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

• 成果类型: Article
• 署名作者: Gu, Chunyang; Maemura, Tadashi; Guan, Lizheng; Eisfeld, Amie J.; Biswas, Asim; Kiso, Maki; Uraki, Ryuta; Ito, Mutsumi; Trifkovic, Sanja; Wang, Tong; Babujee, Lavanya; Presler Jr, Robert; Dahn, Randall; Suzuki, Yasuo; Halfmann, Peter J.; Yamayoshi, Seiya; Neumann, Gabriele; Kawaoka, Yoshihiro
• 署名单位: University of Wisconsin System; University of Wisconsin Madison; University of Tokyo; University of Shizuoka; University of Tokyo; Japan Institute for Health Security (JIHS); National Center for Global Health & Medicine - Japan
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4895
• DOI: 10.1038/s41586-024-08254-7
• 发表日期: 2024-12-19
• 关键词: influenza-a virus; ACID; pb2; replication; determinant

摘要

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 workers1, 2-3, who presented with mild respiratory symptoms or conjunctivitis, and one individual with no known animal exposure who was hospitalized but recovered3,4. Here we characterized A/Texas/37/2024 (huTX37-H5N1), a virus isolated from the eyes of an infected farm worker who developed conjunctivitis5. 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.