Enhanced Human-Type Receptor Binding by Ferret-Transmissible H5N1 with a K193T Mutation

Journal of Virology
Wenjie PengRobert P de Vries

Abstract

All human influenza pandemics have originated from avian influenza viruses. Although multiple changes are needed for an avian virus to be able to transmit between humans, binding to human-type receptors is essential. Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets. Upon detailed analysis, we have found that these mutants exhibit significant differences in fine receptor specificity compared to human H1N1 and H3N2 and retain avian-type receptor binding. We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer. In this binding mode, the glycan projects over the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193. Thus, we hypothesized that a K193T mutation would improve binding to branched N-linked receptors. Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trache...Continue Reading

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Citations

Aug 14, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Brian R WasikColin R Parrish
Nov 5, 2020·The Journal of Biological Chemistry·Andrew J Thompson, James C Paulson
Jun 13, 2019·Cell Reports·Frederik BroszeitRobert P de Vries

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