ArticlePLoS pathogens2021
Relationship between hemagglutinin stability and influenza virus persistence after exposure to low pH or supraphysiological heating.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- 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
- Divergent pathogenic mechanisms of influenza A and influenza B viruses.Archives of microbiology · 2026Review
- New determinant of influenza hemagglutinin cleavability identified through random mutagenesis for acid-stabilizing mutations.Microbiology spectrum · 2026Article
- Identification of thermostability-enhancing mutations in H9N2 avian influenza virus hemagglutinin.Journal of virology · 2026Article
- Article
- Bioinformatics-guided vaccine targeting the hemagglutinin protein of avian influenza virus.Molecular genetics and genomics : MGG · 2026Article
- Stability of the two enveloped viruses NDV LaSota and YF-ZIKprM/E to support process development.PloS one · 2026Article
- The haemagglutinin gene of bovine-origin H5N1 influenza viruses currently retains receptor-binding and pH-fusion characteristics of avian host phenotype.Emerging microbes & infections · 2025Article
- Eurasian 1C swine influenza A virus exhibits high pandemic risk traits.Emerging microbes & infections · 2025Article
- Isoleucine at position 137 of haemagglutinin acts as a mammalian adaptation marker of H9N2 avian influenza virus.Emerging microbes & infections · 2025Article
- Emergence of a novel reassortant H3N3 avian influenza virus with enhanced pathogenicity and transmissibility in chickens in China.Veterinary research · 2025Article
- Enhanced and Prolonged Immunogenicity in Mice of Thermally Stabilized Fatty Acid-Conjugated Vaccine Antigen.Vaccines · 2025Article
- Rapid risk assessment to address emerging concerns of HPAI in raw and pasteurized milk.PloS one · 2025Article
- Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance.PLoS biology · 2024Article
- Characterization of human tibrovirus envelope glycoproteins.Journal of virology · 2024Article
- Exploring Potential Intermediates in the Cross-Species Transmission of Influenza A Virus to Humans.Viruses · 2024Review
- Cross-species spill-over potential of the H9N2 bat influenza A virus.Nature communications · 2024Article
- Bis-Benzylisoquinoline Alkaloids Inhibit Porcine Epidemic Diarrhea Virus by Disrupting Virus Entry.Pathogens (Basel, Switzerland) · 2023Article
- Rapid evolution of A(H5N1) influenza viruses after intercontinental spread to North America.Nature communications · 2023Article
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3 authors.
Funding
Abstract
The hemagglutinin (HA) surface glycoprotein is triggered by endosomal low pH to cause membrane fusion during influenza A virus (IAV) entry yet must remain sufficiently stable to avoid premature activation during virion transit between cells and hosts. HA activation pH and/or virion inactivation pH values less than pH 5.6 are thought to be required for IAV airborne transmissibility and human pandemic potential. To enable higher-throughput screening of emerging IAV strains for "humanized" stability, we developed a luciferase reporter assay that measures the threshold pH at which IAVs are inactivated. The reporter assay yielded results similar to TCID50 assay yet required one-fourth the time and one-tenth the virus. For four A/TN/09 (H1N1) HA mutants and 73 IAVs of varying subtype, virion inactivation pH was compared to HA activation pH and the rate of inactivation during 55°C heating. HA stability values correlated highly with virion acid and thermal stability values for isogenic viruses containing HA point mutations. HA stability also correlated with virion acid stability for human isolates but did not correlate with thermal stability at 55°C, raising doubt in the use of supraphysiological heating assays. Some animal isolates had virion inactivation pH values lower than HA activation pH, suggesting factors beyond HA stability can modulate virion stability. The coupling of HA activation pH and virion inactivation pH, and at a value below 5.6, was associated with human adaptation. This suggests that both virologic properties should be considered in risk assessment algorithms for pandemic potential.
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