The ongoing outbreak of avian influenza, which began in late 2021 in Europe and the Americas, has been marked by rapid genetic changes and highly increased virulence in both birds and mammals, according to a new study published last week.
In the peer-reviewed study published in Nature Communications, researchers from the St. Jude Children’s Research Hospital in Memphis, Tennessee, found that the new strains of the H5N1 avian influenza virus changed rapidly and became more severe as they spread through Europe and the Americas in the past two years.
In recent months, increasing numbers of mammals have been found to be infected with the virus, with mass die-offs of seals and sea lions reported in Russia and the Americas and dozens of foxes, skunks, dolphins, raccoons, cats and other mammals found to be infected as well.
“We haven’t seen a virus quite like this one,” said corresponding author Richard Webby of St. Jude's Department of Infectious Diseases in a press release. “In 24 years of tracing this particular H5N1 flu lineage, we haven’t seen this ability to cause disease but also be maintained in these wild bird populations.”
The scientists found that the virus gained a different version of a viral protein called neuraminidase, which increased its ability to transmit between birds, before arriving in Canada and then spreading to the rest of the Americas.
After reaching Canada, the virus quickly mutated again, mixing with other flu viruses and becoming more adapted to the bird population, including species that used to not be as affected by the flu.
The virus also became more severe since it spread to the Americas, with ferrets infected with samples of the virus collected from an infected eagle in February 2022 experiencing rapid weight loss, lethargy and severe neurologic symptoms such as paralysis and impaired muscle control.
“Some of these are really nasty viruses,” added Webby. “There’s a huge amount of the virus in the brain of infected animals. That’s the hallmark of what we saw with these flu strains — increased pathogenicity associated with high virus load in the brain. That’s not the first time we’ve seen H5 viruses in the brain, but these are probably some of the most virulent we’ve looked at over 24 years of following these viruses.”
The researchers also infected ferrets with samples of the virus collected later in the outbreak. The researchers noted that the virus samples with more gene segments acquired from North American lineages seemed to cause more severe disease.
Webby stressed that this situation is surprising as the viruses' ability to cause severe disease changed with just a few reassosrtment events.
Avian influenza remains 'low-risk' to humans, but is evolving
The scientists stressed that while the increased pathogenicity of the virus is "of significant concern," the virus still has not adapted to spread efficiently between humans and is still low-risk to humans. The scientists did, however, note that only a few amino acid changes in a few flu proteins are needed in order to enable sustained human-to-human transmission.
“Overall, their risk to humans is still low,” said Webby. “But that risk does seem to be changing, and these viruses are doing things that we haven’t seen H5s do before. They’ve come into the continent’s wild bird population, they’ve reassorted, and they’ve been maintained over time. There are now many different types out there, and they're very nasty.”
In a recent interview with AFP, Ian Brown, virology head at the UK's Animal and Plant Health Agency, stated that it would take "two or three minor changes in one protein of the viruses" for the bird flu to become more adapted to humans.
'Largest-ever' outbreak of bird flu continues to hit Europe, Americas
Since 2021, Europe and the Americas have been suffering from a continuous outbreak of H5N1 avian influenza which has been described as "the largest-ever" outbreak on both continents.
The outbreak has been widely affecting both birds and mammals. In the US alone, over 58 million poultry have been affected and thousands of infected wild birds have been found in almost every state. Nearly 200 cases have been detected in mammals across the US as well. In Europe, tens of thousands of wild and domestic birds were found to be infected in over 24 countries, with many sea birds affected.
Human cases have been detected in the UK, US, Cambodia, Ecuador and Chile.
In May, Canadian authorities detected the H5N5 subtype of avian influenza in a raccoon on Prince Edward Island, marking the first time the strain has ever been detected in a mammal.
In April, a pre-print study by Canadian researchers found that a strain of H5N1 isolated from a red-tailed hawk was able to effectively transmit between ferrets, causing deadly illness in the mammals.
The researchers in that study noted that the virus sample isolated from the red-tailed hawk contained signs of adaptation to mammals, suggesting that the hawk may have been infected by eating mammalian carrion. Its passage through multiple species may have contributed to its enhanced transmissibility in ferrets as well.
Ferrets are seen as an important animal model for analyzing how viruses could affect humans as they can be infected by human influenza viruses and exhibit similar symptoms to humans.
In past studies, H5N1 has usually not been transmitted efficiently between ferrets, although it has been shown to sometimes cause lethal illness.