Infectious Diseases 2025

Infectious Diseases 2025

Receptor binding and tissue tropism of cattle-infecting H5N1 influenza

Cell 188, 1–11 | February 20, 2025 23 January, 2025

A recent study published in Cell elucidates the receptor-binding properties of the H5N1 avian influenza virus that infects cattle, revealing its potential risks to both animal and public health, particularly in light of recent cattle outbreaks.
The article investigates the complex mechanisms through which the H5N1 avian influenza virus (AIV) interacts with host tissues, specifically in cattle. The study centers on the hemagglutinin (HA) protein, analyzing its receptor-binding characteristics, structural properties, and implications for cross-species transmission. Given the zoonotic potential of H5N1, a comprehensive understanding of these mechanisms is crucial for evaluating the associated risks to both animal and human populations.
The research confirms that H5N1 hemagglutinin exhibits a strong binding affinity for sialic acid receptors present in cattle, indicating a significant risk for cross-species transmission. While the virus predominantly binds to avian-like α2-3 sialic acid receptors, it also demonstrates a slight affinity for human-like α2-6 sialic acid receptors.
The findings indicate that the binding of bovine H5N1 hemagglutinin (HA) to human receptors remains relatively weak compared to its binding to avian receptors. Nonetheless, even minimal binding could enhance the virus's capacity to attach to human tissues, potentially increasing its pathogenicity.
Immunohistochemical staining experiments revealed that bovine H5N1 HA could bind to human tissues, including bronchioles, lungs, mammary glands, and conjunctiva. This suggests that the virus possesses the potential to infect human tissues, raising concerns regarding its zoonotic transmission. Overall, while the H5N1 virus demonstrates a preference for avian receptors, the observed binding to human receptors, albeit weak, underscores the necessity for continued surveillance and research to evaluate the virus's transmission potential and associated public health risks.