A strain of H5N1 avian influenza virus found in a Texas dairy worker who was infected this spring was able to spread among ferrets through the air, although inefficiently, and killed 100% of infected animals in studies University of Wisconsin-Madison researchers performed with the strain earlier this year.
The good news: the dairy worker experienced only experienced mild inflammation of the cornea (conjunctivitis) 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, published this week 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.”
RESEARCH DETAILS
The virus isolated from the worker is called huTX37-H5N1 and has a mutation (PB2-E627K) frequently seen in avian influenza viruses that replicate in mammals, typically making virus replication more efficient. These mutations underscore the need for continued monitoring and evaluation of viruses from the current H5N1 outbreak.
The study also showed that a bovine H5N1 virus is susceptible to the antiviral drugs favipiravir and baloxavir marboxil (brand name Xofluza) of the polymerase inhibitor class, as well as the neuraminidase inhibitor zanamivir. The virus is less sensitive to oseltamivir (Tamiflu), another neuraminidase inhibitor.
In laboratory experiments, huTX37-H5N1 replicated in human cornea and lung cells. The scientists determined the lethal dose of huTX37-H5N1 as less than 1 plaque-forming unit (PFU) in mice, compared to 31.6 PFU as the lethal dose of a bovine H5N1 virus isolated from the milk of a lactating cow. The huTX37-H5N1 virus also infected each of 15 different mouse tissues tested, with the highest virus levels found in respiratory tissues.
Researchers also infected ferrets with a high dose of huTX37-H5N1. Flu infections in ferrets more closely resemble human flu infections than those in mice. All infected ferrets died within 5 days and scientists found huTX37-H5N1 virus in all the tissues sampled, with high levels in the respiratory system. In a prior study, the researchers had infected ferrets with a bovine H5N1 virus and, although it caused severe disease, lethality was limited.
To evaluate respiratory transmission, the scientists placed healthy ferrets in cages about 5 centimeters away from ferrets infected one day earlier with one of four decreasing doses of huTX37-H5N1. All directly infected ferrets died within 6 days and, depending on the exposure dose, between 17 percent and 33 percent of the nearby animals became infected via respiratory droplet transmission. These results indicate that a bovine HPAI H5 virus isolated from an infected person can transmit among mammals via respiratory droplets, though with limited efficiency.
Scientists from the University of Wisconsin at Madison led the research with collaborators from Shizuoka and Tokyo Universities and the Research Center for Global Viral Diseases in Japan. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, funded much of the work through its Centers of Excellence for Influenza Research and Response program.
READ MORE
- A human isolate of bovine H5N1 is transmissible and lethal in animal models. Nature
- The current situation with H5N1 avian influenza and the risk to humans. Internal Medicine Journal
- Pre-existing H1N1 immunity reduces severe disease with bovine H5N1 influenza virus. BioRxiv pre-print
- Environmental stability of HPAIV H5N1 in raw milk, wastewater and on surfaces. BioRxiv pre-print
Sources: National Institute of Allergy and Infectious Diseases, University of Wisconsin-Madison, Nature