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

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By G.M.

Significance

We explored how H5Nx influenza viruses, which can infect many different birds and mammals, could adapt to infect humans by altering the hemagglutinin (HA). HA must change to bind human-type receptors for transmission between people. We compared two strains from viruses isolated in 2016 and found that one (2.3.4.4e) can switch to human receptor binding with a single mutation, while another (2.3.4.4b) might require more complex changes to bind simple human-type receptors. These findings highlight the potential for specific strains to evolve and become a pandemic threat, underscoring the importance of monitoring mutations that could lead to human-type receptor adaptation.


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.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/10.1073/pnas.2419800122

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