1918 flu re-created!

Scientists resurrect killer genes from 1918 flu pandemic
Wed Oct 6, 2:29 PM ET

PARIS (AFP) - Scientists working in top-security labs say they have recreated pathogens from the 1918 flu pandemic, the greatest plague of the 20th century, in a bid to find out why this strain was so extraordinarily lethal.

Using reverse genetic engineering, the US team took two key genes from the 1918 virus and slotted them into human flu viruses to which lab mice were known to be immune.

The two genes code for a spike-like molecule called haemagglutinin (HA), which binds to specific receptors on the surface of cells in the body, and another protein, neuraminidase (NA).

The mice were injected in the nose with the recombinant viruses.

Within three days, mice that had been exposed to the HA gene were mortally ill. Post-mortems showed the virus had rampaged through their lungs, producing inflammation and haemorrhaging characteristic of the symptoms induced by the 1918 outbreak.

At least 20 million and perhaps as many as 50 million people died in the 1918-1919 pandemic, the highest toll of any disease in the last century.

Scientists say that the disease leapt to humans by mutating from bird flu, possibly after passing through pigs, which are able to harbour both human and avian viruses and thus allow them to swap genes as the viruses reproduce.

For that reason, experts are deeply concerned that the avian flu that has broken out in poultry flocks in parts of Southeast Asia may acquire genes that will make it highly infectious as well as lethal for humans.

The researchers, led by Yoshihiro Kawaoka of the University of Wisconsin at Madison, stress that the experiment is only conclusive for lab mice, not humans.

Nevertheless, they say, it adds strongly to suspicions that what made the type A 1918 virus strain so extraordinarily vicious was the unique profile of its HA gene.

That finding opens up good avenues for diagnostic tools for spotting emergent viruses with this genetic signature, thus tackling an outbreak in its early stages.

"Once the properties of the (1918) HA gene that gave rise to its lethal infectivity are better understood, it should be possible to devise effective control measures and to improve global surveillance networks for influenza viruses that pose the greatest threat to humans as well as other animal species," the authors say.

The study is published on Thursday in Nature, the British science weekly.

A previous study into the 1918 strain, published in Science in February, also pointed the finger at HA, theorising that only minor changes in its structure were needed for it to start binding with human cells as well as bird cells.

The latest research takes this a step forward, for it actually recreated the suspect gene and tested it on animals.

In order to prevent their creation from escaping into the open, Kawaoka's team carried out the genetic resurrection at a Biosafety Level Four facility -- the most secure level -- at the National Microbiology Laboratory in Winnipeg, Canada and at an "enhanced" Level Three lab at the University of Wisconsin.

By some estimates, the 1918 pandemic, called "Spanish flu" in the probably erroneous belief that it began in Spain, infected up to a billion people, which was half the world's population at the time.

The strain was especially lethal for healthy young adults, killing many of the World War I troops who had survived trench warfare, but leaving the very old and the very young -- the more usual victims of flu -- unscathed.

The reason for this is unclear. One theory is that the immune system reacts differently at various stages of life, and that young people may have been particularly vulnerable to an uncontrolled response by cytokines, the proteins that play a big role in causing inflammation.

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