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Scientists Reconstruct 1918 Flu Virus for Potential Future Pandemic

Posted on: Thursday, 6 October 2005, 09:00 CDT

Scientists reconstruct 1918 flu virus for potential future pandemic

LOS ANGELES, Oct. 5 (Xinhua)-- Scientists have partially reconstructed for the first time the Spanish flu virus that killed 20 to 50 million people worldwide in year 1918, and discovered why the virus could be so lethal.

This finding, appearing in the Oct. 7 issue of the journal Science, will provide essential information for flu drug and vaccine research, and help contain a potential flu pandemic in the future, experts said on Wednesday.

The Spanish flu virus is more closely related to avian flu viruses than other human flu viruses. Scientists have predicted that it is only a matter of time before an avian flu outbreak occurs in humans and develops into a global pandemic.

Therapies against a new flu strain would need to disarm the parts of the virus that do the most damage to the body. In order to learn which components of the virus would be the best targets for such therapies, Terrence Tumpey of the US Centers for Disease Control and Prevention and colleagues revisited the 1918 Spanish flu virus.

Based on the genome sequence of the virus, the group resurrected a live virus with its all eight genes. The genome sequence information was recovered in fragments from lung autopsy materials and lung tissues from a flu victim who was buried in the Alaskan permafrost in 1918.

To reconstruct the virus, the researchers used an approach called "reverse genetics," which involves transferring gene sequences of viral RNA into bacteria and then inserting combinations of the genes, often after manipulating them, into cell lines, where they combine to form a virus.

They also produced variations of the virus for comparison, with certain Spanish flu genes replaced by the corresponding genes from other flu viruses. Then they studied the viruses' effects in mice, chick embryos and human lung cells and identified the constellation of genes that was responsible for the Spanish flu virus' extreme virulence.

One gene associated with high virulence was the HA gene, which encodes the hemagglutinin surface protein that helps the virus attach to cells and replicate properly, the researchers found.

This gene seemed to be responsible for much of the severe lung damage reported in people infected with the Spanish flu. The three genes encoding the viral "polymerase" enzymes, which form the virus' basic replication machinery, were also found to be important for high virulence.

"Given that HA is responsible for so much pathology in the lung, if we could identify the mechanism for how that happens and then block it, perhaps it would be useful for antiviral development," Tumpey said.

Although more research needs to be done on antivirals and vaccines for a future flu pandemic, Tumpey noted some encouraging signs.

The flu antiviral drugs, oseltamivir and amantadine, have been shown to be effective against viruses carrying certain genes from the Spanish flu virus. And, vaccines containing the Spanish flu HA gene, as well as another gene from this virus, were protective in mice, he said.

Source: Xinhua News Agency - CEIS

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