Human H5N1 Bird Flu More Virulent in Mice Than Bovine Strain

Researchers from the Texas Biomedical Research Institute reported that one of the first strains of bird flu to be isolated from a human in Texas exhibits a distinct set of mutations that allow it to more readily replicate in human cells and inflict more severe disease in mice than a strain found in dairy cattle.

The discovery draws attention to a serious issue with the H5N1 bird flu strains currently circulating in the United States and raises questions about how quickly the virus can change when exposed to a new host.

H5N1, which is naturally present in wild birds and deadly in chickens, has spread to many different mammals and, in the spring of 2024, started to infect dairy cows. By early 2025, the outbreak had infected dozens of people, primarily farm workers, and had spread through herds in several US states.

The virus does not spread from person to person, and the majority of infected individuals only have mild illness and eye inflammation. After being exposed to infected chickens, the first H5N1 death in the United States was documented in January 2025.

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.”

Luis Martinez-Sobrido, Professor, PhD, Texas Biomedical Research Institute

Sobrido’s influenza virus research lab has been researching H5N1 since the outbreak started last year. To test preventative vaccines and therapeutic antivirals, the team has created specialized instruments and animal models.

Human vs. Bovine

The H5N1 strains isolated from dairy cattle in Texas and a human patient were compared in the most recent study.

“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 studies on mice, they discovered that the human strain was much more prevalent in brain tissue, replicated more effectively, and caused more severe disease than the bovine strain. Additionally, they examined the effectiveness of many FDA-approved antiviral drugs against both virus strains in cells.

Fortunately, the mutations did not affect the susceptibility to FDA-approved antivirals.”

 Ahmed Mostafa Elsayed, Staff Scientist and Study First Author, Texas Biomedical Research Institute

If a pandemic breaks out before vaccines are generally accessible, antivirals will be a crucial line of defense, according to Dr. Martinez-Sobrido. According to a separate study carried out in cooperation with Aitor Nogales, PhD, at the Center for Animal Health Research in Spain, this is particularly true since humans do not have any innate immunity against H5N1, and seasonal flu vaccinations seem to provide very little protection.

Next Steps and Recommendations

To find out which human H5N1 mutations are causing the increased pathogenicity and virulence, Texas Biomed is currently investigating each one separately. The team is trying to determine why H5N1 can infect such a large number of mammal species, why it causes mild illness in cows but kills cats, and why infections from cows are less dangerous to humans than those from chickens.

In a third paper for the journal mBio, Dr. Elsayed and associates examined the history of H5N1 in dairy cattle and advocated for a One Health strategy to safeguard humans and animals.

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. 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.”

Ahmed Mostafa Elsayed, Staff Scientist and Study First Author, Texas Biomedical Research Institute