Dairy cattle H5N1 virus remains adapted to birds, with little sign of human spread

Avian influenza virus from the ongoing outbreak in dairy cattle appears to be keeping its bird-infecting features rather than adapting to better infect other mammals, according to a new study from St. Jude Children’s Research Hospital. Since 2024, when scientists first detected H5N1 bird flu in dairy cattle, they have worried that the virus would use the animals as a bridge to mutate and gain the ability to better infect and spread in humans.

The St. Jude researchers tested a panel of these viruses from dairy cows, finding they had more molecular and biological features in common with avian than human flu viruses. In addition, the viruses from cows could not transmit through the air between mammals, though direct infection of an individual human from close contact with infected dairy cattle is possible. The findings were published recently in Nature Communications.

“We found that these flu viruses from cow udders are not under a lot of pressure to mutate to better infect other mammals such as humans,” said corresponding author Richard Webby, Ph.D., St. Jude Department of Host-Microbe Interactions. “For now, the risk of becoming a pandemic threat to humans appears low, though the risk of direct infection for those working with these animal remains high.”

The scientists compared five flu viruses sampled from dairy cows to the closest related strains found in birds and humans. In almost all cases, the bovine viruses more closely resembled the avian influenza strains. The viral proteins from the cow and bird flu strains had the most similar genetic sequences and bound to receptors on avian cells far more efficiently than to receptors found on mammalian cells. Those features indicate that the virus is unlikely to spread well in humans in its current form.

Assessing bovine influenza virus’s risk to humans

While they may not infect humans efficiently, these viruses from dairy cows have already caused at least 41 infections in people through close contact with dairy cattle. The scientists therefore wanted to know if the viruses could spread between humans, so they studied a mammalian model of human influenza infection.

The models could not pass the bovine flu to each other through the air. However, these models could spread the virus through direct contact. The lack of airborne transmission indicates a low risk of spreading between humans, but the other experiments suggest that there is still a threat of direct infection. Therefore, the scientists looked to see if current interventions for flu could help treat such infections.

They started by examining the immune molecules in the blood of people vaccinated against avian influenza. “We found that when we tested sera from patients in a clinical trial for this flu vaccine for a different strain, they had some cross-protection against these bovine viruses,” said first author Tom Fabrizio, Ph.D., St. Jude Department of Host-Microbe Interactions.

If vaccines fail, then physicians will reach for antivirals to treat an infected individual. There are two antivirals used in patients with influenza, so the researchers measured how well both controlled H5N1 infections from the cow viruses in the lab and studied genetic markers of treatment resistance.

“Our results predict that these antivirals should work effectively against these viruses,” Fabrizio said. “We also saw no indication that they’re gaining any ability to resist these drugs.”

While the results are encouraging, they do not mean that these bovine viruses are innocuous. Infected mammalian models still showed many signs of sickness, as have some humans. In addition, the virus continues to evolve, so these results may not apply in the future if a new variant arises.

“Right now, these bovine flu viruses pose a threat at the individual level, specifically to those working closely with infected animals or drinking raw infected milk, rather than the population level,” Webby said. “But we need to remain vigilant for human infections, as each new person infected is another chance for this virus to mutate to better infect and spread among us.”