A recent study has found that a single alteration in the protein on the surface of the highly pathogenic avian influenza (HPAI) H5N1 virus, which is currently present in U.S. dairy cows, might make it easier to spread among humans. This research highlights the critical need for ongoing careful monitoring and surveillance of the HPAI H5N1 virus to detect any genetic changes that could enhance its transmissibility in humans.
New research backed by the National Institutes of Health (NIH) and published in the journal Science indicates that a single change in the protein on the surface of the HPAI H5N1 influenza virus—now found in U.S. dairy cows—might facilitate human transmission. These findings underscore the necessity for continued, careful surveillance of HPAI H5N1 to identify possible genetic variations that could enhance the virus’s ability to spread among humans.
At present, the H5N1 virus strains affecting cows are not known to transmit between humans. Nevertheless, there have been cases of infection in people who came into contact with infected birds, poultry, dairy cows, and other mammals. As a part of preparedness for potential pandemics, researchers have been tracking the H5N1 virus for several years to understand the viral genetic changes that occur naturally and their potential impact on how easily the virus can spread.
Influenza viruses use a surface protein called hemagglutinin (HA) to attach to cells. This protein connects to sugar (glycan) receptors on cells, which leads to infection. Avian influenza viruses, including H5N1, have not frequently infected humans because the human upper respiratory system lacks the avian-type receptors found in birds. Scientists worry that these viruses could evolve to interact with human-type cell receptors in the upper airways, enabling them to infect and transmit among humans.
Researchers at Scripps Research examined the H5N1 strain taken from the first human case in the U.S. linked to the bovine strain 2.3.4.4b (A/Texas/37/2024) to study how mutations in the HA gene influenced the protein’s ability to bind to avian versus human-type cell receptors. By introducing various mutations previously observed in nature into the viral HA protein, they discovered that one specific mutation, named Q226L, significantly enhanced the protein’s capacity to attach to receptors commonly found on human cells, particularly when accompanied by another mutation. Importantly, these genetic modifications were limited to the HA surface protein, and the researchers did not create or work with a complete, infectious virus.
While the results involving the Q226L mutation raise some concerns, the authors emphasize that this does not indicate an imminent widespread pandemic caused by HPAI H5N1. Additional genetic changes would likely be necessary for the virus to transmit effectively among humans. Given the increase in reported H5N1 human cases due to direct contact with infected animals, these findings highlight the urgency for ongoing outbreak management and genomic monitoring to watch for genetic changes in HPAI H5N1 and to uphold public health preparedness.
This research received funding in part from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) through its Centers of Excellence for Influenza Research and Response program.
