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<p>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 &gt; R &gt; S), 199 (D &gt; N &gt; S), and 205 (K &gt; N &gt; D), and (2) reversible mutations at positions 131 (Q &gt; L &gt; Q), 139 (S &gt; P &gt; S), and 289 (N &gt; H &gt; 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.</p>

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Dominant substitutions underlying the antigenic evolution of H5 influenza virus

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月28日

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  • Mengyi Zhang,
  • Luyao Qin,
  • Zichen Li,
  • Jiamin Chen,
  • Jincheng Tong,
  • Xiao Ding,
  • Huan Li,
  • Yun Ma,
  • Jingze Liu,
  • Qiuju He,
  • Rong Bi,
  • Weijin Huang,
  • Cheng Bian,
  • Youchun Wang,
  • Aiping Wu,
  • Qianqian Li

摘要

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.