美国威斯康星大学Yoshihiro Kawaoka课题组发现，人类分离的牛源H5N1在动物模型中具有可传播性和致死性。2024年10月28日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员对从一名出现结膜炎的感染农场工人眼部分离的病毒A/Texas/37/2024（huTX37-H5N1）进行了表征。huTX37-H5N1在原代人肺泡上皮细胞中高效复制，但在角膜上皮细胞中的复制效率较低。

尽管在感染工人中引起轻微疾病，huTX37-H5N1在小鼠和雪貂中致命，并在呼吸和非呼吸器官中以高滴度系统性传播。重要的是，在对雪貂进行的四个独立实验中，huTX37-H5N1通过呼吸飞沫在17%–33%的传播对中传播，且六只暴露的雪貂中有五只感染后死亡。

PB2-631L（由牛源分离株编码）在人体细胞中促进了流感聚合酶活性，提示其在哺乳动物适应中的作用，类似于由huTX37-H5N1编码的PB2-627K。此外，牛源HPAI H5N1病毒在体外和小鼠中对聚合酶抑制剂均表现出敏感性。因此，来自乳牛的HPAI H5N1病毒在哺乳动物中通过呼吸飞沫传播，无需先前适应，且在动物模型中引起致命疾病。

据了解，在美国，2.3.4.4b高致病性禽流感H5N1亚型病毒（HPAI H5N1）在乳牛中的暴发至今已导致至少十三名农场工人发生溢出感染，这些工人出现了轻微的呼吸症状或结膜炎，其中一名没有已知动物接触史的个体住院治疗但已康复。

附：英文原文

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

Author: 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

Issue&Volume: 2024-10-28

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 workers1-3, 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 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.

DOI: 10.1038/s41586-024-08254-7

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