Santos Jefferson J S, Wang Shengyang, McBride Ryan, Zhao Yan, Paulson James C, Hensley Scott E
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Molecular Medicine and Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA, USA.
bioRxiv. 2024 Aug 2:2024.08.01.606177. doi: 10.1101/2024.08.01.606177.
Clade 2.3.4.4b highly pathogenic H5N1 avian influenza (HPAI) viruses started circulating widely in lactating dairy cattle in the United States at the end of 2023. Avian influenza viruses enter cells after binding to glycan receptors with terminally linked α2-3 sialic acid, whereas human influenza viruses typically bind to glycan receptors terminally linked α2-6 sialic acid in the upper respiratory tract. Here, we evaluated the receptor binding properties of hemagglutinin (HA) trimers from a clade 2.3.4.4b avian isolate (A/American Wigeon/South Carolina/22-000345-001/2021) and a cattle isolate (A/dairy cattle/Texas/24-008749-002-v/2024). Using two different methods, we found that both of the 2.3.4.4b H5s bound efficiently to glycan receptors with terminally linked α2-3 sialic acid with no detectable binding to glycan receptors with terminally linked α2-6 sialic acid. Our data suggest that clade 2.3.4.4b H5N1 viruses bind poorly to human receptors. It will be important to continue evaluating receptor binding properties of these viruses as they evolve in cattle.
2.3.4.4b分支高致病性H5N1禽流感（HPAI）病毒于2023年底开始在美国泌乳奶牛中广泛传播。禽流感病毒在与末端连接α2-3唾液酸的聚糖受体结合后进入细胞，而人流感病毒通常在上呼吸道与末端连接α2-6唾液酸的聚糖受体结合。在此，我们评估了一株2.3.4.4b分支禽类分离株（A/美洲绿头鸭/南卡罗来纳州/22-000345-001/2021）和一株牛分离株（A/奶牛/得克萨斯州/24-008749-002-v/2024）的血凝素（HA）三聚体的受体结合特性。使用两种不同方法，我们发现这两种2.3.4.4b H5均能有效结合末端连接α2-3唾液酸的聚糖受体，而未检测到与末端连接α2-6唾液酸的聚糖受体的结合。我们的数据表明，2.3.4.4b分支H5N1病毒与人类受体的结合较差。随着这些病毒在牛体内进化，持续评估它们的受体结合特性将很重要。
