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Scientists look for precursor of 1918 flu virus

KC

Moderator
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The reconstructed 1918 Spanish flu virus
</TD></TR></TBODY></TABLE>23 June 2006
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Researchers are trying to identify precursors to the 1918 'Spanish flu' virus that is thought to have killed some 40 million people.

The research could help explain how different types of flu virus succeed each other.

Led by Jeffery Taubenberger of the US Armed Forces Institute of Pathology in Washington DC and John Oxford of the UK-based University of London, the team is using a number of tissue samples collected as early as 1905 and stored in the cellars of the Royal London Hospital.

So far, the team has found 200 samples from people who may have died from flu, and confirmed five. Taubenberger says that all the confirmed cases were infected with an H3 strain of flu virus.

This describes the haemagglutinin protein on the surface of the virus's shell ? a key protein and important tool in identifying flu viruses. The team plans to sequence the entire viral genome and compare it to the H1N1 virus strain that caused the 1918 pandemic.

This could help them to understand the origins of the deadly 1918 virus.
Oxford says it could confirm or deny Taubenberger's contested theory that the virus jumped directly from birds to humans without combining its genes with those of a human virus.

Taubenberger made international headlines last year by resurrecting the 1918 flu virus.
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Re: Scientists look for precursor of 1918 flu virus

In laymans terms, correct me if I am wrong.

They are trying to find out which flu was replaced by H1N1 also to find out what other flus may have contributed to H1Ni's virulence.
 
Re: Scientists look for precursor of 1918 flu virus

Great find I think you are correct. It is a worthwhile effort.
 
Re: Scientists look for precursor of 1918 flu virus

when they confirmed H3, doesn't that mean that they
must have some partial H3-sequences from before 1918,
which they are keeping secret ?

That would be very important to know, which H3 and
whether it relates to current avian sequences from Alaska
or equine H3N8 or human H3N2.
It would give clues, how H1N1 replaced H3 in 1918, whether
there were reassortments before 1918, why there were
different waves in 1918 and (more or less) cross-imunity.
 
Re: Scientists look for precursor of 1918 flu virus

Why don't you follow the links from the original article?

http://www.sciencemag.org/cgi/content/full/312/5781/1725?ijkey=EUQIrNtTIuGnU&keytype=ref&siteid=sci

It'll get you to this page, which tells you that they have a couple of snippets up to 80bp long, sufficient to show that the virus circulating in ~1905 was very likely H3, but no further information. At this point it's simply confirmation of some early serological work from the 50s and 60s.
 
Re: Scientists look for precursor of 1918 flu virus

Why don't you follow the links from the original article?

............they have a couple of snippets up to 80bp long, sufficient to show that the virus circulating in ~1905 was very likely H3, but no further information. At this point it's simply confirmation of some early serological work from the 50s and 60s.

Since the article requires a paid subscription, that is difficult.

Is that 1905 snippet human, or is it related to:
AAM19233 326 Avian HA H7 Italy 1902 Influenza A virus (A/chicken/Brescia/440b/1902(H7))

.
 
Re: Scientists look for precursor of 1918 flu virus

Since the article requires a paid subscription, that is difficult.

The original post links to this page:
http://www.scidev.net/en/sub-suhara...sts-look-for-precursor-of-1918-flu-virus.html
(no subscription required)

That then links on to this page:
http://www.sciencemag.org/cgi/content/full/312/5781/1725?ijkey=EUQIrNtTIuGnU&keytype=ref&siteid=sci
This second page asks me for subscription data in IE, but not in Firefox. I don't think it's a cookie issue since my wife can also get access using Firefox, but I may be wrong.

It's a very short article just mentioning the existence of preliminary data. I don't want to quote the entire thing for copyright reasons, however there are only two relevant paragraphs. The first deals with prior seroarchaeology data:

In the 1950s and 1960s, a handful of researchers tested for hemagglutinin antibodies in people born before the 1918 pandemic. They proposed that an H2 strain swept the world during a pandemic in 1889, and H3 was introduced in another pandemic in 1900. A 1999 review of those same data concluded that H3 was more likely to have struck in the 1889 pandemic but warned that "seroarchaeology is not an exact science."
(see link I gave to the open access 1999 review)

The second deals with finding sequences from archived tissue samples from the early 1990s.

a medical student, found more than 200 suspected flu victims. So far, Taubenberger's team at AFIP has analyzed the lung tissue of only 12 of them, five of whom were confirmed to have had flu. And in four of those, sequencing of RNA snippets from the hemagglutinin gene--80 base pairs is the maximum length in these ancient samples--shows "it's absolutely an H3," Taubenberger says.

There's no conspiracy and no significant withheld data, just a very preliminary molecular confirmation of what was already known from serum studies.
 
Re: Scientists look for precursor of 1918 flu virus

Interesting paper. Thanks.

I did a quick read and had 2 immediate thoughts:

1) can they be sure the antibodies came from a human virus & not people's "backyard flocks"?

2) given that 1918 survivors still have antibody levels about 1000 times normal, I assume that antibody levels are not one of their factors, but rather the actual antibody.

Seroarchaeology sounds very interesting - I'll print out that paper and given it a few rereads.

Can the same seroarchaeology investigative methods be used to find out why so many older people aren't getting this new flu? Although, as someone posted today, that age group has the highest CFR. After reading about the slightly later incidence of elderly deaths in 1918 and 1957, I'll be watching to see if something similar happens this time.

.
 
Re: Scientists look for precursor of 1918 flu virus

Thanks. I reached the article through your first link.

http://www.sciencemag.org/cgi/content/full/312/5781/1725?ijkey=EUQIrNtTIuGnU&keytype=ref&siteid=sci
(a 2006 article)
last 2 paragraphs:

Only patient samples can yield solid answers, Taubenberger says. To find them, he teamed up with John Oxford of Queen Mary's School of Medicine at the University of London to explore a massive set of samples collected as early as 1905 and stored, along with patient records, in dusty cellars at the Royal London Hospital. Joanna Whitson, a medical student, found more than 200 suspected flu victims. So far, Taubenberger's team at AFIP has analyzed the lung tissue of only 12 of them, five of whom were confirmed to have had flu. And in four of those, sequencing of RNA snippets from the hemagglutinin gene--80 base pairs is the maximum length in these ancient samples--shows "it's absolutely an H3," Taubenberger says.

The team plans to spend the next several years sequencing the entire viral genome. If viruses from before 1918 are completely different than the pandemic virus, that would support Taubenberger's contested theory that the pandemic virus jumped directly from an avian host into the human population, says virologist Albert Osterhaus of Erasmus University in Rotterdam, the Netherlands. "This could be the clincher," says Oxford.

I don't understand why that finding would support a jump from birds, but not swine. Or are they excluding a pandemic from a previously circulating H1?

.
 
Re: Scientists look for precursor of 1918 flu virus

I'll check more closely later ...

so, Dowdle claims 1889 was H3 (presumably H3N8) but not 1900.

However Taubenberger claims H3 was present after 1900

these 80bp long snippets would be very useful.
They should demonstrate the ancestry of equine H3N8
from 1963 and later and the H3 found 2005-2007 in Alaska

it would be interesting to find the common ancestry date of
horses and human and avian flu so to see whether
and how long horse,human,avian flu did mix before 1918

why are these 80bp snippets being kept secret ?
Now we are facing another pandemic with some similarities
to 1918 and the concern is that we might get a 2nd virulent
wave as in 1918 ! Shouldn't the data be made available now ?
 
Re: Scientists look for precursor of 1918 flu virus

there are also swine with the equine H3N8 virus, BTW.

A/Swine/Chibi/01/2005/12/15(H3N8)
A/Swine/Anhui/01/2006/01/06(H3N8)

equine H3N8 segments 1,7,8 are close to 1918(H1N1)
so are segments 1,5,7 of Alaska/2005(H3N8)


where had that duck
A/Duck/LA/17G/1987(H3N8)
been ? LA=Louisiana ?
That virus was uploaded ~late 2008, I started a thread about it, it is
not similar to known viruses, a new lineage.
Maybe related to human H3N8 bfore 1918.

segment 1 has particularly high AT-score suggesting that
it may have evolved in mammals for decades/centuries.
Any mammal, what that duck may have got it from
and where flu evolves undetectedly since centuries ?
 
Re: Scientists look for precursor of 1918 flu virus

They should demonstrate the ancestry of equine H3N8
from 1963 and later and the H3 found 2005-2007 in Alaska

Why only equine>1963 and avian in about 2006?

Why not also the canine and swine H3N8?

.
 
Re: Scientists look for precursor of 1918 flu virus

Also, wouldn't you want to look at all H3s? - the avians have all nine Ns!

.
 
Re: Scientists look for precursor of 1918 flu virus

I've looked at those related to 1918. and i.e. segment 1

Canine,swine H3N8 descend from eqine 1963, nothing new there.

The Alaska birds are close to 1918, i.e. in segments 1,7,8.
So close, that I speculate flu may transmit in inner Alaska
by water and staying in the environment without replicating
for prolonged times
 
Re: Scientists look for precursor of 1918 flu virus

gsgs:

Just to add something interesting - here's a 1991 paper about precursors to 1918, where they speculate that swine and human flu came from a common source, then diverged about 1905:

http://www.springerlink.com/content/m85l477368h71466/fulltext.pdf

.


I haven't yet looked at synonymous vs.nonsynonymous mutations.
I just throw them all in one basket and I assume that's suitable -
except maybe for HA and to a lower degree NA.
They only examine HA and what they find in that paper ,
1906 orgine is only for HA. But presumably there were reassortments...

best avian match for spaflu BTW in HA is Anas/Crecca/Spain/2007 ,
just uploaded a few weeks ago

common ancestor ~1880-1900
 
Re: Scientists look for precursor of 1918 flu virus

Since the article requires a paid subscription, that is difficult.

Is that 1905 snippet human, or is it related to:
AAM19233 326 Avian HA H7 Italy 1902 Influenza A virus (A/chicken/Brescia/440b/1902(H7))

.

not related.
I doubt that 1902 sequences anyway because they are so similar
to Dobson/27
 
Re: Scientists look for precursor of 1918 flu virus

> Anas/Crecca/Spain/2007 ,

any of her ancestors after 1880 should be a better match to 1918 H1
where did they hide where did that Crecca get it from



---------------edit best known neighbors as of 2014 :-------------
Code:
  >A/Brevig Mission/1/1918,1918/10/10,USA,H1N1,Human

 929  212 2280 >KF435062,A/duck/Manitoba/1953,1953//,Canada,H10N7,Avian,1
 729  166 2274 >KF435047,A/duck/Manitoba/1953,1953//,Canada,H10N7,Avian,2
 776  167 2151 >CY004479,A/pintail duck/ALB/219/1977,1977/09/03,Canada,H1N1,Avian,3
1546  263 1701 >CY181369,A/greenwinged teal/Wisconsin/585/1983,1983//,USA,H1N1,Avian,4
1082  162 1497 >CY015446,A/black duck/Ohio/95/1993,1993/10/15,USA,H1N1,Avian,5
 848  114 1344 >CY015048,A/chicken/Rostock/45/1934,1934//,Germany,H7N1,Avian,6
 417   41  982 >CY132002,A/mallard/Ohio/11OS2045/2011,2011/08/17,USA,mixed,Avian,7
 357   30  838 >CY014661,A/turkey/Ontario/6118/1968,1968//,Canada,H8N4,Avian,8
 
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