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General Health : Infectious Disease Last Updated: Apr 20, 2011 - 9:38:09 AM


Extreme Immune Reaction Responsible for Spanish Flu Pandemic
By Sara Andrews
Sep 28, 2006 - 3:29:00 PM

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28 Sep, (foodconsumer.org) - The Spanish Flu Pandemic, which claimed millions of lives in 1918-19 was triggered off by an extreme reaction of the immune system to the influenza virus, new research has found. The pandemic was caused by H1N1 virus and claimed 50 million lives.

Researchers said that the reason the virus proved to be so deadly was that it activated genes associated with programmed cell death. In the usual circumstances these genes would have killed off infected cells and helped the body defend itself against the flu. However in this instance the immune system reacted too rapidly and resulted in extensive damage, researchers said.

"The host's immune system may be overreacting and killing off too many cells, and that may be a key contributor to what makes this virus more pathogenic," said lead researcher of the study Dr John C. Kash, Ph.D., of the University of Washington. The findings of the study appear in the Sept. 28 issue of Nature.

The period during 1918-1919 was a watershed for the flu pandemic. The deadly Spanish Flu Pandemic, which was triggered off by a lethal strain of the subtype H1N1 of the species Influenza A virus occurred that year.

Almost 20 percent of the world's population suffered and 5 percent of them were killed. The strain was unusual in killing many young and healthy victims, unlike common influenzas that kill mostly newborns and the old and infirm.

Shockingly, seemingly healthy people would be struck suddenly and within hours be too feeble to walk. A great many succumbed in 24 hours. Scientists were puzzled as to how such a lethal strain came to be. It was only in February 1998 that The Molecular Pathology Division of the US Armed Forces Institute of Pathology (AFIP) was able to recover samples of the 1918 influenza.

The samples were obtained from the frozen corpse of a Native Alaskan woman buried for nearly eight decades in permafrost near Brevig Mission, Alaska. In February 2004, the journal Science reported that two research teams had made it possible for the synthesis of the hemagglutinin protein responsible for the 1918 outbreak of Spanish Flu.

In October 2005, researchers announced success in reconstruction of the genetic sequence of the 1918 flu strain. But all this while scientists never understood why the virus had proved so lethal.

Dr Kash's team attempted to answer this question through their experiments on mice. They simulated the 1918-19 viral infection in the laboratory animals in the hope that understanding the mechanism would allow for a better preparation for possible H5N1 bird flu pandemics in future.

"We're trying to find targets in the host, instead of just in the virus itself," said co-author Michael G. Katze, of the University of Washington. "Then you could have a one-two punch that affects the viral infection, but also dampens the host immune-system response."

Researchers conducted a functional genomic analysis on the infected lung cells of the mice. The aim was to observe which genes were activated in response to the infection. The virus activated several genes related to immune responses, the researchers said. But genes related to programmed cell death were also activated.

Scientists have often speculated that the virus proved fatal since it was followed by a secondary infection, which undermined the immune system.

Dr Christopher Basler, a co-author from Mount Sinai School of Medicine, New York, said that the next step was to examine why the immune system behaved in this bizarre manner. "Our next step is to repeat these experiments, but deconstruct what the immune system is doing so that we can understand why it is reacting so strongly, yet failing to fight the infection," he said, adding that it may be vital to understand this step in the fight against influenza.

"This could help us develop more targeted therapies to combat pathogenic infections, including different types of influenzas or perhaps avian influenza."




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