NIH: Mutation in Avian Influenza Protein Could Enable Easier Human Infection, But Risk of Infection Remains Low
Jeanne Marrazzo, MD, MPH, director of NIAID, discusses the mutation changes needed to make human-to-human transmission easier as well as infection prevention strategies.
Influenza A (H5N1/bird flu) virus particles (rod-shaped). Layout incorporates 2 CDC transmission electron micrographs that have been inverted and creatively repositioned and colorized by NIAID. Scales have been modified.
Image Credit: CDC and NIAID
There continues to be a smattering of H5N1 (avian influenza) cases being reported around the United States. As of December 6, 2024, the Centers for Disease Control and Prevention (CDC) reports there are 58 confirmed cases of H5N1 in the country. 1
In a majority of the cases, the infections are occurring in individuals who are working on farms and have contact with cows. Most recently, 2 more dairy workers in California were confirmed to have the virus. The state has the largest number of cases in the nation with 32.1
Related to avian influenza and cows, a new National Institutes of Health (NIH)-funded study shows a single modification in the protein found on the surface of the H5N1 virus currently circulating in dairy cows in the US could allow for easier transmission among humans.2-3
The study was published in the journal Science.
Investigators at Scripps Research isolated the first US human H5N1 infection with the 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 avian 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 ability of the protein to attach to receptors typically 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 conduct experiments with a whole, infectious virus. 2
The experimental finding with the Q226L mutation alone does not mean HPAI H5N1 is on the verge of causing a widespread pandemic, the authors note. Other genetic mutations would likely be required for the virus to transmit among people. In the setting of a growing number of H5N1 human cases resulting from direct contact with infected animals, the findings stress the importance of continued efforts at outbreak control and continued genomic surveillance to monitor for the emergence of HPAI H5N1 genetic changes and maintain public health preparedness. 2
Current strains of the bovine (cow) H5N1 virus are not known to be transmissible among people, but infections have occurred in people exposed to infected wild birds, poultry, dairy cows, and other mammals. Avian influenza viruses have not infected people frequently because the human upper respiratory tract lacks the avian-type cell receptors found in birds. However, the science community is concerned that viruses could mutate to recognize human-type cell receptors in the upper airways and acquire the ability to infect people and transmit from human-to-human.2
Jeanne Marrazzo, MD, MPH, director of the NIAID
Image Credit: NIAID
Contagion posed some questions to NIH’s National Institute of Allergy and Infectious Diseases (NIAID) Director Jeanne Marrazzo, MD, MPH, on this topic including the NIH’s mutation study, the risk of consuming raw milk, and preventative measures for the public to consider when coming into contact with wild animals.
Contagion: Can you talk about the surveillance measures to monitor changes to H5N1. And if it does mutate, when will the public be made aware of this development?
Marrazzo: A number of different academic and government networks are currently conducting H5N1 genomic surveillance efforts. For example, the Centers of Excellence for Influenza Research and Response (CEIRR) network, which is supported by NIAID, supported the research outlined in this paper. Investigators in the CEIRR network also study H5N1 in wild birds and in domesticated animals, such as dairy cattle, to learn about its evolution as it spreads in animals.
Government agencies are also conducting H5N1 surveillance. For instance, the Centers for Disease Control and Prevention (CDC) conducts extensive human influenza monitoring activities, and makes regular public announcements when new varieties of influenza or epidemiologically significant mutations are identified. The US Department of Agriculture similarly conducts surveillance on influenza isolates from animals such as dairy cows and poultry.
Contagion: What is the likelihood of the mutation happening that could enable easier human infection?
Marrazzo: It is difficult to predict the likelihood that the particular mutation described in this study will occur—and, moreover, the virus would still likely need to acquire additional mutations to acquire the ability to spread effectively among humans.
In addition, the study assessed only the effect of the mutation on hemagglutinin protein binding and not the whole virus, thus the effect of the mutation on viral replication, stability, and other characteristics is unknown. The findings of this study highlight the need for continued vigilance and continued need to prioritize control of spread among animals.
Contagion: What can people do to prevent contracting avian influenza?
Marrazzo: The CDC recommends avoiding direct contact with wild birds or other wild animals, especially if they appear to be sick or dead. Wild birds can also be infected with H5N1 and not appear sick, so it is better to observe them from a distance. People who live and work alongside domesticated animals which may be potentially infected, such as poultry or dairy cattle, can take extra precautions to avoid contact with infected animals and their contaminated environments. For example, wearing personal protective equipment can help dairy farm workers reduce exposure to infectious milk.
While there are no documented cases of humans directly catching H5N1 influenza from drinking raw unpasteurized milk, raw milk produced by cattle infected with H5N1 contains high levels of the virus. Fortunately, pasteurization appears to kill the flu virus. Because of the risk of exposure to the H5N1 flu virus, as well as other harmful diseases, people should not consume raw milk or products, such as fresh cheese, that are made with raw milk.
