A new strain of bird flu that transmits easily among wild birds has triggered an explosive spread into new corners of the globe, infecting and killing a variety of mammals species and raising fears of a pandemic more lethal than COVID-19.
But the very changes that have allowed the virus to infect wild birds so efficiently likely made it harder to infect human cells, leading disease experts told Reuters. Their views underpin global health officials’ assessments that the current outbreak of H5N1 poses low risk to people.
The new strain, called H5N1 clade 2.3.4.4b, emerged in 2020 and has spread to many parts of Africa, Asia and Europe as well as North and South America, causing unprecedented numbers of deaths among wild birds and domestic poultry.
The virus has also infected mammals ranging from foxes and grizzly bears to seals and sea lions, likely from feeding on diseased birds.
Unlike earlier outbreaks, this subtype of H5N1 is not causing significant disease in people. So far, only about a half dozen cases have been reported to the World Health Organization (WHO) in people who had close contact with infected birds, and most of those have been mild.
“We think the risk to the public is low,” Dr. Timothy Uyeki, chief medical officer of the U.S. Center for Disease Control and Prevention’s (CDC) Influenza Division, said in an interview. The WHO expressed a similar view in an assessment earlier this month.
The way this virus enters and infects cells is one reason for the muted concern, flu experts told Reuters. They say the attributes that have made this virus thrive in wild birds likely make it less infectious to people.
“It’s clear that this is a very, very successful virus for birds, and that almost excludes it from being a very, very successful virus in mammals,” said Richard Webby, director of the WHO Collaborating Center for Studies on the Ecology of Influenza in Animals and Birds at St. Jude Children’s Hospital.
Experts see the spillover into mammals as an early warning sign to step up virus surveillance rather than a signal of a new pandemic.
“Everybody take a breath,” Dr. Michael Osterholm, an infectious disease expert at the University of Minnesota who has tracked H5N1 since it first emerged in 1997, said of those sounding alarm bells.
WHAT ABOUT THE MINKS?
What raised concern among virologists was a study published in January in the medical journal Eurosurveillance showing potential mammal-to-mammal transmission of the virus on a mink farm in Spain.
“It is highly plausible that a virus capable of mink-to-mink transmission is capable of human-to-human transmission,” Michelle Wille, an expert in the dynamics of wild bird viruses at the University of Sydney, said in an email.
That is a scenario that disease experts have been warning about for decades. Mink share many attributes with ferrets, an animal often used in flu experiments because of their similarity to humans.
Although the exact changes required for a bird flu virus to become easily transmissible in people are not known, a pair of landmark studies done a decade ago offer some clues.
Using so-called gain of function experiments, scientists intentionally altered the H5N1 virus to make it transmissible in ferrets and found that as few as five highly specific mutations were required.
Most of the mammalian cases so far have had only one of these mutations – in a gene called PB2 – which was present in the mink. Webby said the virus can make that change easily.
What has not changed, even in mink, is that the virus still prefers to bind to avian-type receptors to enter and infect cells. Mink have both avian and human-type receptors, but avian receptors are scarce in humans and located deep in the lungs.
Human flu viruses typically bind to receptors found in the upper respiratory tract.
“We know that avian viruses can occasionally affect people, but it takes what appears to be lots and lots of contact with birds,” said James Lowe, a professor of veterinary clinical medicine at the University of Illinois.
According to the CDC’s Uyeki, studies of the H5N1 genetic sequences in the mink outbreak “do not indicate any changes that suggest increased ability to infect the upper respiratory tract of humans.”
That change is a must if a bird flu virus is to spread easily in people.
“The saving grace for humans right now is it seems that it’s really, really difficult for this virus to switch receptor preference,” Webby said.
None of the experts discounted the possibility that H5N1 or another avian flu virus could mutate and spark a pandemic, and many believe the world has not seen its last flu pandemic.
“Should we keep an eyeball out for this? Yes,” Lowe said. “Should we lose our mind over it? Probably not.”