bioRxiv preprint January 17, 2026
19 January 2026
In recent years, highly pathogenic avian influenza (HPAI) viruses of the H5N1 clade 2.3.4.4b have spread globally, resulting in unprecedented mortality rates among wild birds and poultry. Beyond its devastating impact on avian populations, the virus has increasingly crossed the species barrier to infect various mammals. In early 2024, a significant spillover event was documented for the first time in U.S. dairy cattle. While human infections associated with this outbreak have remained limited and clinically mild thus far, significant concerns have arisen regarding the virus's potential to adapt for efficient replication within the human upper respiratory tract.
A study conducted by a European research group evaluated the replication kinetics of the H5N1 strain isolated from dairy cattle in Texas (Genotype B3.13). The researchers utilized primary human nasal epithelial (HNE) cell cultures, which serve as a highly relevant ex vivo model for studying the dynamics of the human upper respiratory system.
The study’s findings reveal that the bovine-derived H5N1 virus replicates in human nasal cells with an efficiency comparable to that of the 2009 H1N1 pandemic influenza virus, reaching exceptionally high viral titers. Critically, while previous avian influenza strains typically required a temperature of 37°C for optimal replication, the bovine-derived strain demonstrated robust replication at 33°C, the ambient temperature of the human nasal cavity. This adaptability is further supported by the fact that human nasal cells naturally express both avian-type (alpha2,3-linked) and mammalian-type (alpha2,6-linked) sialic acid receptors. Furthermore, the infection resulted in a significant loss of ciliated epithelial cells, a cornerstone of the respiratory system's innate defense, at a rate exceeding that of the 2009 H1N1 pandemic strain.
These data underscore a profound scientific inconsistency and a stark discrepancy in U.S. governmental policy across different agricultural sectors. While the detection of the avian influenza virus in poultry flocks triggers immediate culling, even for strains with limited human adaptation, the management of dairy cattle remains fundamentally different. To date, infected dairy herds are not subject to culling, despite mounting scientific evidence indicating the high zoonotic potential of this specific strain and its remarkable replication efficiency in human tissues.
