Highly pathogenic H5N1 avian influenza was discovered in dairy cattle in the United States for the first time in March, and by May, nine states had reported outbreaks. The way the virus spreads among cattle is currently not known, but recent studies indicate that a related strain of H5N1, known as subtype clade 2.3.4.4b, which caused an outbreak in farmed mink in 2022, was able to spread through the air to a small number of ferrets. This is the first instance of a virus from the H5N1 clade 2.3.4.4b group demonstrating this capability. According to the researchers, these findings suggest that these viruses are evolving to infect mammals.
The highly dangerous H5N1 avian influenza virus was found in dairy cattle in the United States for the first time in March, and by May, nine states had reported outbreaks. While it is currently unknown how the virus spreads among cattle, a new study published in Nature Communications on May 15 shows that a similar strain of H5N1, known as subtype clade 2.3.4.4b, which caused an outbreak in farmed mink in 2022, was able to spread through the air to a limited number of ferrets. This is the first time that a virus from the H5N1 clade 2.3.4.4b group has been shown to have an increased risk of transmission among humans.The ability to evolve to infect mammals with a potentially increased risk to humans is exhibited by these viruses, according to the study led by Penn State researchers. ”While there is no evidence that the strain of H5N1 currently affecting dairy cattle is capable of airborne transmission, our study suggests that another member of this virus family has evolved some degree of airborne transmissibility,” said Troy Sutton, associate professor of veterinary and biomedical sciences at Penn State and the paper’s corresponding author. The researchers emphasized the importance of continued monitoring to track the development of these viruses and their spread to other animals, including humans.”
Evaluating a virus’s ability to spread through the air in mammals could provide insight into its potential threat to humans, the researchers stated. Because virus samples were not easily accessible after the mink outbreak was contained, the team reconstructed the virus using genetic sequences that were publicly available.
The researchers then tested the virus’s ability to spread in ferrets, which have respiratory systems that are more comparable to humans in terms of susceptibility to viral infections.The researchers conducted a study on ferrets to understand how the flu virus is transmitted. They found that ferrets are a more suitable model for studying flu transmission compared to mice. The team measured the transmission of the virus through direct contact and through airborne transmission. They also assessed the severity of the disease by monitoring the ferrets’ weight loss and clinical signs of illness.
The results showed that the virus was transmitted to 75% of exposed ferrets through direct contact and to 37.5% through respiratory droplets after about nine days of exposure. The study highlights the importance of understanding how the flu virus spreads in order to develop effective prevention and control measures.The virus had a small infectious dose and even a small amount of virus could cause an infection. Sutton discovered that the mink strain of the virus had a mutation called PB2 T271A. When the team removed this mutation from the engineered virus, they found that the mortality and airborne transmission in infected ferrets was reduced. Sutton concluded that the PB2 T271A mutation enhances viral replication, which contributes to the virulence and transmission of the virus in ferrets. Understanding the role of this mutation is crucial in controlling the virus.This genetic mutation allows us to keep an eye out for it or similar mutations that may appear in the currently circulating strains of H5N1. Sutton also noted that the ferrets used in the team’s studies had no previous immunity to influenza, unlike most humans who have been exposed to H1N1 and H3N2 seasonal influenza viruses. He mentioned that this exposure would probably provide some level of protection against H5N1 if humans come into contact with another H5N1 variant. Additionally, he stated that the transmission rate observed in the mink virus is lower than what is typical for pandemic influenza.According to Sutton, pandemic influenza viruses usually spread to 75% to 100% of contacts through the air in three to five days, but the mink virus we studied only spread to less than 40% of contacts after nine days,” Sutton said. “Our studies show that the mink virus has a higher potential for causing a pandemic compared to previously known strains of H5N1, but it does not share the same characteristics as pandemic strains. The H5N1 strain affecting cattle has also not caused severe illness in cattle or humans, but the longer the virus persists and the more exposure humans have to it, the greater the risk.The study was carried out at the Eva J. Pell Advanced Biological Laboratory at Penn State, a high-containment biosafety level 3 enhanced laboratory that undergoes regular inspections by the Centers for Disease Control and Prevention and the United States Department of Agriculture. Other Penn State contributors to the paper include Katherine Restori, who is an assistant research professor in veterinary and biomedical sciences, along with graduate students Kayla Septer, Cassandra Field, and Devanshi Patel. David VanInsberghe, a postdoctoral fellow, and Vedhika Raghu also contributed to the research.Nathan, a graduate student, and Anice Lowen, a professor of microbiology and immunology, both at Emory University, are also contributing authors of the paper.
This research was supported by the National Institutes of Health and the National Institute of Food and Agriculture.