TORONTO - The precursors of pandemic flu viruses may circulate in humans for years before picking up all the genetic changes needed to ignite a pandemic, a new study suggests.
The authors argue that the last three pandemics -- including the infamous 1918 Spanish flu -- emerged in this gradual manner.
They also say their findings contradict the notion that the Spanish flu virus jumped directly from birds into people. Instead, they say, it evolved in a gradual manner over years, with some of the genes likely coming from the virus responsible for the pandemic that preceded 1918. That pandemic, which occurred in 1889, is believed to have been caused by an H3 virus.
"It's always been contentious," lead author Gavin Smith said of the theory that the Spanish flu virus came directly and intact from birds, rather than through a serious of gene-swapping events known as reassortments.
"It's never been a consensus view of people in the research community."
However, the researcher who led the effort to find and sequence the 1918 virus said this new work, done by calculations drawn from virus family trees -- a process called phylogenetics -- can only generate hypotheses about how the Spanish flu virus emerged.
"The fundamental problem in terms of dating the emergence of 1918 with all of these models ... (is) that the crucial data that we would need to understand the origin of the 1918 flu are influenza samples from before 1918," said Jeffery Taubenberger, an influenza research at the U.S. National Institutes of Allergy and Infectious Diseases.
"And until such time that those sequences are available, I think that phylogenetics is not going to be able to answer with specificity the question about the origin of the 1918 virus."
The new paper, published in the journal Proceedings of the National Academy of Sciences, is by researchers from the University of Hong Kong, Shantou University in China, and St. Jude Children's Research Hospital in Memphis, Tenn.
Smith is an evolutionary biologist and virologist at the University of Hong Kong. He was also lead author of a paper published last month in Nature that estimated the new swine flu virus has been circulating in people probably since about January of this year.
The current research used the same techniques as were employed in the Nature paper. Smith and his colleagues looked at gene sequences for all eight genes in the flu viruses responsible for the 1918, 1957 and 1968 pandemics, tracing back their lineages through the available banked sequence data.
Smith said the work suggests all three of the pandemics of the 20th century emerged through reassortment, the swapping of genes that can occur when an animal or a human is infected with two different strains of flu at the same time.
While it is widely accepted the 1957 and 1968 strains were reassortant viruses, some contend the 1918 virus was an avian virus that mutated to the point where it was able to infect people.
Smith and his co-authors also compared the viruses to current seasonal H1N1 viruses and H1N1 viruses known to circulate in pigs and came to a somewhat startling conclusion.
Current seasonal H1N1 viruses and swine viruses are not the distant offspring of the 1918 virus, they said. Rather, the gene dating techniques suggest the 1918 H1N1, current seasonal H1N1s and the H1N1s circulating in pigs all had a common ancestor, making them more like cousins or distant relatives.
If they are right, that suggests those viruses were all circulating during the 1918 pandemic, which could explain uneven patterns of disease seen at the time.
"There was variation in the severity of the pandemic," Smith explained in an interview from Hong Kong.
"Some areas had more severe (disease) and others didn't. So it sort of fits into that idea. But again it is inference. And unless you got a lot of isolates from that period, I think it's always going to be impossible to say definitely."
Taubenberger remains skeptical, noting that if modern science can't say where and when the current pandemic virus evolved, it have less chance of cracking the mysteries of 1918.
"Even in this time and age of extraordinary influenza surveillance and rapid genetic analysis, we actually don't know with specificity when that reassortment event (that produced the pandemic virus) occurred, in what species, in what location geographically. We don't know that... in something that just happened right now, in a molecular virology era," he said from Bethesda, Md.
"Since we don't know what happened in 2008 or 2009 in the emergence of this new H1 (virus), we really don't know what happened in 1918 where so much data is not available and probably will never become available."
