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Nat Commun . Dominant substitutions underlying the antigenic evolution of H5 influenza virus

tetano

Editor, Senior Moderator
Nat Commun


. 2025 Nov 28;16(1):10708.
doi: 10.1038/s41467-025-65730-y. Dominant substitutions underlying the antigenic evolution of H5 influenza virus

Mengyi Zhang[SUP] #[/SUP][SUP] 1 2 [/SUP], Luyao Qin[SUP] #[/SUP][SUP] 3 4 [/SUP], Zichen Li[SUP] 1 [/SUP], Jiamin Chen[SUP] 1 [/SUP], Jincheng Tong[SUP] 1 [/SUP], Xiao Ding[SUP] 3 4 [/SUP], Huan Li[SUP] 1 [/SUP], Yun Ma[SUP] 3 [/SUP], Jingze Liu[SUP] 3 [/SUP], Qiuju He[SUP] 1 [/SUP], Rong Bi[SUP] 1 [/SUP], Weijin Huang[SUP] 2 5 [/SUP], Cheng Bian[SUP] 1 [/SUP], Youchun Wang[SUP] 6 [/SUP], Aiping Wu[SUP] 7 8 [/SUP], Qianqian Li[SUP] 9 [/SUP]



Affiliations
Abstract

Highly pathogenic avian influenza (HPAI) H5 viruses have recently been documented in mammals including humans, posing a major threat to global public health. To prevent a potential H5 pandemic, it is critical to elucidate the antigenic evolutionary pattern and identify key drivers underlying its evolution. In this work, we construct a comprehensive antigenic map of H5 influenza viruses spanning their evolutionary history and classified three antigenic clusters with no cross-neutralization. The first corresponds to ancestral clades, the second to 2.3.4.4* clades being predominant since 2010, and the third to 2.3.4.4 h clade. Despite the gradually increasing genetic distances from ancestral to 2.3.4.4* to 2.3.4.4 h, their antigenic evolution does not follow the same progressive pattern: the antigenic distance between 2.3.4.4 h and ancestral is smaller than that between 2.3.4.4* and ancestral. This divergence is associated with two distinct mutation patterns at six key amino acid positions: (1) persistent mutations at positions 88 (N > R > S), 199 (D > N > S), and 205 (K > N > D), and (2) reversible mutations at positions 131 (Q > L > Q), 139 (S > P > S), and 289 (N > H > N). These findings not only reveal the antigenic evolution mechanism of H5 influenza, but also provide important guidance for vaccine strain selection and broad-spectrum vaccine development.


 
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