H5N1 avian influenza in dairy cattle: Molecular adaptation, transmission mechanisms, and control strategies.

Since 2024, highly pathogenic H5N1 avian influenza virus (HPAIV) has caused widespread outbreaks in dairy cattle in the United States, representing a significant expansion in its mammalian host range. This epizootic has resulted in clinical diseases, including mastitis, and substantial economic losses, while also posing a major public health threat due to the establishment of distinct transmission chains linking wild birds, cattle, the environment, and humans. This review synthesizes findings from studies published between 2024 and 2026, including data from the United States, China, and Europe. It examines the molecular basis for mammalian adaptation, focusing on key polymerase mutations. It analyzes the receptor-binding properties of the viral hemagglutinin, which retains strong avian-type receptor preference while exhibiting limited binding to human tissues. Furthermore, it explores non-respiratory transmission routes, primarily "mouth-to-teat" behavioral spread and mechanical transmission via contaminated milk. The review also assesses the ongoing risk of cross-species transmission associated with viral evolution and discusses current challenges and strategies in surveillance, animal vaccine development, farm biosecurity, and dairy product safety management. By integrating multidisciplinary evidence, this review aims to provide a scientific foundation for building an effective "One Health" control framework.