Australian National University Scientists Find Genetic Trigger For The 1918 Spanish Flu

The 1918 Spanish Flu pandemic was the worst disease outbreak in history killing more than 20 million people as it spread around the world in 1918 and 1919.

The virus was not isolated and preserved at the time of the outbreak and scientists believed it had been lost, then in 1997 a team from the USA recovered some of its genetic material. The material was extracted from a female victim whose body was buried in permafrost in Alaska and from samples taken in1918 from two US soldiers who died in the pandemic. The US scientists reconstructed part of the genetic data (a gene sequence) of the virus and compared this with the gene sequences of other strains of influenza virus. However their analysis did not shed light on what triggered the pandemic or why it was so severe.

Dr Mark Gibbs, Mr John Armstrong and Professor Adrian Gibbs at the ANU's School of Botany and Zoology have discovered that one of the 1918 Flu genes was a hybrid that was produced from parts of two other influenza viruses, in a process called "recombination".

Their analysis indicated that this "gene splicing" occurred just before the 1918 pandemic and one of the two progenitors of the 1918 virus was an influenza strain that probably infected pigs. The results suggest that the outbreak was triggered by the recombination.

"The recombination was within the gene that codes for the haemagglutinin protein of the virus. Changes in this protein are known to increase the virulence of the influenza," Dr Gibbs said. "Recombination has not been detected before within the genes of the virus. Now the possibility that current strains may recombine needs to be investigated as new recombinant viruses may pose a threat. We may have discovered part of the reason for the extreme virulence of the 1918 Spanish Flu virus."

The team developed specialised computer software for analysing genetic data. "These programs work like those used for detecting plagiarism in a manuscript," Dr Gibbs said. "We use them to compare the sequences of a set of genes and they can detect whether one of the genes came from two sources.Recombination in influenza genes is difficult to detect, because the genetic data is carried in a code of only four chemicals (like four letters) and the genes are all very similar."

The ANU team now intends to analyse all influenza sequences to assess the risk of similar recombination events that might produce future influenza outbreaks. "This is a big task as more than 6,000 influenza genes representing several thousand different influenza strains have been isolated and sequenced since the 1930s," said Dr Gibbs.

The research is reported in the latest edition of the US Journal, Science.

For more background information and links: http://www.anu.edu.au/pad/media/releases2001/flubackgrounder.htm