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Avian-to-Human Receptor-Binding Adaptation by Influenza A Virus Hemagglutinin H4.

Song H, Qi J, Xiao H, Bi Y, Zhang W, Xu Y, Wang F, Shi Y, Gao GF
Cell Rep 20 1201-1214 (2017)
Related entries: 5xl1, 5xl2, 5xl3, 5xl4, 5xl5, 5xl6, 5xl8, 5xl9, 5xla, 5xlb, 5xlc, 5xld

Cited: 39 times
EuropePMC logo PMID: 28768203

Abstract

Low-pathogenicity avian influenza viruses (LPAIVs) have caused a global concern to public health since the first novel LPAIV H7N9 outbreak occurred. The receptor-binding properties of the viral hemagglutinin are one key factor for efficient transmission and infection in humans. Recent evidence shows that H4 subtype viruses have been widely circulating in domestic poultry and human asymptomatic infections might have occurred. Here, we evaluated the receptor-binding properties of two representative isolates, avian H4N6 (containing Q226 and G228) and swine H4N6 (containing L226 and S228), and found that the avian isolate preferentially binds to avian receptors, whereas the swine isolate preferentially binds to human receptors. The Q226L and G228S substitutions are pivotal for the receptor-binding switch, which resulted in similar human receptor-binding features to the pandemic H2 and H3, implying that H4 has the potential to cause human infections. This early-warning study calls for future extensive surveillance.

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  1. Influenza A Virus Agnostic Receptor Tropism Revealed Using a Novel Biological System with Terminal Sialic Acid Knockout Cells. Kamiki H, Murakami S, Nishikaze T, Hiono T, Igarashi M, Furuse Y, Matsugo H, Ishida H, Katayama M, Sekine W, Muraki Y, Takahashi M, Takenaka-Uema A, Horimoto T. J Virol 96 e0041622 (2022)


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  1. Influenza Hemagglutinin and Neuraminidase: Yin⁻Yang Proteins Coevolving to Thwart Immunity. Kosik I, Yewdell JW. Viruses 11 E346 (2019)
  2. Inventory of molecular markers affecting biological characteristics of avian influenza A viruses. Suttie A, Deng YM, Greenhill AR, Dussart P, Horwood PF, Karlsson EA. Virus Genes 55 739-768 (2019)
  3. Influenza Hemagglutinin Structures and Antibody Recognition. Wu NC, Wilson IA. Cold Spring Harb Perspect Med 10 a038778 (2020)
  4. Structural insights into the design of novel anti-influenza therapies. Wu NC, Wilson IA. Nat Struct Mol Biol 25 115-121 (2018)
  5. Emerging HxNy Influenza A Viruses. Liu WJ, Wu Y, Bi Y, Shi W, Wang D, Shi Y, Gao GF. Cold Spring Harb Perspect Med 12 a038406 (2022)
  6. Structural Biology of Influenza Hemagglutinin: An Amaranthine Adventure. Wu NC, Wilson IA. Viruses 12 E1053 (2020)
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  8. Avian Influenza Virus Tropism in Humans. AbuBakar U, Amrani L, Kamarulzaman FA, Karsani SA, Hassandarvish P, Khairat JE. Viruses 15 833 (2023)
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  10. The H4 subtype of avian influenza virus: a review of its historical evolution, global distribution, adaptive mutations and receptor binding properties. Liu J, Liang Z, Sun W, Hua W, Huang S, Wen F. Poult Sci 103 103913 (2024)

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