Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr 22;122(16):e2419800122.
doi: 10.1073/pnas.2419800122. Epub 2025 Apr 15.

The Q226L mutation can convert a highly pathogenic H5 2.3.4.4e virus to bind human-type receptors

María Ríos Carrasco  1 , Ting-Hui Lin  2 , Xueyong Zhu  2 , Alba Gabarroca García  1 , Elif Uslu  1 , Ruonan Liang  1 , Cindy M Spruit  1 , Mathilde Richard  3 , Geert-Jan Boons  1   4 , Ian A Wilson  2   5 , Robert P de Vries  1
Affiliations

The Q226L mutation can convert a highly pathogenic H5 2.3.4.4e virus to bind human-type receptors

María Ríos Carrasco et al. Proc Natl Acad Sci U S A. .

Abstract

H5Nx viruses continue to wreak havoc in avian and mammalian species worldwide. The virus distinguishes itself by the ability to replicate to high titers and transmit efficiently in a wide variety of hosts in diverse climatic environments. Fortunately, transmission to and between humans is scarce. Yet, if such an event were to occur, it could spark a pandemic as humans are immunologically naïve to H5 viruses. A significant determinant of transmission to and between humans is the ability of the influenza A virus hemagglutinin (HA) protein to shift from an avian-type to a human-type receptor specificity. Here, we demonstrate that a 2016 2.3.4.4e virus HA can convert to human-type receptor binding via a single Q226L mutation, in contrast to a cleavage-modified 2016 2.3.4.4b virus HA. Using glycan arrays, X-ray structural analyses, tissue- and direct glycan binding, we show that L133a Δ and 227Q are vital for this phenotype. Thus, whereas the 2.3.4.4e virus HA only needs a single amino acid mutation, the modified 2016 2.3.4.4b HA was not easily converted to human-type receptor specificity.

Keywords: glycan array; hemagglutinin; influenza A virus; sialic acid.

PubMed Disclaimer

Conflict of interest statement

Competing interests statement:The authors declare no competing interest.

Update of

References

    1. Joseph U., Su Y. C., Vijaykrishna D., Smith G. J., The ecology and adaptive evolution of influenza A interspecies transmission. Influenza Other Respir. Viruses 11, 74–84 (2017). - PMC - PubMed
    1. Karakus U., et al. , H19 influenza A virus exhibits species-specific MHC class II receptor usage. Cell Host Microbe 32, 1089–1102 (2024). - PMC - PubMed
    1. Caserta L. C., et al. , Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle. Nature 634, 669–676 (2024). - PMC - PubMed
    1. Shi J., Zeng X., Cui P., Yan C., Chen H., Alarming situation of emerging H5 and H7 avian influenza and effective control strategies. Emerg. Microbes Infect. 12, 2155072 (2023). - PMC - PubMed
    1. Xu X., Subbarao N. J., Cox Y. Guo., Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong. Virology 261, 15–19 (1999). - PubMed

MeSH terms

Substances

LinkOut - more resources