(off topic : Science) NYT article on genetic features of HN51 and Human Influenza
- From: "orang37" <orang37@xxxxxxxxxxxxxxxxxxxxxx>
- Date: Tue, 08 Nov 2005 13:35:12 GMT
http://www.nytimes.com/2005/11/08/science/08flu.html?th&emc=th
Hazard in Hunt for New Flu: Looking for Bugs in All the Wrong Places
By GINA KOLATA
Published: November 8, 2005
Science moves in mysterious ways, and sometimes what seems like the end of
the story is really just the beginning. Or, at least, that is what some
researchers are thinking as they scratch their heads over the weird genetic
sequence of the 1918 flu virus.
Dr. Jeffery Taubenberger, a molecular pathologist at the Armed Forces
Institute of Technology who led the research team that reconstructed the
long-extinct virus, said that a few things seemed clear.
Specimens from 1918 yielded clues to today's virus.
The 1918 virus appears to be a bird flu virus. But if it is from a bird, it
is not a bird anyone has studied before. It is not like the A(H5N1) strain
of bird flus in Asia, which has sickened at least 116 people, and killed 60.
It is not like the influenza viruses that infect fowl in North America.
Yet many researchers believe that the 1918 virus, which caused the worst
infectious disease epidemic in human history, is a bird flu virus. And if
so, it is the only one that has ever been known to cause a human pandemic.
That, Dr. Taubenberger said, gives rise to a question. Are scientists
looking for the next pandemic flu virus in all the wrong places? Is there a
bird that no one ever thought about that harbors the next 1918-like flu? And
if so, what bird is it, and where does it live?
"I can't even assign a hemisphere," he said. "It just came from somewhere
else. Maybe it's in pigeons. Or in songbirds."
"It's weird, it's really weird," he added. "My view is to be undogmatic as
possible and just try to follow the data. This is the result we get. The
question is, What does it mean?"
Dr. Taubenberger's question emerged from the science fiction-like search for
the 1918 virus that eventually led to its reconstruction.
A decade ago, Dr. Taubenberger and his colleagues found shards of the
extinct virus in two fingernail-size snippets of formaldehyde-soaked lung
tissue from two soldiers and from the frozen lung of an Inuit woman who died
of the flu in 1918 and was buried in permafrost. Slowly and painstakingly,
they fished out the tiny fragments of viral genes and began reconstructing
them.
The first gene they sequenced was the one that codes for the hemagglutinin
protein on the virus's surface. Immediately, Dr. Taubenberger and his
colleagues were struck by an oddity: the chain of nucleotides that coded for
the amino acids in the protein were arranged differently from those found in
any other bird flu.
The genetic code is flexible; there is more than one way that a group of
three nucleotides can be arranged to code for the same amino acid. But every
bird flu virus ever studied used the same spellings for the hemagglutinin
amino acids. Not the 1918 flu.
There were two possibilities, Dr. Taubenberger thought. One was that bird
flus have evolved over the decades and that back in 1918, the amino acids in
bird viruses were simply coded differently.
Another was that if the 1918 flu virus came from a bird, it was no bird that
anyone had considered before.
"We decided there was no way to address this," Dr. Taubenberger said. After
all, the birds from 1918 were long gone, and their viruses had died with
them.
Then Dr. Thomas Fanning, a scientist in Dr. Taubenberger's group, mentioned
that he had a friend at the Smithsonian who worked at the National Museum of
Natural History in Washington. It had several thousand preserved birds from
the early 20th century that were floating in Mason jars of alcohol.
>From there, they reached James P. Dean, a supervisor in the division of
birds at the museum, who sent Dr. Taubenberger a computer printout of the
birds in the museum's collection - hundreds of birds, with notes telling the
species and the exact times and places where they were collected. But which
to choose?
Dr. Taubenberger consulted with one of the leading experts on bird flus,
Richard Slemons of Ohio State, who chose 40 birds on the museum's list, all
waterfowl collected around 1918. The museum found 25 of them.
The scientists took tiny pinches of tissue from passages of the birds'
excretory tracts, or cloacas, and Dr. Taubenberger looked for flu viruses in
the tissue. Six of the birds had a flu virus. The genetic coding for the
amino acids in those viruses was exactly like that in bird flu viruses
today, Dr. Taubenberger found.
In fact, the viruses had not even evolved. Human influenza viruses change
every year, mutating slightly so they can reinfect people who had just had
the flu and developed antibodies against it. But birds, Dr. Slemons said, do
not have much of an immune response to influenza, and so there is no
particular pressure for the virus to mutate.
Another reason the viruses stay the same, he said, is that some birds live
for only a couple of years and so, every year, the viruses have a new bird
population to infect. Finally, he said, birds are chronically infected with
lots of flu viruses at once, and all the viruses coexist peacefully.
"There are so many that there is no selective pressure on any virus," he
said.
But if bird viruses do not evolve and if the waterfowl viruses in 1915 and
1916 look just like bird viruses today, where did the 1918 virus come from?
Or was it really a bird virus?
After all, at the time that he looked at the Smithsonian birds, Dr.
Taubenberger had reconstructed only part of the virus's genetic sequence.
Maybe when he had the whole thing, the picture would change.
It did not. The entire sequence, published last month in Nature, had the
distinctive protein structures of a bird virus, he said. And it had that
same peculiar way of spelling its amino acids.
When he compared the 1918 virus with today's human flu viruses, Dr.
Taubenberger noticed that it had alterations in just 25 to 30 of the virus's
4,400 amino acids. Those few changes turned a bird virus into a killer than
could spread from person to person.
Dr. Taubenberger noticed that, so far, the A(H5N1) viruses in Asia have just
a few of those changes. They do not, however, have the unusual ways of
coding the amino acid instructions that the 1918 virus had. So are the Asian
bird viruses on their way to becoming pandemic viruses, or not?
Some experts like Dr. Peter Palese of the Mount Sinai School of Medicine in
New York say the A(H5N1) flu viruses are a false alarm. He notes that
studies of serum collected in 1992 from people in rural China indicated that
millions of people there had antibodies to the A(H5N1) strain.
That means they had been infected with an H5N1 bird virus and recovered,
apparently without incident.
Despite that, and the fact that those viruses have been circulating in China
more than a dozen years, almost no human-to-human spread has occurred. "The
virus has been around for more than a dozen years, but it hasn't jumped into
the human population," Dr. Palese said. "I don't think it has the capability
of doing it."
Dr. Taubenberger said he could argue it either way.
"It's a nasty virus," he said. "It is highly virulent in domestic birds and
wild birds. The fact that it has killed half the humans it has infected
makes it of concern, and the fact that it shares some features with the 1918
virus makes it of concern.
"But the fact that it has circulated in Asia for years and hasn't caused a
pandemic argues against it. Maybe there are some biological barriers we
don't understand."
So where will the next pandemic come from? Dr. Taubenberger says he wonders
if it may be from a bird no one has thought of, a bird with a flu virus that
has the same funny coding of amino acids that he saw in the 1918 flu.
He has teamed up with scientists in Alaska to get swabs from the cloacas of
migrating birds, and he is looking in those samples for flu viruses that
look like the one from 1918.
"Probably nobody else has thought much about this," Dr. Taubenberger said.
"But we've been staring at the sequence of the virus for the last 10 years,
and we've been thinking about it." For him, the story is not over; it has
just taken another turn.
.
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