The influenza virus might have started in fish. Researchers trawling genetic databases have discovered a distant relative of influenza viruses — which are responsible for seasonal flu, not to mention the avian flu roiling the globe — in sturgeon1.
The authors also found that the wider virus family that includes influenza probably originated hundreds of millions of years ago in primordial aquatic animals that evolved well before the first fish.
Viruses in this group seem to be especially adept at jumping between hosts, says Mary Petrone, a virologist at the University of Sydney, Australia, who co-authored the preprint describing the findings. Knowing about ancient host jumps could help scientists identify viruses with the potential to spark new human epidemics. The study was posted on 16 Feburary to the preprint server bioRxiv and has not yet been peer reviewed.
Influenza’s origins story
Like many virologists, Petrone spent the first couple years of the pandemic intensively studying SARS-CoV-2. But when she moved to Australia to do postdoctoral research, Petrone wanted to steer clear of human infections and spend time in one of the country’s most famous ecosystems. “After working on COVID for two years, I thought going to coral reefs to do fieldwork sounded really good,” she says.
Corals are part of a phylum called Cnidaria, whose ancestors branched off from other animals around 600 million years ago. Petrone hoped that studying corals could reveal the deeper history of viruses that infect animals — particularly those with RNA genomes. This viral group includes numerous human and animal pathogens.
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Petrone’s first call was not to a diving shop but to Zoe Richards, a coral-reef researcher at Curtin University in Bentley, Australia, who provided samples of two coral species collected off the coast of Western Australia. Analysis of RNA collected from the corals found evidence of infection with viruses that belong to a grouping called Articulavirales, which includes influenza’s family of viruses and a group called Quaranjaviruses. The latter group’s members circulate in ticks and occasionally spill over into humans, birds and other vertebrates.
The new analysis suggests that coral-infecting viruses are part of an ancient viral family that probably emerged around 600 million years ago, and later gave rise to other members of Articulavirales, including influenza and Quaranjaviruses.
Secrets of the hagfish
The discovery got Petrone wondering whether influenza viruses might also have been born at sea. There was already some evidence for this. In 2018, researchers identified a distant relative of influenza in hagfish2. These slimy, jawless creatures descended from an early lineage of vertebrates, and the study’s authors hinted that influenza evolved alongside vertebrates.
Searching genetic databases, Petrone found influenza-related RNA sequences in samples from Siberian sturgeon (Acipenser baerii). Sturgeon are jawed vertebrates, more closely related to humans than hagfish are. But the sturgeon virus had branched off from the main influenza family tree before any other known influenza virus, including the hagfish virus.
The discovery of the two early lineages of influenza suggest that influenza probably infected aquatic animals, including fish, before moving onto land, says Petrone. But it’s not clear whether influenza moved onto land with early terrestrial vertebrates, or jumped from sea to land more recently.
To determine this, researchers will need to look for relatives of influenza in more animals and gain a better understand how the virus spreads between host species, researchers say.
Born at sea
Jie Cui, an evolutionary virologist at the Pasteur Institute of Shanghai in China, agrees that influenza and its wider family probably emerged from the sea. In 2021, his team analysed deep-sea lobster genomes and identified viruses that are part of influenza’s wider group3. “There is great untapped viral diversity in aquatic environments,” he says.
Robert Gifford, an evolutionary virologist at the University of Glasgow, UK, says it would be surprising to find a major group of viruses that didn’t arise in aquatic environments because of the ancient nature of marine life. “The study provides compelling evidence that influenza viruses have an aquatic origin.”
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Identifying ancient host jumps could also help researchers gauge the risk that certain viruses pose to humans, researchers say. Petrone’s team found signs that Quaranjaviruses that infect ticks might have jumped to the creatures after first circulating in crustaceans.
Uncovering such jumps shows that the study of aquatic viruses “can help us to better understand the historic emergence and evolution of viruses with zoonotic potential”, adds Chantal Vogels, an arbovirologist at the Yale School of Public Health in New Haven, Connecticut.
Gifford agrees that studies such as Petrone’s could help to identify viruses that have the capacity to spark epidemics in humans and other animals. But he cautions that conclusions about ancient host jumps can change as more of the viral family tree gets filled in, reshuffling relationships.
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