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Nature letter - A human isolate of bovine H5N1 is transmissible and lethal in animal models - published October 28, 2024

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Bovine H5N1 influenza from infected worker transmissible and lethal in animal models
  • Article
  • Published: 28 October 2024
A human isolate of bovine H5N1 is transmissible and lethal in animal models
Nature (2024)Cite this article
We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.


Abstract


The outbreak of clade 2.3.4.4b highly pathogenic avian influenza viruses of the H5N1 subtype (HPAI H5N1) in dairy cows in the US has so far resulted in spillover infections of at least thirteen farm workers[SUP]1-3[/SUP], who presented with mild respiratory symptoms or conjunctivitis, and one individual with no known animal exposure who was hospitalized but recovered[SUP]3,4[/SUP]. Here, we characterized A/Texas/37/2024 (huTX37-H5N1), a virus isolated from the eyes of an infected farm worker who developed conjunctivitis[SUP]5[/SUP]. 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 was lethal in mice and ferrets and spread systemically with high titres in respiratory and non-respiratory organs. Importantly, in four independent experiments in ferrets, huTX37-H5N1 transmitted via 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 like that of PB2-627K (encoded by huTX37-H5N1). Additionally, bovine HPAI H5N1 viruses were 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 prior adaptation and causes lethal disease in animal models.​

https://www.nature.com/articles/s41586-024-08254-7
 
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