Receptor binding, structure, and tissue tropism of cattle-infecting H5N1 avian influenza virus hemagglutinin

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Pub Date : 2025-01-23 DOI:10.1016/j.cell.2025.01.019

Hao Song, Tianjiao Hao, Pu Han, Haichen Wang, Xu Zhang, Xiaomei Li, Yuxuan Wang, Jiamin Chen, Ying Li, Xiyue Jin, Xuefeng Duan, Wei Zhang, Yuhai Bi, Ronghua Jin, Lei Sun, Ningli Wang, George F. Gao

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引用次数: 0

Abstract

The ongoing circulation of highly pathogenic avian influenza (HPAI) A (H5N1) viruses, particularly clade 2.3.4.4b strains, poses a significant threat to animal and public health. Recent outbreaks in cattle highlight concerns about cross-species transmission and zoonotic spillover. Here, we found that the hemagglutinin (HA) protein from a cattle-infecting H5N1 virus has acquired slight binding to human-like α2-6-linked receptors while still exhibiting a strong preference for avian-like α2-3-linked sialic acid receptors. Immunohistochemical staining revealed HA binding to bovine pulmonary and mammary tissues, aligning with clinical observations. HA also binds effectively to human conjunctival, tracheal, and mammary tissues, indicating a risk for human transmission, notably in cases of conjunctivitis. High-resolution cryo-electron microscopy (cryo-EM) structures of this H5 HA in complex with either α2-3 or α2-6 receptors elucidate the molecular mechanisms underlying its receptor-binding properties. These findings provide critical insights into the tropism and transmission potential of this emerging pathogen.

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牛感染H5N1禽流感病毒血凝素的受体结合、结构和组织趋向性

高致病性禽流感（HPAI） A （H5N1）病毒的持续传播，特别是2.3.4.4b进化枝毒株，对动物和公众健康构成重大威胁。最近在牛中爆发的疫情突出了对跨物种传播和人畜共患病溢出的担忧。在这里，我们发现来自牛感染H5N1病毒的血凝素（HA）蛋白与人样α2-6连接受体轻微结合，但仍然对鸟样α2-3连接的唾液酸受体表现出强烈的偏好。免疫组织化学染色显示透明质酸与牛肺和乳腺组织结合，与临床观察相符。透明质酸还能与人类结膜、气管和乳腺组织有效结合，这表明它有人类传播的风险，特别是在结膜炎的情况下。该H5 HA与α2-3或α2-6受体复合物的高分辨率冷冻电镜（cryo-EM）结构阐明了其受体结合特性的分子机制。这些发现为了解这种新出现的病原体的倾向和传播潜力提供了重要的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.