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Genetic and biological characterization of a duck-origin clade 2.3.4.4b H5N6 avian influenza virus reveals partial mammalian adaptation

delete2026-04-01
delete0
PRE
AI
Z
Zhang, Xinlan
C
Chen, Jing
G
Ge, Zhichuang
C
Chen, Yu
H
Hu, Shunlin
L
Liu, Kaituo
W
Wang, Xiaoquan
Z
Zhang, Pinghu
G
Gao, Ruyi
L
Liu, Xiufan
DOI:10.1016/j.vetmic.2026.111014delete
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Abstract

Abstract

En 中文
Clade 2.3.4.4b H5Nx highly pathogenic avian influenza viruses (HPAIVs) have caused extensive outbreaks in poultry worldwide. H5 HPAIVs have caused sporadic but severe human infections in China, representing a persistent zoonotic threat. Here, we identified a duck-origin H5N6 HPAIV (A/Duck/Jiangsu/628/2022) through routine surveillance and assessed its biological characteristics and mammalian pathogenesis. Phylogenetic analysis revealed > 98% nucleotide identity between strain 628 and the concurrent human H5N6 strain A/Yangzhou/125/2022. Molecular characterization identified multiple mammalian adaptation markers: hemagglutinin substitutions (S137A, T160A, T192I) associated with enhanced human receptor binding; neuraminidase mutations (I117T, D198N) linked to reduced neuraminidase inhibitor susceptibility; and polymerase complex changes (PB1-D622G, PA-K142Q) conferring increased mammalian cell replication. In vitro studies demonstrated that 628 virus replicated more efficiently in mammalian than in avian cells and exhibited dual receptor-binding specificity. Mouse pathogenicity assays revealed moderate virulence with progressive lung pathology. Critically, transmission experiments confirmed both direct contact and airborne transmission capabilities of 628 in guinea pigs. These findings demonstrate that circulating H5N6 viruses have acquired partial mammalian adaptation while retaining avian fitness, significantly elevating pandemic potential. Enhanced surveillance of wild bird populations, poultry farms, and live poultry markets is urgently needed to develop effective prevention and control strategies.
Keywords:
Pathogenicity
Transmissibility
Duck-Origin
H5N6

Journal

V
Veterinary Microbiology
IF:
2.7
Papers:
215
Citations:
1.7W

Organization

Y
yangzhou university
Scholars:
7.3K
Papers: 2.3K
Citations: 2
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