A single modification to the protein found on the surface of the H5N1 highly pathogenic avian influenza (HPAI) virus currently circulating in U.S. dairy cows could allow for easier transmission between humans, according to new research. funded by the National Institutes of Health (NIH) and published today in the journal Science. The study results reinforce the need for continued vigilant surveillance and monitoring of HPAI H5N1 to detect possible genetic changes that could make the virus more transmissible in humans.
Current strains of bovine (cow) H5N1 virus are not known to be transmissible between people; However, infections have occurred in people exposed to infected wild birds, poultry, dairy cows, and other mammals. As part of pandemic preparedness efforts, researchers have monitored the H5N1 virus for years to understand viral genetic mutations that occur in nature and what impact they may have on transmissibility.
Influenza viruses attach to cells with a viral surface protein called hemagglutinin (HA). HA attaches to receptors for sugar molecules (glycan) on cells to cause infection. Avian (bird) influenza viruses, such as H5N1, have not infected people frequently because the human upper respiratory tract lacks the avian-type cell receptors found in birds. Scientists are concerned that viruses could evolve to recognize human-type cell receptors in the upper respiratory tract and gain the ability to infect people and spread between them.
Scripps Research scientists used the H5N1 strain isolated from the first human infection in the US with bovine strain 2.3.4.4b (A/Texas/37/2024) to test how mutations in the HA gene sequence affected the binding of that protein with birds versus human-type cell receptors. The researchers introduced several mutations into the viral HA protein that had been observed to occur naturally in the past and found that one mutation, called Q226L, improved the protein’s ability to bind to receptors normally found on human cells, especially when an additional mutation was present. Importantly, the researchers introduced the genetic mutations only into the HA surface protein and did not create or perform experiments with a complete infectious virus.
The authors note that the experimental finding with the Q226L mutation alone does not mean that HPAI H5N1 is about to cause a widespread pandemic. Other genetic mutations would likely be required for the virus to spread between people. In the context of an increasing number of human H5N1 cases resulting from direct contact with infected animals, the findings highlight the importance of continued efforts to control outbreaks and continued genomic surveillance to monitor the emergence of HPAI H5N1 genetic changes and maintain public health preparedness.
The research was funded in part by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), through its Centers of Excellence for Influenza Research and Response program.