2026/06/19 by Satya Srinivas, Shubhada K. Chothe, Santhamani Ramasamy +9 · 1 voice
Medicine · Agricultural and Biological Sciences · Immunology and Microbiology · #Influenza Virus Research Studies #Animal Disease Management and Epidemiology #Poxvirus research and outbreaks
paper · pdf · doi:10.1126/sciadv.aea2068
openalex publication_date 2026/06/19 · openalex created_date 2026/06/20 · openalex updated_date 2026/07/27
The unusual tropism of H5N1 clade 2.3.4.4b for cattle mammary glands, causing necrotizing mastitis without major respiratory involvement, raises critical questions about its underlying mechanisms. We conducted glycomics and linkage-specific lectin histochemistry to characterize sialic acid (SA) receptor diversity and anatomical distribution, and virus binding assays and high-resolution electron microscopy (EM) to visualize virus-receptor interactions. Cattle mammary gland exhibited an abundance of N- and O-linked SA glycans, showing a stronger binding affinity to clade 2.3.4.4b H5 than clade 2.2 H5. In contrast, the cattle trachea contained only O-linked but not N-linked SAs and showed no detectable H5 binding, indicating limited compatible influenza A virus (IAV) receptor availability in the tracheal epithelium. EM of virus-bound tissues further validated the receptor basis of H5N1 infection in cattle. As H5N1 continues infecting unusual hosts, as evidenced by the first case in sheep, our study offers a methodological framework for assessing IAV susceptibility.