Lethal secrets of 1918 flu virus
http://news.bbc.co.uk/2/hi/health/6271833.stm
Scientists who recreated "Spanish flu" - the 1918 virus
which killed up to 50m people - have witnessed its
remarkable killing power first hand.
The lungs of infected monkeys were destroyed in just days as
their immune systems went into overdrive after a Canadian
laboratory rebuilt the virus.
The reason for the lethal nature of the 1918 flu was never
fully understood.
But the experts behind this test say they have found a human
gene which may help explain its unusual virulence.
They are hoping to help control any future pandemic and
believe that the strain may hold clues that will help them.
Despite the large number of casualties at the time, doctors
had no way to preserve tissue samples taken from infected
patients, so researchers used an ingenious method to
overcome this.
Frozen body
The preserved body of a flu victim buried in Alaskan
permafrost was exhumed, and they painstakingly extracted the
genetic material needed to work out the structure of the
H1N1 virus.
Then, in a maximum "biosafety" facility at Canada's National
Microbiology Laboratory they reconstructed a fully
functioning virus, and infected macaque monkeys to see what
would happen.
Writing in the journal Nature, they reported that the
results were startling. Symptoms appeared within 24 hours of
exposure to the virus, and the subsequent destruction of
lung tissue was so widespread that, had the monkeys not been
put to sleep a few days later, they would literally have
drowned in their own blood.
The results match those seen when mice were infected in an
earlier study and are very similar to those described in
human patients at the time the virus was at its height.
Dangerous virus
Darwyn Kobasa, a research scientist with the Public Health
Agency of Canada, and lead author of the research, defended
the decision to recreate one of the most dangerous viruses
in history.
He said: "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."
However, it is not the virus that is directly causing the
damage to the lungs - it is the body's own response to
infection.
Immune system proteins that can damage infected tissue were
found at much higher levels following H1N1 infection
compared with other viral infections.
Analysis at the University of Wisconsin at Madison (UW)
revealed that a key component of the immune system, a gene
called RIG-1 appeared to be involved.
Levels of the protein produced by the gene were lower in
tissue infected with the 1918 virus, suggesting it had a
method of switching it off, causing immune defences to run wild.
This ability to alter the body's immune response is shared
with the most recent candidate for mutation into a pandemic
strain, the H5N1 avian flu.
Experts are worried that if the virus changes so that it can
infect humans easily, it could again be far more lethal than
normal seasonal flu.
"What we see with the 1918 virus in infected monkeys is also
what we see with H5N1 viruses," said Yoshihiro Kawaoka, who
led the analysis at UW.
"Things may be happening at an early time point (in
infection), but we may be able to step in and stop that
reaction."
Preparing for pandemic
Dr Ronald Cutler, an infectious diseases researcher at the
University of East London, said: "Knowing how that over
stimulation takes place could lead to the development of new
methods to treat these diseases so we are better prepared
for any future pandemic."
Dr Jim Robertson from the UK's National Institute for
Biological Standards and Control, said the decision to
recreate the virus was justified.
"Many influenza virologists remain nervous about creating
and experimenting with a reconstructed 1918 Spanish flu
virus, an extremely dangerous virus which disappeared from
the world long ago.
"However, it cannot be denied that the information that has
been derived from this experiment is exciting and represents
an important milestone in understanding the severity of
these highly pathogenic types of influenza viruses."
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