H5N1 Strain Shows Limited Airborne Transmission in Ferrets

The highly virulent H5N1 avian influenza was initially found in dairy cattle in the United States in March, and by May, outbreaks had been reported from nine states. The research was published in the journal Nature Communications.

Research shows that a related strain of H5N1, subtype clade 2.3.4.4b, which caused an outbreak in farmed mink in 2022, spread by air to a small number of ferrets, even though the method of transmission among cattle is currently unknown.

This is the first instance of this ability being demonstrated in a member of the H5N1 clade 2.3.4.4b virus group. The research principal investigators from Penn State explained that these viruses are evolving to infect mammals and may pose a greater risk to humans.

While there is no evidence that the strain of H5N1 that is presently affecting dairy cattle is capable of airborne transmission, our study suggests that another member of this family of viruses has evolved some degree of airborne transmissibility, this finding underscores the importance of continued surveillance to monitor the evolution of these viruses and their spillover into other mammals, including humans.”

Troy Sutton, Associate Professor and Study Corresponding Author, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University

The researchers claim that determining a virus's potential risk to humans may be aided by evaluating its capacity for airborne transmission in mammals. After the mink outbreak was contained, the team used genetic sequences that were freely available to recreate the virus because it was difficult to collect virus samples.

The researchers then assessed the virus's potential to spread in ferrets, whose respiratory systems are more akin to those of humans than other model creatures like mice in terms of their vulnerability to viral infection and transmission. 

They evaluated the virus's spread indirectly through the air by putting infected and uninfected ferrets in cages that allowed for shared airspace but forbade physical contact and directly by sticking infected ferrets in cages with uninfected ferrets. The group looked at the ferrets' weight loss and any indications of a clinical illness to gauge the severity of the condition.

After approximately nine days of exposure, the researchers discovered that the virus was spread to 37.5% of exposed ferrets via respiratory droplets and by direct contact to 75% of exposed ferrets. The researchers also discovered that even minute quantities of the virus might cause infection due to its low infectious dosage.

Sutton reported that the virus's mink strain has a mutation known as PB2 T271A. The researchers created a version of the virus without the mutation to examine its impact on viral transmission and disease severity. They discovered that the infected ferrets had lower mortality and airborne transmission rates. 

These findings suggest that the PB2 T271A mutation is enhancing viral replication of the virus, contributing to both virulence and transmission in ferrets, understanding the role that this mutation plays means we can monitor for it or for similar mutations to arise in the currently circulating strains of H5N1.”

 Troy Sutton, Associate Professor and Study Corresponding Author, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University 

Sutton noted that while most people have been exposed to the H1N1 and H3N2 seasonal influenza viruses, the ferrets the team utilized in their studies did not have a preexisting immunity to influenza. 

Sutton said, “This exposure would likely offer some degree of cross-protection against H5N1 if humans are exposed to another H5N1 variant.”

Moreover, he indicated that the transmission rate observed in the mink virus by the team is lower than what is typical for pandemic influenza viruses.

Sutton added, “Pandemic influenza viruses typically transmit via the airborne route to 75% to 100% of contacts within three to five days, whereas the mink virus we studied transmitted to fewer than 40% of contacts after nine days.” 

The transmission observed in our studies is indicative of increased pandemic potential relative to previously characterized strains of H5N1; However, the mink virus does not exhibit the same attributes as pandemic strains. The H5N1 strain affecting cattle also has not caused severe disease in cattle or humans, but the longer the virus circulates, and the more exposure humans have to it, the greater the chances that it will evolve to infect humans.”

 Troy Sutton, Associate Professor and Study Corresponding Author, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University