1918 "Spanish" influenza pandemic down to pig flu RNA
The joining of genetic sequences from pig and human influenza created the deadly strain that killed up to 40 million people around the world in 1918 and 1919, say Australian researchers.
Unlike other flu outbreaks, which prey heavily on the old and the young, the 1918 "Spanish" flu killed many healthy people in their prime. "It tended to give people pneumonia," says virologist Mark Gibbs, who led the research at the Australian National University in Canberra. "That suggests that it infected much deeper in the lungs than influenza normally does - that it had a different tissue specificity."
Flu pandemics are thought to arise when a human flu virus acquires a bird flu gene, which helps it evade human immunity. Smaller pandemics in 1957 and 1968 were triggered this way. But the ANU team found no trace of genetic material from avian flu in a key gene that helped the 1918 virus infect cells. Instead, they identified a fragment of a gene from a pig flu strain.
The new analysis boosts researchers' knowledge of the way human influenza can mutate - which will be vital for understanding how another pandemic might arise in the future, says the team.
Jeffery Taubenberger of the Armed Forces Institute of Pathology in Rockville, Maryland isolated gene sequences for the 1918 virus in 1987. These samples were found in lung biopsies from two American soldiers who succumbed in 1918, and in the lungs of a third victim who was exhumed after 80 years from a grave in the permafrost soil of Alaska.
When Taubenberger analyzed the 1918 gene sequences - specifically a gene called hemagglutinin, which helps the virus infect cells - he found no evidence that it came from birds, and no clues regarding the source of the virus's aggressiveness.
Gibbs took a different approach. Rather than analyzing hemagglutinin as a whole, he used special software to see if different parts of the gene came from different sources. He found the middle half of the gene seemed to come from a pig virus.
This pig segment might alter the virus's tissue specificity - pushing it deeper into the lungs - and also help the virus escape human immunity. Gibbs believes the virus acquired that gene segment just months before the pandemic started, and "it seems very likely that this triggered the pandemic."
However, some researchers are doubtful. Taubenberger says the middle part of the hemagglutinin gene appears pig-like because this gene has evolved more slowly in pig viruses.
Gibbs counters that less than ten per cent of the 1918 hemagglutinin gene would evolve slowly (and therefore appear pig-like) for this reason, whereas his results show that fully half the gene comes from pigs.
Journal reference: Science
(vol 293, p 1842)