Don't Blame Birds for 1918 Flu

[gsgs]

Re: Don't Blame Birds for 1918 Flu

suppose we had no sequences from before 1929.
How close could we come to estimate 1918 ?

we could just take the closest few human and swine sequences
and form their average.
5 human + 5 swine --> the average has 525 differences to BM18

if we add 6118 ---> 408=62+46+59+99+45+73+17+7 differences (~10 years uncertainety)


SW31 has 643 differences to BM18, WS33 590, Jamesburg/42 635

 

[pjie2]

Re: Don't Blame Birds for 1918 Flu

the sequences before 1918 were almost withdrawn, Taubenberger
said it was probably contamination

Another possible explanation, of course. C'est la vie.

It's interesting that there are two subclades of bird flu sequences in that figure - one containing the North American strains, and the other containing European / Asian strains. Furthermore, the goose 1917 sequence falls solidly within the NA group rather than the European / Asian group. This indicates one of two things:

1) The two bird subclades split some time before 1917, and the goose sequence genuinely does happen to come from one rather than the other. In which case there were presumably other H1N? bird flus circulating in 1917 which fell into the European / Asian subclade, but these have not been sampled.

2) The 1917 goose sequence is actually a contaminant from a more recent NA bird flu strain.


Also, the branch lengths between the various avian sequences, which span the time from 1976 to 1990, i.e. 14 years, are longer than the branch linking the two subclades. If the 1917 goose sequence isn't a recent contaminant, you have to postulate that the NA and European/Asian clades separated some time before 1917, stayed almost unchanged for several decades, and then started changing more rapidly some time in the 1970s when we started surveying them.

It would be interesting to look for preserved bird flus in samples from the intervening time period - these would help resolve the issue.

 

[HenryN]

Re: Don't Blame Birds for 1918 Flu

I knew I shouldn't have mentioned H7N9. I was only using it to illustrate the flaw in the logic.

From that tree we see that yes, there was an avian H1N? strain circulating in Brevig in 1917 whose H sequence is more similar to current avian H1N1 than to 1918 pandemic H1N1. We can therefore rule out Brevig 1917 as the ancestor of the H segment of the 1918 pandemic virus. I still don't see how you can conclusively rule out avian ancestry without a much more comprehensive survey of 1917 bird sequences. There may have been more than one H1N? bird flu in circulation in 1917. You're extrapolating a single 1917 sequence to claim that no 1917 bird flu could be the ancestor of the 1918 pandemic.

I'm not of course claiming avian ancestry for it - as I said I'm agnostic on the issue. I just don't think the data are conclusive.

No. The 1917 sequence fits the pattern. Avian H1 is VERY different from mammalian H1, and 1918 is clearly mammalian H1. The tree pictured is for H1. The same relationship is found for the other 7 gene segments (PB2, PB1, PA, NP, NA, MP, NS) so there are 8 phylogenetic tress, all showing 1918 to be mammalian H1N1 and related to WSN/33 human H1N1 and swine/Iowa/15/1930 swine H1N1.

 

[HenryN]

Re: Don't Blame Birds for 1918 Flu

Another possible explanation, of course. C'est la vie.



2) The Brevig sequence is actually a contaminant from a more recent NA strain.

There are MULTIPLE 1918 sequences. The first tree I showed had 3 (South Carolina, Alaska, New York), which were IDENTICAL.

http://jvi.asm.org/cgi/content-nw/full/76/15/7860/F1

The lab error nonsense gets VERY old very quickly, especially when there is ZERO data to support the SPECULATION. The 1918 sequence is quite distinct. 1918 sequences were from Alaska, London, South Carolonia, New York, and maybe more.

The only contamination is this thread littered with nonsense posts by those who OBVIOUSLY have NOT looked at the data.

Here are some clues:
The viruses are named after the originating location
NY = New York
SC = South Carolina
Brevig = Brevig Mission in Alaska

 

[gsgs]

Re: Don't Blame Birds for 1918 Flu

Brevig Mission is from 1918, not 1917

everyone exept niman thinks it's avian, AFAIK



it may have been in mammals for a few years before 1918, as the paper
claims - but not decades

 

[pjie2]

Re: Don't Blame Birds for 1918 Flu

Please. There are MULTIPLE 1918 sequences. The first tree I showed had 3 (South Carolina, Alaska, New York), which were IDENTICAL.

http://jvi.asm.org/cgi/content-nw/full/76/15/7860/F1

The lab error nonsense gets VERY old very quickly, especially when there is ZERO data to support the SPECULATION. The 1918 sequence is quite distinct. 1918 sequences were from Alaska, London, South Carolonia, New York, and maybe more.

The only contamination is this thread littered with nonsense posts by those who OBVIOUSLY have NOT looked at the data.

Here are some clues:
The viruses are named after the originating location
NY = New York
SC = South Carolina
Brevig = Brevig Mission in Alaska

As should have been clear from the context of the post, I meant that there was a possiblity that the 1917 goose sequence was a contaminant from a more recent NA bird flu strain. I have edited my post to correct my mis-naming of the sequence.

 

[HenryN]

Re: Don't Blame Birds for 1918 Flu

Brevig Mission is from 1918, not 1917

everyone exept niman thinks it's avian, AFAIK



it may have been in mammals for a few years before 1918, as the paper
claims - but not decades

The data couldn't be clearer (10 mammalian polymorphisms in 2005 Nature paper notwithstanding).

 

[HenryN]

Re: Don't Blame Birds for 1918 Flu

As should have been clear from the context of the post, I meant that there was a possiblity that the 1917 goose sequence was a contaminant from a more recent NA bird flu strain. I have edited my post to correct my mis-naming of the sequence.

As noted earier, the 1917 sequence is a MINOR datapoint. 1918 is mammalian with ZERO data pointing to avian.

 

[pjie2]

Re: Don't Blame Birds for 1918 Flu

As noted earier, the 1917 sequence is a MINOR datapoint. 1918 is mammalian with ZERO data pointing to avian.

If there's zero reliable avian or swine data from before 1918, then surely that's zero data pointing either way?

Yes, it's nice to see that the 1918 flu sits about half way between human and swine H1N1 sequences from the 1930s. This is exactly what you expect if both are ultimately descended from the 1918 flu, or from other similar co-circulating mammalian flus. Doesn't really tell you anything about what was going on in the couple of decades leading up to 1918.

As far as I can see, the identification of 1918 as non-avian in origin hinges on that 1917 goose sequence, although the recent paper may have more to say on the matter.

 

[HenryN]

Re: Don't Blame Birds for 1918 Flu

typo

Brevig Mission is from 1918, not 1917

everyone exept niman thinks it's avian, AFAIK



it may have been in mammals for a few years before 1918, as the paper
claims - but not decades

Hong Kong's PNAS paper said that THEY didn't think 1918 was avian - they thought it was swine / human. Kawaoka just published a Nature paper showing that 1918 survivors had antibodies that cross reacted with SWINE pandemic H1N1 (indicating 1918 H1N1 was SWINE).

Humans and swine are MAMMALS, which are EASILY distinguished from avian, as seen (by those who can read a phylogenetic tree) in phylogenetic trees for ALL 8 gene segments.

The only reason for the avian nonsense was the 2005 Nature paper. Sequences for the four internal genes were released, along with the bizarre analysis that claimed that avian flu need 10 changes to go pandemic, based on 1918 polymorphsims, but ALL 10 were MAMMALIAN polymorphism that not only were in 1918, but also in human H1N1 and swine H1N1.

One of those 10 changes was E627K, which produces optimal activity at 33C, instead of the avian version, which is optimal at 41 C (body temperature of a bird).

E627K is in ALL human influenza A (including 1918). It did NOT suddenly appear in 1916, 1917, or 1918. The HUMAN body temperature hasn't change recently, and humans have been infected by influenza for eons.

MAMMALIN influenza is NOT new and neither are the MAMMALIN markers found in MAMMALIAN 1918.

The 2005 Nature paper sequence was fine. The interpretation of the data was utter nonsense that was ONLY believable because it was published in Nature, and those who believed it couldn't read sequences, so they went with the peer reviewed publication, even though it was OBVIOUSlY false (to anyone who LOOKED at the DATA) the second it was published.

 

[HenryN]

Re: Don't Blame Birds for 1918 Flu

As far as I can see, the identification of 1918 as non-avian in origin hinges on that 1917 goose sequence, although the recent paper may have more to say on the matter.

Influenza did NOT begin infecting humans in 1918.

Mammalian and avian differences are not new and did NOT suddenly appear in 1918!

 

[Solarpanel]

Re: Don't Blame Birds for 1918 Flu

Good Doctor

Since you have spend a long time studing these virus, what are chances that the H5N1 and the H1N1 will mix to form a more dangerous virus? High, moderate, low?

 

[HenryN]

Re: Don't Blame Birds for 1918 Flu

Good Doctor

Since you have spend a long time studing these virus, what are chances that the H5N1 and the H1N1 will mix to form a more dangerous virus? High, moderate, low?

To mix they have to be in the same host, so swine H1N1 movement into humans doesn't necessarily increse that liklihood. In fact H5N1 seems to find swine H1N1 in swine on a fairly regular bases. The H's are still different serotypes, but the N's could mix more easily, because they are both N1's. The same is true for the internal genes, However, I expect more exchanges between swine and human H1N1's becasue they are the same serotype and now infect the same host, so I think there will be multiple exchanges.
However, big changes can happen because of small exchanges, so putting swine H1N1 into a new host opens the door for new possiblities,
The new sequences are being monitored VERY closely.

 

[gjs47]

Re: Don't Blame Birds for 1918 Flu

What is the trigger or recombination we should be watching for to know when the worst case scenario has become reality? Thank you.

 

[Mamabird]

Re: Don't Blame Birds for 1918 Flu

To mix they have to be in the same host, so swine H1N1 movement into humans doesn't necessarily increse that liklihood. In fact H5N1 seems to find swine H1N1 in swine on a fairly regular bases. The H's are still different serotypes, but the N's could mix more easily, because they are both N1's. The same is true for the internal genes, However, I expect more exchanges between swine and human H1N1's becasue they are the same serotype and now infect the same host, so I think there will be multiple exchanges.
However, big changes can happen because of small exchanges, so putting swine H1N1 into a new host opens the door for new possiblities,
The new sequences are being monitored VERY closely.

Yes, and perhaps a good example is the S224P change in the PA segment of particular pandemic H1N1 Swine Flu vuruses. Almost all the matches in existing data bases are H5N1 infections. While folks may worry that Bird Flu viruses will mix with Swine Flu viruses, I suspect they already have to some extent.

 

[HenryN]

Re: Don't Blame Birds for 1918 Flu

Yes, and perhaps a good example is the S224P change in the PA segment of particular pandemic H1N1 Swine Flu vuruses. Almost all the matches in existing data bases are H5N1 infections. While folks may worry that Bird Flu viruses will mix with Swine Flu viruses, I suspect they already have to some extent.

Yes, when I initially began looking at H5N1 polymorphisms that were from patients in Vietnam and Thailand in 2004, I kept finding swine polymorphisms. On occasion H9N2 was thrown in, but these were mostly internal genes and H5N1 and H9N2 are very similar. Swine and H9N2 have had a relationship for some time, and H5N1 joins also (but this is more swine / wild bird interactions than human).
The viruses know how to get around and exchange bits and pieces of genetic info, regardless of whether the sequencers do or don't understand.

 

[Mamabird]

Re: Don't Blame Birds for 1918 Flu

Yes, when I initailly began looking at H5N1 polymorphisms that were from patients in Vietnam and Thailand in 2004 I kept finding swine polymorphisms. On occasion H9N2 was thrown in, but these were mostly internal genes and H5N1 and H9N2 are very similar. Swine and H9N2 have had a relationship for some time, and H5N1 joins also (but this is more swine / wild bird inteactions than human).
The viruses know how to get around and exchange bits and pieces of genetic info, regardless of whether the sequencers do or don't understand.

Yep, and the exchange is not through reassortment either. Only small pieces of each segment affected.

 

[sharon sanders]

Re: Don't Blame Birds for 1918 Flu

Niman - no personal insults. Stop it.

 

[super_flu]

Re: Don't Blame Birds for 1918 Flu

Please. The phylogenetic analysis is VERY clear.
1918 is OBVIOUSLY mammalian.

This is not true. In fact, the original phylogenies published by Taubenberger and the subsequent phylogenetic analyses by numerous groups have shown that, for the PA and PB1 genes an avian lineage is in the basal position of the mammalian H1N1 lineage. This is also shown in the new paper. The new paper suggests reassortment was involved with the generation of this virus. Consistent with reassortment the emergence of the 1957, 1968 and the 2009 influenza pandemics. While the virus has circulated in a mammalian host prior to the outbreak the phylogenies do not support a single source for the 8 genetic precursors of this virus rather than being introduced in toto from an avian source.

 

[super_flu]

Re: Don't Blame Birds for 1918 Flu

Brevig Mission is from 1918, not 1917

everyone exept niman thinks it's avian, AFAIK



it may have been in mammals for a few years before 1918, as the paper
claims - but not decades

Actually, the paper suggests that this virus emerged as a reassortment between pre-existing mammalian influenza viruses and others introduced more recently, into an intermediate host.