H5N1 virus isolated from infected dairy worker is 100% lethal in ferrets, but does not appear to be circulating in nature anymore

The good news: the dairy worker experienced mild symptoms and fully recovered, and the H5N1 strain that infected the worker does not appear to have continued spreading in the wild.

Still, the findings highlight the risks posed by a virus that continues to spread among dairy cattle and occasionally to farm workers, and the study's lead scientist says he was surprised by the ease with which this particular strain was able to kill ferrets.

"This is one of the most pathogenic viruses I've ever seen in ferrets," says Yoshihiro Kawaoka, a UW-Madison professor of pathobiological sciences who spearheaded the work, described Oct. 28, 2024, in the journal Nature.

Ferrets are a common model for studying how influenza viruses that primarily affect birds are able to adapt to mammals, a topic that Kawaoka and his colleagues at UW-Madison's Influenza Research Institute investigate since such a jump could trigger an influenza pandemic.

Like other influenza viruses, H5N1 viruses mutate at a relatively rapid clip as they infect new hosts. Sometimes these mutations allow the viruses to more easily infect and spread among new species. That's how the current viruses, which have been infecting birds around the world in recent years, began to spread among mammals, most notably North American dairy cattle in 2024.

Kawaoka and his collaborators found that the H5N1 virus that infected the Texas dairy worker included a mutation that the team first identified in 2001 as important for causing severe disease. Luckily, Kawaoka says, the strain with that mutation seems to have died out.

"This isolate is unique among the H5N1 viruses circulating in cows," he says.

Kawaoka hypothesizes that H5N1 viruses took two paths when they made the jump from birds to cows, both facilitated by mutations that made the virus better adapted to mammals.

Kawaoka and his colleagues suggest that one path resulted in the more concerning mutation found in the Texas dairy worker, while the other led to a less dangerous mutation in the same protein.

"Both mutations give the virus the ability to adapt to mammals, but the good thing is the one containing this more pathogenic mutation has not been detected again," Kawaoka says. "So there are no extremely pathogenic H5N1 viruses currently circulating in cows. However, if a currently circulating cow H5N1 virus acquires that mutation, then that would be an issue."

Whether a virus with such a mutation would be dangerous for humans remains to be seen.

"The puzzling thing is why the human who got this virus did not have a severe infection," says Kawaoka, noting a few possibilities.

Perhaps exposure to seasonal influenza viruses provides some level of protection via antibodies, or maybe the route of infection is important; the Texas dairy worker's main symptom was conjunctivitis, suggesting the virus entered through the eye rather than the more typical respiratory route.

Alternatively, more robust surveillance of influenza cases among American dairy workers since the virus began spreading on farms might mean more cases -- including mild ones -- are being identified. Another possibility is this particular strain might simply be less severe in humans than mammals like ferrets.

"Those are all possibilities, but we don't know," says Kawaoka. "So, we're now trying to understand why this virus is so pathogenic in ferrets and what that could mean for human infections."