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Pandemic flu viruses brew for years before going global

July 13, 2009 By Heidi H Ledford This article courtesy of Nature News.

Monitoring more viral genes could provide early warning of dangerous outbreaks.

Family trees for pandemic influenza have revealed that components of deadly flu viruses probably lurk in humans and other animals for years before they emerge as a worldwide threat to human health. The work suggests that a more thorough characterization of circulating flu viruses could provide clues to an emerging pandemic before it hits.

According to results published this week in Proceedings of the National Academy of Sciences1, two genes from the 1918 influenza virus, which killed an estimated 50 million people, would have been present in human and swine flu viruses at least 6 years earlier.

During the intervening years, the authors of the work suggest, swine and human flu viruses would have swapped genes with avian viruses, ultimately giving rise to the dangerous assortment of genes carried by the 1918 virus.

This work suggests that the generation of pandemic strains could be much more involved than was previously thought.
Raul Rabadan
Columbia University College of Physicians and Surgeons

"This work suggests that the generation of pandemic strains and the adaptation to humans could be much more involved than was previously thought," says Raul Rabadan, a biomedical informatician at Columbia University College of Physicians and Surgeons in New York, who was not involved in the study. "It reinforces the idea that systematic surveillance, not only in humans but in other mammalian and avian hosts, is key to identifying possible pandemic strains and their future evolution."

Yi Guan of the University of Hong Kong, Robert Webster of St. Jude Children's Research Hospital in Memphis, Tennessee, and their colleagues compiled the available data on known bird, swine and human flu viruses and created family trees based on DNA sequence information. By estimating the amount of time it would take to accumulate the differences in DNA sequences found in human and swine viruses, the researchers determined that a precursor to at least one 1918 flu gene was present in mammals before 1911. Another had been circulating in humans since the 19th century.

Mix and match

The results run counter to previous hypotheses that the human 1918 flu strain had evolved directly from a bird flu virus2. Instead, the new findings suggest that an avian strain entered pig and human populations, and then swapped genes with mammalian flu viruses before becoming a pandemic.

Meanwhile, elements of the 1957 pandemic flu virus — also thought to be a mosaic of human and avian flu genes — were probably introduced into human populations two to six years before the pandemic, the researchers found.

These analyses were completed before the current pandemic swine flu strain made its mark, but the researchers argue that their results have implications for future pandemics. Results from 1918 and 1957 pandemic flu suggest that public-health authorities should track the sequences of all influenza virus genes in emerging strains, the authors argue, rather than focusing largely on the gene that encodes the haemagglutinin' protein, which is critical for vaccine production, as is the current practice.

Nevertheless, reliance upon patchy data from historical flu viruses has its limitations. Michael Worobey, who studies pathogen evolution at the University of Arizona in Tucson, says that his own analyses have also suggested that human and swine forms of H1N1 shared a common ancestor years before 1918. But he remains unconvinced by the series of genetic swaps proposed by the paper. "Using different assumptions, you can get very different results," he says. "We can't say much for certain about these events given the current data."


  1. Smith, G. J. D. et al. Proc. Natl Acad. Sci. USA 106, 11709-11712 (2009).
  2. Taubenberger, J. K. et al. Nature 437, 889-893 (2005).


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