tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 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[SUP] 1 [/SUP], Ting-Hui Lin[SUP] 2 [/SUP], Xueyong Zhu[SUP] 2 [/SUP], Alba Gabarroca García[SUP] 1 [/SUP], Elif Uslu[SUP] 1 [/SUP], Ruonan Liang[SUP] 1 [/SUP], Cindy M Spruit[SUP] 1 [/SUP], Mathilde Richard[SUP] 3 [/SUP], Geert-Jan Boons[SUP] 1 4 [/SUP], Ian A Wilson[SUP] 2 5 [/SUP], Robert P de Vries[SUP] 1 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], Ting-Hui Lin[SUP] 2 [/SUP], Xueyong Zhu[SUP] 2 [/SUP], Alba Gabarroca García[SUP] 1 [/SUP], Elif Uslu[SUP] 1 [/SUP], Ruonan Liang[SUP] 1 [/SUP], Cindy M Spruit[SUP] 1 [/SUP], Mathilde Richard[SUP] 3 [/SUP], Geert-Jan Boons[SUP] 1 4 [/SUP], Ian A Wilson[SUP] 2 5 [/SUP], Robert P de Vries[SUP] 1 [/SUP]
Affiliations
- PMID: 40232794
- DOI: 10.1073/pnas.2419800122
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.