ArticlePLoS pathogens2011
Acid stability of the hemagglutinin protein regulates H5N1 influenza virus pathogenicity.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 131 citations in OpenAlex.
- An In Vitro Screen Identifies H1 Influenza Hemagglutinin Substitutions That Alter mRNA-LNP Vaccine Responses Against the Stalk Domain.Vaccines · 2026Article
- Host switching mutations in H5N1 influenza hemagglutinin suppress site-specific activation dynamics.Nature communications · 2025Article
- Host Switching Mutations in H5N1 Influenza Hemagglutinin Suppress Site-specific Activation Dynamics.bioRxiv : the preprint server for biology · 2025Article
- Review
- Genetic Evolution of the Hemagglutinin Genes of Seasonal Influenza A Viruses in Türkiye Between 2017 and 2023.Influenza and other respiratory viruses · 2025Article
- Deglycosylation and truncation in the neuraminidase stalk are functionally equivalent in enhancing the pathogenicity of a high pathogenicity avian influenza virus in chickens.Journal of virology · 2025Article
- Emergence of a novel reassortant H3N3 avian influenza virus with enhanced pathogenicity and transmissibility in chickens in China.Veterinary research · 2025Article
- First contact: an interdisciplinary guide into decoding H5N1 influenza virus interactions with glycosaminoglycans in 3D respiratory cell models.Frontiers in cellular and infection microbiology · 2025Review
- The host tropism of current zoonotic H7N9 viruses depends mainly on an acid-labile hemagglutinin with a single amino acid mutation in the stalk region.PLoS pathogens · 2024Article
- Article
- Hemagglutinin and neuraminidase of a non-pathogenic H7N7 avian influenza virus coevolved during the acquisition of intranasal pathogenicity in chickens.Archives of virology · 2024Article
- Potential cross-species transmission of highly pathogenic avian influenza H5 subtype (HPAI H5) viruses to humans calls for the development of H5-specific and universal influenza vaccines.Cell discovery · 2023Review
- Key amino acid position 272 in neuraminidase determines the replication and virulence of H5N6 avian influenza virus in mammals.iScience · 2022Article
- Article
- Hemagglutinin Subtype Specificity and Mechanisms of Highly Pathogenic Avian Influenza Virus Genesis.Viruses · 2022Review
- Emerging of H5N6 Subtype Influenza Virus with 129-Glycosylation Site on Hemagglutinin in Poultry in China Acquires Immune Pressure Adaption.Microbiology spectrum · 2022Article
- Evolutionary pressures rendered by animal husbandry practices for avian influenza viruses to adapt to humans.iScience · 2022Review
- Swine H1N1 Influenza Virus Variants with Enhanced Polymerase Activity and HA Stability Promote Airborne Transmission in Ferrets.Journal of virology · 2022Article
- Selection of an Optimal Recombinant Egyptian H9N2 Avian Influenza Vaccine Strain for Poultry with High Antigenicity and Safety.Vaccines · 2022Article
- Amino acid substitutions in the H5N1 avian influenza haemagglutinin alter pH of fusion and receptor binding to promote a highly pathogenic phenotype in chickens.The Journal of general virology · 2021Article
28 more citing papers are in PubMed but not listed here.
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6 authors at 1 institution in 1 country.
Funding
Abstract
Highly pathogenic avian influenza viruses of the H5N1 subtype continue to threaten agriculture and human health. Here, we use biochemistry and x-ray crystallography to reveal how amino-acid variations in the hemagglutinin (HA) protein contribute to the pathogenicity of H5N1 influenza virus in chickens. HA proteins from highly pathogenic (HP) A/chicken/Hong Kong/YU562/2001 and moderately pathogenic (MP) A/goose/Hong Kong/437-10/1999 isolates of H5N1 were found to be expressed and cleaved in similar amounts, and both proteins had similar receptor-binding properties. However, amino-acid variations at positions 104 and 115 in the vestigial esterase sub-domain of the HA1 receptor-binding domain (RBD) were found to modulate the pH of HA activation such that the HP and MP HA proteins are activated for membrane fusion at pH 5.7 and 5.3, respectively. In general, an increase in H5N1 pathogenicity in chickens was found to correlate with an increase in the pH of HA activation for mutant and chimeric HA proteins in the observed range of pH 5.2 to 6.0. We determined a crystal structure of the MP HA protein at 2.50 Å resolution and two structures of HP HA at 2.95 and 3.10 Å resolution. Residues 104 and 115 that modulate the acid stability of the HA protein are situated at the N- and C-termini of the 110-helix in the vestigial esterase sub-domain, which interacts with the B loop of the HA2 stalk domain. Interactions between the 110-helix and the stalk domain appear to be important in regulating HA protein acid stability, which in turn modulates influenza virus replication and pathogenesis. Overall, an optimal activation pH of the HA protein is found to be necessary for high pathogenicity by H5N1 influenza virus in avian species.
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