July San Paolo Sequence Released

[AlaskaDenise]

Re: July San Paolo Sequence Released

Regarding HA/252, WHO published:

CHARACTERISTICS OF HUMAN INFLUENZA A H1N1, A H3N2 AND B
VIRUSES ISOLATED OCTOBER 2004 TO JANUARY 2005

Which makes clear the postion HA/252 is a significant change for many strains listed. It is the defining change for some of the new strains.

Read the charts and trees. It is not a "curious coincidence" according to WHO.

.

[gsgs]

Re: July San Paolo Sequence Released

I do not expect more sequences with that mutation.
I do see no connection to 1918 here.
We had other fatal cases without that mutation, why now ?
If just one single mutation were advantageous for the
virus, we would have already seen it long ago.
I think most of the common mutations are happening per infection

[gsgs]

Re: July San Paolo Sequence Released

AD, they talk about Y252F, are you sure they use the same numbering ?

Also V252M in flu-B which looks like a strange coincidence to me
and presumably unrelated

[HenryN]

Re: July San Paolo Sequence Released

I do not expect more sequences with that mutation.
I do see no connection to 1918 here.
We had other fatal cases without that mutation, why now ?
If just one single mutation were advantageous for the
virus, we would have already seen it long ago.
I think most of the common mutations are happening per infection

Please. This isn't Kansas (and the presence of 2 or the 3 polymorphisms in HK swine is NOT a coincidence).

[HenryN]

Re: July San Paolo Sequence Released

Regarding HA/252, WHO published:

CHARACTERISTICS OF HUMAN INFLUENZA A H1N1, A H3N2 AND B
VIRUSES ISOLATED OCTOBER 2004 TO JANUARY 2005

Which makes clear the postion HA/252 is a significant change for many strains listed. It is the defining change for some of the new strains.

Read the charts and trees. It is not a "curious coincidence" according to WHO.

.

As mentioned previously, V252M in influenza A using H3 numbering is NOT V252M using influenza B numbering,

[gsgs]

Re: July San Paolo Sequence Released

what exactly do you claim here ? What sequences did recombine
and how is 1918 involved ?
The mutation happened early last Century.


1918 and human H1N1 until now have ATA.
Early swine and swine-H1N1 until now -including ****** have GTG.
Now Sao Paulo/43812 has ATG.

What looks more likely GTG(******)-->ATG or ATA(human)-->swine-->ATG ?

[HenryN]

Re: July San Paolo Sequence Released

what exactly do you claim here ? What sequences did recombine
and how is 1918 involved ?
The mutation happened early last Century.


1918 and human H1N1 until now have ATA.
Early swine and swine-H1N1 until now -including ****** have GTG.
Now Sao Paulo/43812 has ATG.

What looks more likely GTG(******)-->ATG or ATA(human)-->swine-->ATG ?

The 2001 swine from Hong Kong has ATG. Polymorphisms are maintained in genetic reservoirs, and swine has many early polymorphisms (which are POORLY represented in the database), such as the A at the first position in the 252 codon (which is traced in the travel log).

Genes evolve (via recombination) at the GENETIC (nucleotide) level, not the gene product level.

[HenryN]

Re: July San Paolo Sequence Released

You understand very well. The V252M mutation that started this whole thread was stated clearly by Dr. Niman to be found in the 1918 virus. That is simply not true.

Please do not mispresent my posts. This thread was started to discuss changes in the Sao Paulo HA sequence from the first reported fatality in the Sao Paulo region, which had been made public minutes prior to the start of the thread. The polymorphism of most interest changed the first position of the 252 codon from a G to an A, which changed the 2009 pandemic protein position 252 from a V to an M, hence the name V252M.

The travel log listed a search of the entire flu database at Genbank for sequences that had an A at the first position, and also matched the upstream sequence in the Sao Paulo isolate. The number of sequences that were EXACT matches included the three 1918 HA sequences at Genbank which were in travel log in post #3 of the thread). Those sequences, as well as other human sequences, also had a change at the third position of the codon, so instead of encoding V252M, they encoded V252I (due to changes in the first and third position of the V252 codon).

I did NOT claim that V252M was in the 1918 sequence. When you said you didn't see a match (based on a survey of the gene PRODUCT) I looked at the 1918 sequence and posted that it had V252I because of an additional change.

I did not go into detail because those who have a genetic background could easily look at the 1918 sequences and see why the three sequences had V252I instead of V252M, and those who did not have a background would likely be confused by an explanation that did not included EXTENSIVE background, which today is taught at the middle school or high school level (but application of those lessons to real world data does not always translate).

[gsgs]

Re: July San Paolo Sequence Released

with so many swine sequences, it's not so surprising
that some has ATG

or was it that sequence discovered recently which matched
newflu in 7 segments ? ... I'll check...

[HenryN]

Re: July San Paolo Sequence Released

with so many swine sequences, it's not so surprising
that some has ATG

or was it that sequence discovered recently which matched
newflu in 7 segments ? ... I'll check...

Please. The match with the 2001 HK swine sequence was for 2 of the 3 changes in Sao Paulo.
The number of swine sequences in the database is VERY small.

[HenryN]

Re: July San Paolo Sequence Released

I do not expect more sequences with that mutation.
I do see no connection to 1918 here.
We had other fatal cases without that mutation, why now ?
If just one single mutation were advantageous for the
virus, we would have already seen it long ago.
I think most of the common mutations are happening per infection

V252M is NOT common. In fact, it is not in any of the pandemic sequences other than the fatal Sao Paulo case. It is also in the 2001 swine sequence from HK, which also has the third polymorphism in the Sao Paulo HA sequence.

Do you think that the presence of 2 of 3 Sao Paulo polymorphisms in the 2001 HK swine sequence is a "coincidence" and due to "random mutations"????????

[gsgs]

Re: July San Paolo Sequence Released

I have 4 changes of Sao Paulo/43812 to ******/index in HA:
G796A,G930T,A1281G,C1408T.
The 1st and 3rd are also in A/SW/HK/NS1659/2001(H1N1)
while the 2nd and 4th aren't.
NS1659 has 162 differences from ******/index in HA (coding region)

that's roughly a 30% chance (I estimate) to find a random mutation (wrt. **) in NS1659.
C(4,2)*.3^2*.7^2=0.26 to find 2 of the 4 mutations in NS1659 a priory.

[HenryN]

Re: July San Paolo Sequence Released

I have 4 changes of Sao Paulo/43812 to ******/index in HA:
G796A,G930T,A1281G,C1408T.
The 1st and 3rd are also in A/SW/HK/NS1659/2001(H1N1)
while the 2nd and 4th aren't.
NS1659 has 162 differences from ******/index in HA (coding region)

that's roughly a 30% chance (I estimate) to find a random mutation (wrt. **) in NS1659.
C(4,2)*.3^2*.7^2=0.26 to find 2 of the 4 mutations in NS1659 a priory.

Your "estimate" of finding two rare polymophisms in the same distantly related swine sequence is utter nonsense. The C1408T is quite common and not newly acquired. There are only three newly acquired polymorphisms and the two shared with the HK swine are VERY rare. Your "estimate" is even more absurd than your "20% estimate" that the 2009 pandemic was not a pandemic (after WHO had declared it a pandemic!).

[Snicklefritz]

Re: July San Paolo Sequence Released

Snicklefritz said:

But, I do have another question. Whether it's V252M or V252I, do we know how that affects the biology, the clinical picture for a patient? Or, is it just a curious coincidence that 'it', whatever 'it' is, was present in 1918, or in human H1N1?

The bold underlined portion was a question that I have not heard an answer to. Do we know if this change is clinically significant? The fact that the poor girl in Sao Paolo had this change, and died, does not mean her death was caused by this change. Thousands have already died that apparently did not have this change. Or, have I messed that up too?

I'm just looking for clarification. What does this change mean, beyond being evidence that this may be a 1918 rerun?

[wotan]

Re: July San Paolo Sequence Released

Snicklefritz said:



The bold underlined portion was a question that I have not heard an answer to. Do we know if this change is clinically significant? The fact that the poor girl in Sao Paolo had this change, and died, does not mean her death was caused by this change. Thousands have already died that apparently did not have this change. Or, have I messed that up too?

I'm just looking for clarification. What does this change mean, beyond being evidence that this may be a 1918 rerun?

I've tried to find information but have had no luck. I think there is a distinct possibility that the answer is we simply don't know.