Don't Blame Birds for 1918 Flu

[KC]

Re: Don't Blame Birds for 1918 Flu

So,

It could be possible that both a novel H1N1 virus (swine) and a novel H5N1 (avian) virus are circulating around the globe, and the common mixing vessels (swine or humans) are contributing to re-assortment and/or recombination? At the same time, normal seasonal influenza was/is also spreading.

Influenza is influenza.... it evolves... sometimes rapidly regardless of where the final pandemic origin spreads from.

My big question... and I've asked it many times here before and been shunned.... What might the effects of other endemic or epidemic non-influenza viruses that have similar structures have in the equation?

Could co-infections between an influenza virus and a non-influenza virus cause a problem if they share similar molecular traits?

[AlaskaDenise]

Re: Don't Blame Birds for 1918 Flu

......mRNA's are often expressed on the surface of a cell. If a cell is infected with a virus it will express those mRNAs. If the mRNAs look similar to host sequences (ie. similar codon usage to that of the host) then the host will not recognize the infection...........

That was a great explanation of the increased mutation rate.

In thinking about this more, now I'm a little confused.

In "If a cell is infected with a virus it will express those mRNAs." - is "it" the new virons that will now have the host mRNAs on their (viron) surfaces?

Assuming the answer is yes, then....

In "If the mRNAs look similar to host sequences ..... then the host will not recognize the infection" - if the "baby" virons are disguished (using mRNA) to look like the host so they can escape detection, how does the immune system ever fight them off? (When I asked my self this question, I realized I might have misunderstood the explanation, hence this question)

.

[gsgs]

Re: Don't Blame Birds for 1918 Flu

they (edit---the mRNAs) look just a tiny bit different, giving a slighly increased
probability to survive - the process goes over decades.

But nucleotides are not recognized by the immune system
as I understand, only amino-acids.
Nor are they expressed on the cell-surface (?)

mammalean flu acquires more A,T nucleotides over the
years,decades,centuries - but this is presumably another process


epitopes in the cell are transported to the surface, so the killer cells
can see which cells to kill

[HenryN]

Re: Don't Blame Birds for 1918 Flu

they look just a tiny bit different, giving a slighly increased
probability to survive - the process goes over decades.

But nucleotides are not recognized by the immune system
as I understand, only amino-acids.
Nor are they expressed on the cell-surface (?)

mammalean flu acquires more A,T nucleotides over the
years,decades,centuries - but this is presumably another process


epitopes in the cell are transported to the surface, so the killer cells
can see which cells to kill

Interferon

[gsgs]

Re: Don't Blame Birds for 1918 Flu

Brevig/1918 is more distant in PB2 to all other early human H1N1 than in PB1 or PA.
This indicates that it is not the ancestor of all these but rather
a reassortant.
But the same is true for Wilson-Smith/1933 , so there should be other reasons

Hickox/1940 seems to be from ~1945 rather than from 1940
Swine/Jamesburg/1942 seems to be from ~1932 rather than 1942

-----edit-------------
otoh, this (more mutations in PB2) is not seen in the swine linage
but the swine segments don't show any similarity with the human ones,
so there probably was no mixing human-swine after 1918

where should this new PB2 have come from ?

[AlaskaDenise]

Re: Don't Blame Birds for 1918 Flu

they ........

??? What is the "they"?

What post are you referencing?

.

[Emily]

Re: Don't Blame Birds for 1918 Flu

So,

It could be possible that both a novel H1N1 virus (swine) and a novel H5N1 (avian) virus are circulating around the globe, and the common mixing vessels (swine or humans) are contributing to re-assortment and/or recombination? At the same time, normal seasonal influenza was/is also spreading.

Influenza is influenza.... it evolves... sometimes rapidly regardless of where the final pandemic origin spreads from.

My big question... and I've asked it many times here before and been shunned.... What might the effects of other endemic or epidemic non-influenza viruses that have similar structures have in the equation?

Could co-infections between an influenza virus and a non-influenza virus cause a problem if they share similar molecular traits?

Is this along the lines of what you are wondering about?

http://pathmicro.med.sc.edu/mhunt/genet.htm

"Recombination enables a virus to pick up genetic information from viruses of the same type and occasionally from unrelated viruses or even the host genome

[kiwibird]

Re: Don't Blame Birds for 1918 Flu

Really interesting Emily. Is this part of the answer to KC's question?

[gsgs]

Re: Don't Blame Birds for 1918 Flu

> seasonal and classic swine H1N1 viruses were not derived directly
> from BM/1918, but their precursors co-circulated during the pandemic.

> the 1918 H1N1 pandemic virus most likely was generated by
> reassortment between mammalian viruses and a previous human
> strain and was not a pure avian virus.

then it would have been much different and we would see it in BM/18

> the BM/1918 virus H1, N1, PB1, PA, and NP genes clustered with human
> H1N1 influenza A viruses, whereas its PB2, M, and NS genes
> clustered with swine.

differences in promille in the 8 segments:
BM/18-WS/33 : 48,32,37,81,42,68,27,29
BM/18-SW/31: 44,46,51,65,44,51,39,45

so I'd say there were more mutations in humans in HA and NA (because of immunity)
and more mutations in swine in the other 6 segments

> TMRCA:1903,1914,1914,1916,1909,1913,1896?,1908

reassortments are rare, so multiple reassortments in different years are even rarer

AT-score in the 8 segments: (the longer in mammals, the higher the score)

BM/18:5568,5665,5620,5614,5310,5751,5152,5465
WS/33:5621,5772,5720,5878,5354,5630,5340,5563
Ma/54:5740,5856,5784,5791,5368,5848,5266,5622
Sw/57:5620,5772,5754,5942,5456,5874,5246,5649

> (Table 1) suggest those genes (1,5,8)
> have circulated in humans since the 1889 H3 influenza pandemic

H3N8 ? The same virus which is still in horses,dogs. That virusis rare in birds,
did it go from birds to humans in 1889 in all segments ?
Still 19 years to gain in AT-score, which apparantly hasn't happened (?)

> However, our results suggest that the same NP gene lineage has
> been circulating in human influenza A viruses since the 19th
> century, consistent with the report by Gammelin et al. (19). [from 1990]


> Taken together, our results indicate that it is unlikely that the
> BM/1918 virus could have resulted from adaptation of an entire
> avian virus introduced directly into humans shortly before the
> pandemic. More likely, it was generated by reassortment between
> previously circulating swine and human strains and introduced
> avian viruses over a period of years.


> Phylogenetic relationships between BM/1918 and classic swine
> H1N1 virus PB2, M, and NS genes also indicate that classic swine
> H1N1 is a reassortant between BM/1918 and an unknown virus.

which segments from BM/1918 ?

> As such, classic swine H1N1 is derived partially from BM/1918
> and is not a precursor of the 1918 pandemic virus (Fig. 1 and
> Figs. S1–S8) (9).


I don't believe it (yet).
I haven't looked at the phylo-graphs or the 1957,1968 data yet.
But this looks even more doubtful to me, that 1957,1968
should have been created years ago

http://www.setbb.com/fluwiki2/viewtopic.php?p=1229

[super_flu]

Re: Don't Blame Birds for 1918 Flu

That was a great explanation of the increased mutation rate.

In thinking about this more, now I'm a little confused.

In "If a cell is infected with a virus it will express those mRNAs." - is "it" the new virons that will now have the host mRNAs on their (viron) surfaces?

Assuming the answer is yes, then....

In "If the mRNAs look similar to host sequences ..... then the host will not recognize the infection" - if the "baby" virons are disguished (using mRNA) to look like the host so they can escape detection, how does the immune system ever fight them off? (When I asked my self this question, I realized I might have misunderstood the explanation, hence this question)

.

The answer is no.

The host cell will express mRNAs on its surface. Regardless of whether viral or not. It's a mechanism for host cells to monitor its cells are behaving correctly. During infection viral genetic material and proteins are produced at high levels. Some of these RNAs are placed on the surface of the host cell. Other cells may recognize these RNAs as not self and kill the cell. If viruses accumulate mutations to account for codon usage bias this will make the viral genome appear more like its host. This does not necessarily result in new phenotypes. In other words, these are silent mutations that do not result in new amino acids. They just use codes for the same amino acid that are similar to the host species.

[super_flu]

Re: Don't Blame Birds for 1918 Flu

they (edit---the mRNAs) look just a tiny bit different, giving a slighly increased
probability to survive - the process goes over decades.

But nucleotides are not recognized by the immune system
as I understand, only amino-acids.
Nor are they expressed on the cell-surface (?)

mammalean flu acquires more A,T nucleotides over the
years,decades,centuries - but this is presumably another process


epitopes in the cell are transported to the surface, so the killer cells
can see which cells to kill

The process can happen much much much faster than decades. RNA viruses are amongst the fastest evolving genetic populations known. These mutations may accumulate in relatively few replication cycles.

If swine hosts have a similar codon usage bias as humans, yet with shorter life spans and relatively few symptoms from influenza infection it suggests that these hosts would be perfect to mediate mammalian adaptation. Add human handlers for frequent close contact and increased probability of interspecies transmissions

[super_flu]

Re: Don't Blame Birds for 1918 Flu

>


I don't believe it (yet).
I haven't looked at the phylo-graphs or the 1957,1968 data yet.
But this looks even more doubtful to me, that 1957,1968
should have been created years ago

I'm surprised you're skeptical. Especially considering we're all concerned about a novel virus that has taken as long as 30 years (the M and Na genes were introduced into Eurasian swine in 1979) for all the viral segments to be in the correct host at the same time to emerge and cause our current pandemic.

[gsgs]

Re: Don't Blame Birds for 1918 Flu

if some early H1N1 X in some segment was not derived directly from BM/18,
then there should have been avian viruses which are closer to that virus X
in that segment than to BM/18.
Or should at least have unusually many mutations which coincide with
X in the positions where X differs with BM/18.

Some such avian viruses should still be around or should have been isolated
in the years since 1918.

But I found none. (except some turkeys which obviously caught a recent
swine virus)


-------------edit--------------
sorry, this is not true what I said , I made a thought error.
If there was just one introduction from birds
to humans in -say- 1903 and then it developed independently
to BM/18 and WS/33, then all birds should be more distant from
WS/33 than from BM/18.
But the time of the introduction may be estimated from these
differences

[super_flu]

Re: Don't Blame Birds for 1918 Flu

if some early H1N1 X in some segment was not derived directly from BM/18,
then there should have been avian viruses which are closer to that virus X
in that segment than to BM/18.
Or should at least have unusually many mutations which coincide with
X in the positions where X differs with BM/18.

Some such avian viruses should still be around or should have been isolated
in the years since 1918.

But I found none. (except some turkeys which obviously caught a recent
swine virus)

There's no reason to suspect that further reassortment happened with avian viruses. In fact, currently we have a pandemic H1N1 virus which is antigenically similar to a seasonal H1N1 virus but contains gene segments most closely related to another seasonal subtype H3N2. All three of these viruses currently co-circulate in humans. There is no reason to suspect that further reassortment will can not happen with these viruses. In fact this is a major worry that researchers are monitoring (as well as a million other worries). Who knows what will be circulating in 30 years and how they'll be related to say California/04/2009

The phylogenies and date estimates, however, do suggest that prior to the emergence of the 1918 virus their was reassortment and the gene segments may not have been introduced as a single intact particle.

This might be the best idea we get of how the 1918 virus was generated. I suspect that ideas surrounding the generation of the 1918 virus will always be contentious.

BM/1918 is only one virus in a population and there is no reason to suspect that this was typical of those circulating. The search for this virus did not look to sample the diversity of viruses circulating at that time, but rather to search for the most lethal example. In Brevig Mission I believe the virus was extremely fatal and all but three people died (my memory might be wrong on the number of survivors).

[gsgs]

Re: Don't Blame Birds for 1918 Flu

wherever it (1918 panflu) had come from, originally it was in birds, as all flu-A.
Whether it went into mammals 1918 or 1890, doesn't matter so much.(---edit--- for this analysis)
There should still be some bird-sequence showing it, being closer to
~1930s-sequences than to BM/18. (if that 1930s sequences did not
directly come from BM/18 as the paper suggests)

BM/18 is not so unique. We have 3 viruses from 1918 and one from 1919.
Partial sequences only, but they coincide with BM/18.

You suggest the pandemic strain had died and some unnoticed
seasonal strain did take over ? Any example that this ever happened ?

Local differences of the strain are presumably small, as was seen in other pandemics.
H3N2 did reassort a couple of times with segments from old H2N2 between 1968-1972,
though. But not many differences in the single segments.


---------edit--------
sorry, I made a mistake, see my post above