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Influenza A (H6N6) virus isolated from chickens replicate in mice and human lungs without prior adaptation
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  • Lingxi Gao,
  • Xijing Wang,
  • Yugui Lin,
  • Weijuan Zhong,
  • Shanggui Su,
  • Siyu Zhou,
  • Yinchuan Zhu,
  • Chengyi Li,
  • Xiaohui Fan,
  • Zengfeng Zhang
Lingxi Gao
Guangxi Medical University
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Xijing Wang
Guangxi Medical University
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Yugui Lin
Guangxi Medical University
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Weijuan Zhong
Guangxi Medical University
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Shanggui Su
Guangxi Medical University
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Siyu Zhou
Guangxi Medical University
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Yinchuan Zhu
Guangxi Medical University
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Chengyi Li
Guangxi Medical University
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Xiaohui Fan
Guangxi Medical University
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Zengfeng Zhang
Guangxi Medical University
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Abstract

H6H6 subtype avian influenza virus (AIV) is currently prevalent in wild birds and poultry. Its host range has gradually expanded to the mammals, such as swine. Some strains of H6N6 AIV have even acquired the ability to bind to human-like receptors SA-α2, 6Gal, thus increasing the risk of animal-human transmission. To investigate whether H6N6 AIV can cross interspecies barriers from poultry to mammals and even humans, we assessed the molecular characteristics, receptor-binding preference, replication in mice, and the human lung of three chicken-originated H6N6 strains. Among the three chicken-originated H6N6 strains, A/CK/ZZ/346/2014 (ZZ346) virus with P186T, H156R, S263G mutation of hemagglutinin (HA) showed the ability to bind to avian-like SAα-2,3Gal and human-like SAα-2,6Gal receptors. Moreover, H6N6 viruses, especially the ZZ346 strain, could replicate and infect mice and human lungs. Our study detected the H6N6 virus favorable to bind to both avian-like SAα-2,3Gal and human-like SAα-2,6Gal receptors, verified its ability to cross the species barrier to infect mice, and verified to infect human lungs without prior adaptation. This study emphasizes the importance of continuous and intense monitoring of the evolution of the H6N6 virus in the terrestrial bird.