A new study suggests that a avian flu virus mutated and spread among mammals, causing mass deaths of elephant seals in South America.
The study provides the first genetic and epidemiological evidence of the transmission of avian influenza viruses between mammals, and its findings come with a warning: The virus, called H5N1, could mutate in a similar way and cause widespread infections in other mammalian species, including humans.
The avian influenza virus is the cause of an ongoing outbreak among dairy cows in the United States. Since March, the virus has been detected in dairy cows in nine states and in wastewater from several others.
While it's possible the virus was already spreading from cow to cow, federal officials say the latest outbreak is more likely to be caused by contaminated milk.
H5N1 is presumed to have also spread among minks on Spanish fur farms, but the new study is the first to bring together a range of evidence supporting mammal-to-mammal transmission.
The study was published online Saturday and has not been peer-reviewed, but genetic analysis of the virus and the scale and timing of infections in South American marine mammals all suggest that the animals caught the virus from each other, rather than from infected birds, the researchers said.
“This is a combination of facts that provides compelling evidence that there is some mammal-to-mammal transmission,” said Marcela Uhart, who led the new study and directs the Latin American Wildlife Health Program at the University of California, Davis.
In 2022 and 2023, the H5N1 virus killed more than 30,000 sea lions in Peru and Chile, as well as porpoises, dolphins and otters. The virus traveled south along the Pacific coast, then north along the Atlantic coast, through Argentina and into Uruguay and Brazil.
A “viral tsunami” killed more than 17,000 elephant seals in Argentina's Patagonia region last October, Dr Uhart said, adding that the figures made it unlikely the virus jumped from birds to marine mammals every time.
Mammal-to-mammal transmission “is pretty much the only way to explain how it spread and continued to spread across the southern tip of the continent,” she said. “There's honestly very little other reason why this happened.”
In the new study, Dr. Uhart and her colleagues studied virus samples from elephant seal pups and terns, and genetic analysis suggests that H5N1 may have jumped from wild birds to marine mammals on the Pacific coast of South America at least three times before evolving to spread among elephant seals.
The team presented some of these data at a small conference, but other researchers resisted the idea that marine mammals are infecting each other, Dr. Uhart said.
Some scientists suggested that all the mammals had gotten the disease from the birds, but the majority of the terns died about three weeks after the mass die-offs of sea lions and elephant seals.
In fact, Dr. Uhart and her colleagues found evidence suggesting that the virus may have jumped back from marine mammals to birds — an unwelcome development, as infected birds could spread the virus wherever they travel.
The researchers found the H5N1 virus in the trachea, lungs and brains of the marine mammal carcasses. It's unclear whether the virus was airborne or spread in some other way, but laboratory experiments have shown that the virus can be transmitted through the air and by direct contact between ferrets.
The researchers found that the avian influenza viruses collected from marine animals contained 18 mutations that make them easier to infect and spread to mammals and increase the severity of the disease.
Dr Malik Peiris, a virologist at the University of Hong Kong and an expert on bird flu, who was not involved in the study, said the “high number of mutations” was a concern.
In contrast, infected cows showed few mutations that would suggest mammalian adaptation, “but it may only be a matter of time,” Dr Peiris said.
None of the mutations were found to affect hemagglutinin (HA), the viral protein that binds to human and animal receptors. Other studies have suggested that changes in HA may be important for H5N1 to spread among humans and may precede mutations in other parts of the virus.
But “even though the HA has not changed, there are other mutations that could be of concern,” said Agustina Rimondi, a virologist at the INTA-CONICET virology institute in Buenos Aires, who led the genetic analysis.
With each infection, the virus has new opportunities to evolve and acquire mutations that could allow it to infect people more easily, she said.
Among the mutations found in the marine mammal virus are two that alter an enzyme the virus needs to replicate — D701N and Q591K. Both mutations are thought to be alternatives to another mutation called E627K, which is thought to be a critical change required for the virus to infect mammals.
The mutation merits further investigation but may not result in the necessary changes to the HA and is not necessarily a precursor to person-to-person transmission, said Richard Webby, an influenza expert at St. Jude Children's Research Hospital who was not involved in the study.
“We think that changes in the HA receptor facilitate the emergence of other receptors, but not the other way around,” he said.
Dr. Webby warned against thinking of all mammals as a homogenous group.
“I don't think marine mammals are the same as humans in terms of susceptibility,” he said. “The virus may replicate in marine mammals but not in a way that makes it more infectious to humans.”