerging H5Nx influenza viruses Nature Microbiology 10.1038/s41564-025-02137-x
2025 Mutations in the influenza virus, primarily H5N1, enhance the virus’s virulence, favor receptor interaction, and increase drug resistance International Journal of Surgery 10.1097/js9.0000000000002403
2025 Impact of naturally occurring hemagglutinin substitutions on antigenicity and fitness of influenza A(H5N1) virus npj Viruses 10.1038/s44298-025-00154-5
2025 Development of avian influenza A(H5) virus datasets for Nextclade enables rapid and accurate clade assignment Virus Evolution 10.1093/ve/veaf058
2026 Management of critical illness in an adolescent caused by highly pathogenic avian influenza A(H5N1) virus infection in British Columbia, Canada The Lancet Infectious Diseases 10.1016/s1473-3099(25)00773-x
2026 Pathogenesis of H5N1 Clade 2.3.4.4b in dry Jersey cows following intramammary inoculation shows within-host compartmentalization bioRxiv (Cold Spring Harbor Laboratory) 10.64898/2026.03.04.709389
2024 Analysis of the Monophyletic Lineage of Avian Influenza H5N1 Which Circulated in Venezuelan Birds During the 2022–2023 Outbreak Microorganisms 10.3390/microorganisms12122519
2025 Decoding non-human mammalian adaptive signatures of 2.3.4.4b H5N1 to assess its human adaptive potential Microbiology Spectrum 10.1128/spectrum.00948-25
2025 Nonviral protein cages as tools to decipher and combat viral threats npj Viruses 10.1038/s44298-025-00127-8
2025 Risk assessment of 2024 cattle H5N1 using age-stratified serosurveillance data Emerging Microbes & Infections 10.1080/22221751.2025.2497304
2025 A review of the animal influenza viruses and their impact on human health Discover Public Health 10.1186/s12982-025-00679-3
2024 Receptor Binding Specificity of a Bovine A(H5N1) Influenza Virus bioRxiv 10.1101/2024.07.30.605893
2025 Pleiotropic mutational effects on function and stability constrain the antigenic evolution of influenza hemagglutinin bioRxiv 10.1101/2025.05.24.655919
2025 Susceptibility of bovine respiratory and mammary epithelial cells to avian and mammalian derived clade 2.3.4.4b H5N1 highly pathogenic avian influenza viruses bioRxiv 10.1101/2025.01.09.632235
2024 Deep mutational scanning of rabies glycoprotein defines mutational constraint and antibody-escape mutations bioRxiv 10.1101/2024.12.17.628970
2025 H5N1 Influenza A is now promiscuous in host range and has improved replication in mammals bioRxiv 10.1101/2025.03.15.641219
2025 Evaluating variant effect prediction across viruses bioRxiv 10.1101/2025.08.04.668549
2025 The Q226L mutation can convert a highly pathogenic H5 2.3.4.4e virus to bind human-type receptors bioRxiv 10.1101/2025.01.10.632119
2025 Seasonal influenza viruses show distinct adaptive dynamics during growth in chicken eggs bioRxiv 10.1101/2025.06.12.659400
2024 Structure of a zoonotic H5N1 hemagglutinin reveals a receptor-binding site occupied by an auto-glycan bioRxiv 10.1101/2024.12.06.626699
2024 PLOS Biology and the life sciences in 2024 PLoS Biology 10.1371/journal.pbio.3002985
2024 Risk assessment of 2024 cattle H5N1 using age-stratified serosurveillance data bioRxiv 10.1101/2024.12.23.24319580
2024 Predictive Modeling of Respiratory Virus Evolution: Current Capabilities and Limitations Mathematical Biology and Bioinformatics 10.17537/2024.19.579
2025 A Fine-tuned ProtGPT2 (transformer model) for Predicting more Virulent SARS-CoV-2 variants and understanding its virulence by biophysical methods bioRxiv 10.1101/2025.01.13.632691
2025 Lengthy delays in H5N1 genome submissions to GISAID Nature Biotechnology 10.1038/s41587-025-02636-6
2025 Preclinical Evaluation of an mRNA Vaccine Developed from the First Human Isolate of Bovine H5N1 SSRN Electronic Journal 10.2139/ssrn.5353082
2025 Random mutagenesis of influenza hemagglutinin identifies new sites which modulate its acid-stability and cleavability bioRxiv 10.1101/2025.07.25.666873
2025 Stabilization of H5 highly pathogenic avian influenza hemagglutinin improves vaccine-elicited neutralizing antibody responses bioRxiv 10.1101/2025.07.30.667762
2025 Insights from deep mutational scanning in the context of an emerging pathogen Biochemical Society Transactions 10.1042/bst20253033
2025 Host Switching Mutations in H5N1 Influenza Hemagglutinin Suppress Site-specific Activation Dynamics bioRxiv 10.1101/2025.10.06.680362
2025 Targeted tiled amplicon based protocol for sequencing the Hemagglutinin (HA) gene segment of seasonal influenza A and influenza B virus from wastewater at high depth of coverage bioRxiv 10.1101/2025.10.15.25338105
2025 Functional and antigenic constraints on the Nipah virus fusion protein bioRxiv 10.1101/2025.10.15.682664
2025 Inverted H1 hemagglutinin nanoparticle vaccines protect mice against challenges with human H1N1 and bovine H5N1 influenza viruses npj Vaccines 10.1038/s41541-025-01276-w
2025 AbAgym: a well-curated dataset for the mutational analysis of antibody–antigen complexes mAbs 10.1080/19420862.2025.2592421
2025 Mutational spectra reveal influenza virus transmission routes and adaptation bioRxiv 10.1101/2025.11.26.690773
2025 Learning a viral protein’s vocabulary Nature Ecology & Evolution 10.1038/s41559-025-02928-9
2025 Host switching mutations in H5N1 influenza hemagglutinin suppress site-specific activation dynamics Nature Communications 10.1038/s41467-025-66926-y
2025 Hemagglutinin-displaying influenza nanovaccines: progress and promise Nanomedicine 10.1080/17435889.2025.2598329
2025 Immunological and virological questions for H5N1 pandemic emergence ImmunoHorizons 10.1093/immhor/vlaf062
2025 Experimental and computational approaches to adaptive viral evolution: Linking molecular variation to phenotypic outcomes Journal of Microbiological Methods 10.1016/j.mimet.2025.107379
2026 Influenza hemagglutinin subtypes have different sequence constraints despite sharing extremely similar structures bioRxiv (Cold Spring Harbor Laboratory) 10.64898/2026.01.05.697808
2026 Loss of α2,3-linked sialoside in the receptor-binding site of a H5N1 influenza hemagglutinin identified in a human patient bioRxiv (Cold Spring Harbor Laboratory) 10.64898/2026.01.19.700419
2026 Clonal interference and changing selective pressures shape the escape of SARS-CoV-2 from hundreds of antibodies Virus Evolution 10.1093/ve/veaf104
2026 Functional and antigenic constraints on the Nipah virus fusion protein Proceedings of the National Academy of Sciences 10.1073/pnas.2529505123
2026 Stabilization of the H5 clade 2.3.4.4b hemagglutinin improves vaccine-elicited neutralizing antibody responses in mice Science Translational Medicine 10.1126/scitranslmed.aea8770
2026 Evaluation of an H5 influenza virus mRNA-lipid nanoparticle (LNP) vaccine in lactating dairy cows bioRxiv (Cold Spring Harbor Laboratory) 10.64898/2026.03.03.709308
2026 H5N1 2.3.4.4b HA E190D and Q226H mutations, picked up as minority variants in a patient, result in an inability to bind sialic acid bioRxiv (Cold Spring Harbor Laboratory) 10.64898/2026.03.06.710037