Deadly Spanish Flu code cracked

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Deadly 'flu code cracked TheStar.com - News - Deadly 'flu code cracked

January 17, 2007

Joe Hall

Toronto Star

 

http://www.thestar.com/printArticle/172085

Canadian scientists have helped unlock a key secret to history's deadliest

influenza outbreak and how it killed so quickly and efficiently.

The savage Spanish Flu pandemic that swept the globe at the end of the First

World War killed about 50 million people - many in a matter of hours - when

their immune systems began attacking their own lungs, a paper published today in

the journal Nature says.

The paper, which studied monkeys infected with a reconstructed version of the

1918 flu at Canada's National Microbiology Laboratory in Winnipeg, may also

offer clues on how to stem future outbreaks.

" This research provides an important piece in the puzzle of the 1918 virus,

helping us to better understand influenza viruses and their potential to cause

pandemics, " said Darwyn Kobasa, a research scientist with the Public Health

Agency of Canada in Winnipeg and the lead study author.

" Thanks to recent technological advancement, we are able to study this virus

and how it wreaked havoc around the globe, " Kobasa said in a statement.

In the early 1990s, University of Toronto geographer Kirsty Duncan, then at

the University of Windsor, located seven young coal miners who had died in 1918

and were buried in a permafrost cemetery in the village of Longyearbyen, Norway

Duncan was able to isolate bits of viral RNA from the miner's preserved flesh,

which has been used to construct copies of the original 1918 virus.

But scientists at the " Level 4 " Winnipeg lab - which can house and study the

earth's most lethal pathogens - used viral RNA from archived tissues of first

war soldiers to resurrect the 1918 pathogen, Kobasa said in an interview.

They then used that virus to infect several macaque monkeys and study its

effects on the primates.

What they found was that the virus unleashed an attack of the body's immune

system on the lungs - causing fluids to build up in the respiratory tract.

The flu's victims, the study says, would essentially have drowned in their own

fluids.

" This study in macaques . . . suggests that the host immune response is out of

control in animals infected with the virus, " Michael Katze, a microbiologist at

Seattle's University of Washington said in a release on the study.

" Our analysis revealed potential mechanisms of virulence, which we hope will

help us develop novel antiviral strategies to both outwit the virus and moderate

the (human) immune response, " said Katze, one of the study's authors.

The same immune response identified in the Winnipeg monkeys has also been seen

in people infected with the H5N1 virus - or avian flu - that is present today in

Asia and has killed 150 people.

" What we see with the 1918 virus in infected monkeys is also what we see with

H5N1, " says Yoshihiro Kawaoka, a University of Wisconsin-Madison virologist who

also participated in the study.

Unlike the 1918 Flu, the avian flu has so far been unable to spread easily

between humans.

But Kawaoka suggests that the overwhelming immune response seen in both

varieties may be a signature of all virulent influenza viruses.

Dr Donald Low, chief microbiologist at Toronto's Mount Sinai hospital said the

study helps confirm a theory that has been proposed for some time about the

Spanish flu's rapid and deadly progress.

Low said the study contained strong evidence to the back up the so-called

" cytokine storm " theory of pandemic flu outbreaks.

" There's some pretty nice evidence (in the paper) to show exactly what is

happening, " Low says.

Although it " doesn't put it's finger on the exact cause " , Low said the paper

strongly suggests that a protein produced by pandemic viruses, known as NS1, is

" essentially hijacking the immune system. "

Low said the protein inhibits the immune system's ability to kill off the

invading virus, causing the cytokine messengers that trigger the body's

inflammatory response to flues to keep on going.

Cytokines are chemical messengers in the body that trigger - among other

things -- appropriate responses to invasive agents. And the cytokines involved

in reacting to influenzas typically promote an inflammatory response in the

lungs and other infected organs, Low said.

With the NS1 protein preventing the influenza virus from being killed off,

however, Low said the cytokines triggering lung inflammation just keep on acting

until they eventually destroy the pulmonary lining.

Low said the study also looked at monkeys infected with normal human influenza

and that their cytokine response waned after several days as the virus was

irradiated in the body.

" But if you look at the monkeys with the 1918 strain, it's gone to hell in a

hand cart, you've got bleeding in the lung, you've got fluid in the lung there's

no evidence of any repair. "

Low said the study suggests that the virus' protective NS1 protein might be a

prime target for any therapies to protect people against future pandemic flues.

" If we find that what's predictive of real bad disease is this protein that

being produced by the virulent strain . . . in theory there could be a drug

which could actually neutralize NS1. "

In all, seven monkeys were infected with the 1918 flu at the Winnipeg lab, and

all developed symptoms within 24 hours. All were so sick after eight days that

they had to be put down for humane reasons.

This type of timetable reflects many reports of the flu's behaviour in the

1918 outbreak.

 

 

 

 

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