Single mutation in H5N1 flu surface protein could facilitate human infection

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A single change in the protein on the surface of the highly pathogenic avian influenza (HPAI) virus H5N1, which is currently circulating among U.S. dairy cows, could make it easier for humans to contract the disease, according to a new study funded by the National Institutes of Health and published in the journal Animal Health today. Scientists are able to explain the origins of scienceThe study results reinforce the importance of continued surveillance and monitoring of HPAI H5N1 to detect any genetic changes that could increase viral transmission in humans.

Current strains of the bovine H5N1 virus are not transmissible to humans. However, people who have been exposed to wild birds, chickens, dairy cows, and other mammalian species infected with the virus can become infected. Researchers have been monitoring the H5N1 strain for many years as part of their pandemic preparedness efforts to better understand how viral mutations occur naturally and whether they impact transmission.

The influenza virus attaches to the surface of cells with a viral protein called hemagglutinin. To cause infection, hemagglutinin attaches to receptors for sugar molecules (glycans) on cells. Avian influenza viruses, such as H5N1, have not been able to infect humans because the human upper respiratory tract lacks the cellular receptors that birds have. Scientists are concerned that the virus could evolve to recognize the human-like receptors in the upper respiratory tract, allowing it to spread and infect humans.

Scripps Research scientists used the H5N1 isolate from the first human infection in the United States with the bovine strain (2.3.4.4b) A/Texas/37/2024 to determine how changes in the HA gene sequence affected the protein’s binding to human receptors. The researchers introduced mutations into viral HA proteins that have been observed in nature and found that Q226L improved the protein’s ability to bind to receptors typically found on human cells. The researchers did not use viruses to conduct their experiments or create the mutations. They only introduced genetic changes to the surface of the HA protein.

According to the authors, experimental results obtained with Q226L alone do not indicate that HPAI H5N1 virus will cause a pandemic. It is likely that other genetic mutations are required to spread the virus among humans. These results, in the context of an increasing number of human cases of H5N1 resulting from contact with animals infected with the virus, underscore the need for continued epidemic control efforts and genomic surveillance. This will allow us to genetically track any changes in HPAI H5N1 virus and ensure public health preparedness.

The Centers of Excellence for Influenza Research and Response program at the National Institute of Allergy and Infectious Diseases of the NIH funded part of this research.

The article below provides more information about the item.

TH Lin The et all. A mutation in the hemagglutinin of bovine influenza H5N1 alters its specificity for human receptors. Scientists are able to explain the origins of science DOI: 10.1126/science.adt0180 (2024).

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NIAID Director Jeanne Marrazzo, MD, and Erik Stemmy, Ph.D., program officer in the Respiratory Diseases Branch of NIAID's Division of Microbiology and Infectious Diseases, are available to comment on these findings.

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