A human strain of H5N1 bird flu isolated in Texas shows mutations enabling better replication in human cells and causing more severe disease in mice compared to a bovine strain. While the virus isn’t yet spreading between humans, experts warn of its potential to evolve and stress the need for antiviral preparedness and improved animal control measures.

Researchers at the Texas Biomedical Research Institute (Texas Biomed) have identified a strain of bird flu isolated from a human in Texas that carries a distinctive set of mutations, making it more adept at replicating in human cells and causing severe disease in mice. This strain was compared to one found in dairy cattle, and the findings are detailed in Emerging Microbes & Infections.

The discovery underscores a significant concern about the H5N1 strains of bird flu currently circulating in the U.S.: the virus’s rapid mutation when it infects a new host species.

H5N1, which is naturally present in wild birds and deadly to chickens, has recently spread to a wide range of mammals and, for the first time in the spring of 2024, began infecting dairy cows.

As of early 2025, the outbreak had spread through herds across multiple states in the U.S. and infected dozens of people, mostly farm workers. So far, most people infected experience mild illness and eye inflammation and the virus is not spreading between people. The first H5N1 death in the U.S. was reported in January 2025 following exposure to infected chickens.

Professor Luis Martinez-Sobrido, Ph.D., (left) and Staff Scientist Ahmed Mostafa Elsayed, Ph.D., (right) review test results for the presence of bird flu while wearing protective equipment required for biosafety level-3 laboratories. Credit: Texas Biomed

“The clock is ticking for the virus to evolve to more easily infect and potentially transmit from human to human, which would be a concern,” said Texas Biomed Professor Luis Martinez-Sobrido, Ph.D., whose lab specializes in influenza viruses and has been studying H5N1 since the outbreak began last year. The team has developed specialized tools and animal models to test prophylactic vaccines and therapeutic antivirals.

Human vs. bovine

In the recent study, they compared H5N1 strains isolated from a human patient and from dairy cattle in Texas.

“There are nine mutations in the human strain that were not present in the bovine strain, which suggests they occurred after human infection,” Dr. Martinez-Sobrido said.

In mouse studies, they found that compared to the bovine strain, the human strain replicated more efficiently, caused more severe disease, and was found in much higher quantities in brain tissue. They also tested several FDA-approved antiviral medications to see if they were effective against both virus strains in cells.

“Fortunately, the mutations did not affect the susceptibility to FDA-approved antivirals,” said Staff Scientist Ahmed Mostafa Elsayed, Ph.D., first author of the study.

Antivirals will be a key line of defense should a pandemic occur before vaccines are widely available, Dr. Martinez-Sobrido said. This is especially true since humans have no preexisting immunity against H5N1 and seasonal flu vaccines appear to offer very limited protection, according to a separate study conducted in collaboration with Aitor Nogales, Ph.D., at the Center for Animal Health Research in Spain.

Next steps and recommendations

Texas Biomed is now exploring the human H5N1 mutations individually to determine which are responsible for increased pathogenicity and virulence. The team wants to figure out what allows H5N1 to infect such a wide range of mammal species; why H5N1 causes mild disease in cows but is lethal in cats; and why infections via cows are less harmful to people than infections from chickens.

In a third paper, Dr. Elsayed and collaborators analyzed the history of H5N1 in dairy cattle for the journal mBio and called for a One Health approach to protect both animals and people.

“A key priority will be to eradicate bird flu from dairy cows to minimize the risk of mutations and transmission to people and other species,” Dr. Elsayed said. “Steps that can be taken now include thorough decontamination of milking equipment and more stringent quarantine requirements, which will help eliminate the virus more quickly in cows.”

References:

“Replication kinetics, pathogenicity and virus-induced cellular responses of cattle-origin influenza A(H5N1) isolates from Texas, United States” by Ahmed Mostafa, Ramya S. Barre, Anna Allué-Guardia, Ruby A. Escobedo, Vinay Shivanna, Hussin Rothan, Esteban M. Castro, Yao Ma, Anastasija Cupic, Nathaniel Jackson, Mahmoud Bayoumi, Jordi B. Torrelles, Chengjin Ye, Adolfo García-Sastre and Luis Martinez-Sobrido, 8 January 2025, Emerging Microbes & Infections.
DOI: 10.1080/22221751.2024.2447614

“Avian influenza A (H5N1) virus in dairy cattle: origin, evolution, and cross-species transmission” by Ahmed Mostafa, Mahmoud M. Naguib, Aitor Nogales, Ramya S. Barre, James P. Stewart, Adolfo García-Sastre and Luis Martinez-Sobrido, 13 November 2024, mBio.
DOI: 10.1128/mbio.02542-24

“Are we serologically prepared against an avian influenza pandemic and could seasonal flu vaccines help us?” by Iván Sanz-Muñoz, Javier Sánchez-Martínez, Carla Rodríguez-Crespo, Corina S. Concha-Santos, Marta Hernández, Silvia Rojo-Rello, Marta Domínguez-Gil, Ahmed Mostafa, Luis Martinez-Sobrido, Jose M. Eiros and Aitor Nogales, 31 December 2024, mBio.
DOI: 10.1128/mbio.03721-24

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