Fresh research suggests something revolutionary happened to avian influenza viruses around the time of a massive equine flu outbreak in North America in the 1870s, which brought the US economy to its knees.
The study, published in the journal, Nature, breaks new ground in analyzing the evolutionary relationships of influenza virus across different host species over time.
It suggests equine influenza may have had a greater role in influenza development than originally thought.
The study challenges the notion that the virus moves largely one way from wild birds to domestic birds rather than with spillover the other way.
“We now have a really clear family tree of theses viruses in all those hosts – including birds, humans, horses, pigs – and once you have that, it changes the picture of how this virus evolved,” said Michael Worobey, a professor of ecology and evolutionary biology at the University of Arizona, who co-led the study with Andrew Rambaut, a professor at the Institute of Evolutionary Biology at the University of Edinburgh.
“The approach we developed works much better at resolving the true evolution and history than anything that has previously been used,” he told Phys.org.
“Once you resolve the evolutionary trees for these viruses correctly, everything snaps into place and makes much more sense.”
Worobey and his team team analyzed more than 80,000 gene sequences representing the global diversity of the influenza A virus and analyzed them with their newly developed approach.
The influenza A viruses fall into 17 so-called HA subtypes – H1 through H17 – and 10 subtypes of NA, N1-N10. These mix and match, with the greatest diversity in birds.
The new flu virus family tree reveals which species moved to which host species and when, showing that, for several of its eight genomic segments, avian influenza virus is not nearly as ancient as often assumed.
“What we’re finding is that the avian virus has an extremely shallow history in most genes, not much older than the invention of the telephone,” Worobey said.
The research team found a strong signature in the data suggesting something revolutionary happened to avian influenza, with most of its genetic diversity being replaced by some new variant in a selective sweep in an extremely synchronous event.
Worobey says there is a correlation of that sudden shift with the so-called Great Epizootic of 1872, which affected countless thousands of horses across North America.
“In the 1870s, an immense horse flu outbreak swept across North America,” he said. “City by city and town by town, horses got sick and perhaps 5 percent of them died. Half of Boston burned down during the outbreak, because there were no horses to pull the pump wagons. Out here in the West, the US Cavalry was fighting the Apaches on foot because all the horses were sick.
“This happened at a time when horsepower was actual horse power. The horse flu outbreak pulled the rug out from under the economy.”
Worobey said the new flu evolutionary trees showed a global replacement of genes in the avian flu virus coinciding closely with the horse flu outbreak, which the analyses also reveal to be the closest relative to the avian virus.
“Interestingly, a previous research paper analyzing old newspaper records reported that in the days following the horse flu outbreak, there were repeated outbreaks described at the time as influenza killing chickens and other domestic birds,” he said.
“That’s another unexpected link in the history, and there is a possibility that the two might be connected, given what we see in our trees.”
Worobey stressed that the evolutionary results did not determine whether the virus jumped from horses to birds or vice versa, but a close relationship between the two virus species was clearly there.
However, the analysis confirmed a shared ancestor for almost all avian flu strains and the H7N7 virus that struck down the horses.
Oliver Pybus, an evolutionary biologist at the University of Oxford, in Britain, described Worobey’s study as highly persuasive.
“We now have this idea that the source for a lot of influenza virus we see now worldwide is potentially equine, whereas the dogma has been for so long that its avian,” Pybus told Nature.com. “It’s a fascinating study, and quite a surprise.
“It shows the evidence for a pig origin is a lot weaker, but it’s almost impossible to completely shut the door on that.”
Richard Lenski, an evolutionary biologist at Michigan State University, acknowledged: “Transmission between horses and humans seems to have been key to some epidemics when horses were an intimate part of our lives.”
The research also shed light on longstanding mysteries around the great human influenza pandemic of 1918, which swept the globe.
It has not been possible to narrow down even to a hemisphere the geographic origins of any of the genes of the pandemic virus.
“Our study changes that,” Worobey said. “It is now clear that most of its genome jumped from birds very close to 1918 in the Western Hemisphere, and there is a suggestion that it was North America in particular.”
The team also challenges the accepted wisdom of wild birds as the major reservoir for the flu virus. Instead, the genetic diversity across the whole avian virus gene pool in domestic and wild birds often appeared to trace back to earlier outbreaks in domestic birds.
“People tend to think of wild birds as the source of everything, but we see a very strong indication of spillover from domestic birds to wild birds.
“It turns out the animals we keep for food and eggs may be substantially shaping the diversity of these viruses in the wild over time spans of decades. That is a surprise.”
Michael Worobey, Guan-Zhu Han, Andrew Rambaut. A synchronized global sweep of the internal genes of modern avian influenza virus. Nature, 2014; DOI: 10.1038/nature13016