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Thursday September 6 6:17 PM ET

Pig, Human Viruses Triggered 1918 Flu Pandemic - Researchers

By Will Dunham

WASHINGTON (Reuters) - The genetic union of pig and human influenza viruses
triggered one of the most deadly disease outbreaks in human history, the 1918
``Spanish'' flu pandemic, according to researchers who warned that another
flu outbreak is inevitable.

In a study appearing in the journal Science on Thursday, scientists at the
Australian National University in Canberra said a key gene in the virus
responsible for the 1918 pandemic was a hybrid created by the joining
together of genetic sequences of pig and human influenza viruses.

This ``recombination'' may account for the severity of the outbreak, the
researchers said.

The pandemic, whose outbreak came just as World War One was drawing to a
close, killed more than 20 million people as it spread around the globe in
1918 and 1919.

Understanding the cause of past flu outbreaks is vital in the quest to
recognize threatening future outbreaks, said lead researcher Mark Gibbs.

``Another pandemic is inevitable,'' Gibbs told Reuters. ``They are triggered
by changes in the virus, and the virus will change again. ... There were
major pandemics in the 1890s, 1918, 1957 and 1968, and some scientists say
that we are due for another one.''

The study was one of two concerning influenza appearing in Science. In the
second, researchers led by Yoshihiro Kawaoka of the University of Wisconsin
studied a more-recent deadly influenza outbreak, the 1997 Hong Kong
``chicken'' flu. The outbreak killed six out of the 18 people it infected.

Influenza infects humans, pigs, some birds, horses and seals. The Hong Kong
outbreak was the first documented case of an influenza virus jumping directly
from chickens to people. Public health authorities responded by ordering the
slaughter of more than 1 million live poultry to prevent further spread.

Using laboratory mice, Kawaoka's team showed that a tiny change in one of the
virus's 10 genes can make certain strains especially virulent.

``Because the influenza virus constantly mutates, and because only a few
changes can make a non-pathogenic virus highly pathogenic, we should assume
that an outbreak of any new strain or sub-type is potentially dangerous to
humans,'' Kawaoka said.

MEDICAL DETECTIVES

The virus from the 1918 ``Spanish'' flu was not preserved at the time of the
outbreak and long was believed to have been lost to science. But American
scientists in 1997 recovered some of its genetic material from a female
victim whose body was buried in permafrost in Alaska and from samples taken
in 1918 from two U.S. soldiers who died in the pandemic.

These scientists reconstructed part of the genetic data of the virus and
compared it to other strains of influenza virus. But this analysis failed to
reveal what triggered the pandemic and what made it so bad.

Gibbs and colleagues John Armstrong and Adrian Gibbs found that one of the
genes of the virus actually was a hybrid that was produced by recombination
of parts of the genes of two strains of influenza that were circulating just
before the pandemic. Mark Gibbs said the gene was constructed from these
parts while the viruses were replicating.

The researchers said changes in this particular gene can make the virus
unrecognizable to the immune system -- which the body uses to fight off
disease -- and can ratchet up the virulence of the virus.

Gibbs said strains of influenza sometimes are transmitted between pigs and
people.

He said the recombination took place when a host -- one of those pigs or
people -- became infected with both strains at the same time. The two viruses
met up in some of the cells of the host and then the mixture occurred as ``a
kind of replication error,'' he added.

The 1918 flu killed about one in 40 of the people it infected. Current
influenza strains kill about one in 25,000 people infected.

``We need to know why some influenzas are much more virulent than others
because this might help in medical treatment, in the control of the virus
through anti-viral drugs or help us to recognize threatening new outbreaks,''
Gibbs said.


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