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A human isolate of bovine H5N1 is transmissible and lethal in animal models

The outbreak of clade 2.3.4.4b highly pathogenic avian influenza viruses of the H5N1 subtype (HPAI H5N1) in dairy cattle in the USA has so far resulted in spillover infections of at least 14 farm workers 1 , 2 – 3 , who presented with mild respiratory symptoms or conjunctivitis, and one individual w...

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Published in:Nature (London) 2024-12, Vol.636 (8043), p.711-718
Main Authors: Gu, Chunyang, Maemura, Tadashi, Guan, Lizheng, Eisfeld, Amie J., Biswas, Asim, Kiso, Maki, Uraki, Ryuta, Ito, Mutsumi, Trifkovic, Sanja, Wang, Tong, Babujee, Lavanya, Presler, Robert, Dahn, Randall, Suzuki, Yasuo, Halfmann, Peter J., Yamayoshi, Seiya, Neumann, Gabriele, Kawaoka, Yoshihiro
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container_title Nature (London)
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creator Gu, Chunyang
Maemura, Tadashi
Guan, Lizheng
Eisfeld, Amie J.
Biswas, Asim
Kiso, Maki
Uraki, Ryuta
Ito, Mutsumi
Trifkovic, Sanja
Wang, Tong
Babujee, Lavanya
Presler, Robert
Dahn, Randall
Suzuki, Yasuo
Halfmann, Peter J.
Yamayoshi, Seiya
Neumann, Gabriele
Kawaoka, Yoshihiro
description The outbreak of clade 2.3.4.4b highly pathogenic avian influenza viruses of the H5N1 subtype (HPAI H5N1) in dairy cattle in the USA has so far resulted in spillover infections of at least 14 farm workers 1 , 2 – 3 , who presented with mild respiratory symptoms or conjunctivitis, and one individual with no known animal exposure who was hospitalized but recovered 3 , 4 . Here we characterized A/Texas/37/2024 (huTX37-H5N1), a virus isolated from the eyes of an infected farm worker who developed conjunctivitis 5 . huTX37-H5N1 replicated efficiently in primary human alveolar epithelial cells, but less efficiently in corneal epithelial cells. Despite causing mild disease in the infected worker, huTX37-H5N1 proved lethal in mice and ferrets and spread systemically, with high titres in both respiratory and non-respiratory organs. Importantly, in four independent experiments in ferrets, huTX37-H5N1 transmitted by respiratory droplets in 17–33% of transmission pairs, and five of six exposed ferrets that became infected died. PB2-631L (encoded by bovine isolates) promoted influenza polymerase activity in human cells, suggesting a role in mammalian adaptation similar to that of PB2-627K (encoded by huTX37-H5N1). In addition, bovine HPAI H5N1 virus was found to be susceptible to polymerase inhibitors both in vitro and in mice. Thus, HPAI H5N1 virus derived from dairy cattle transmits by respiratory droplets in mammals without previous adaptation and causes lethal disease in animal models. A/Texas/37/2024 (huTX37-H5N1), a virus isolated from the eyes of an infected farm worker who developed conjunctivitis, proved lethal in mice and ferrets, spreading systemically with high titres in both respiratory and non-respiratory organs, and transmitted by respiratory droplets in ferrets.
doi_str_mv 10.1038/s41586-024-08254-7
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Here we characterized A/Texas/37/2024 (huTX37-H5N1), a virus isolated from the eyes of an infected farm worker who developed conjunctivitis 5 . huTX37-H5N1 replicated efficiently in primary human alveolar epithelial cells, but less efficiently in corneal epithelial cells. Despite causing mild disease in the infected worker, huTX37-H5N1 proved lethal in mice and ferrets and spread systemically, with high titres in both respiratory and non-respiratory organs. Importantly, in four independent experiments in ferrets, huTX37-H5N1 transmitted by respiratory droplets in 17–33% of transmission pairs, and five of six exposed ferrets that became infected died. PB2-631L (encoded by bovine isolates) promoted influenza polymerase activity in human cells, suggesting a role in mammalian adaptation similar to that of PB2-627K (encoded by huTX37-H5N1). In addition, bovine HPAI H5N1 virus was found to be susceptible to polymerase inhibitors both in vitro and in mice. 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subjects 13/106
45/23
631/326/596/1578
631/326/596/2555
631/326/596/2563
64/60
Animals
Cattle
Disease Models, Animal
Female
Ferrets - virology
Humanities and Social Sciences
Humans
Influenza A Virus, H5N1 Subtype - isolation & purification
Influenza A Virus, H5N1 Subtype - pathogenicity
Influenza, Human - transmission
Influenza, Human - virology
Male
Mice
multidisciplinary
Orthomyxoviridae Infections - transmission
Orthomyxoviridae Infections - virology
RNA-Dependent RNA Polymerase - metabolism
Science
Science (multidisciplinary)
Virus Replication
title A human isolate of bovine H5N1 is transmissible and lethal in animal models
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