A/Shanghai/71T/2009 acquired E627K

[gsgs]

Re: A/Shanghai/71T/2009 acquired E627K

the fact that we have possible reassortment and E627K
in the same virus together with the other 4 mutations
close to 627 in PB2 lets me assume that it's somehow
a lab error.
Or an immunodeficient patient.
Or extensive growth of viruses over several generations.

So many A-nucleotides
So many mutations in total, i.e. Shanghai/37T
Why the T in the name ?

we sometimes see such things with nearby mutations,
I tend to ignore them, they look like errors.


e.g. these Paris-isolates Paris/2590 , Paris/2592 ,...
1059,1062,1080,1317,1329,1330 in NA - what is it ?

Norway/1168,1177 156,159,162 in PB1

Italy/02 in NP

Mexico/47N in NA

Shanghai/37T in NA

[AlaskaDenise]

Re: A/Shanghai/71T/2009 acquired E627K

Why would an immunodeficient patient's infection have a different set of genes? (sources please)

.

[gsgs]

Re: A/Shanghai/71T/2009 acquired E627K

not different genes, but prolonged infection and more mutations.

Imagine one virus infecting a human, then after 2 days a mutation
occurs and spreads inside the human as well as the original virus.
After 4 days it transmits to another person, how likely is it that
that 2nd person gets the mutation ?
(answer:remote)
When you wait 2 weeks, however then the level of the original virus
and the mutated one in the body should be almost 50%:50%

several examples of immunodefient people with influenza here at FT,
I remember I once even sent you a link by PM

maybe I can search direct links later, if there is still demand...

[gsgs]

Re: A/Shanghai/71T/2009 acquired E627K

looking for 3d-images of PB2 and how the locations around 627 fold :

http://www.lightsources.org/images/pressreleases/2007/prembl072_1.jpg

http://www.biohealthbase.org/gsearch/posters/OptionsVIPoster.pdf

http://www.ebi.ac.uk/thornton-srv/databases/pdbsum/2jdq/traces.jpg

http://www.flutrackers.com/forum/showthread.php?t=58159

(can someone see those pictures with jmol ? - I can't)

[AlaskaDenise]

Re: A/Shanghai/71T/2009 acquired E627K

not different genes, but prolonged infection and more mutations.

Imagine one virus infecting a human, then after 2 days a mutation
occurs and spreads inside the human as well as the original virus.
After 4 days it transmits to another person, how likely is it that
that 2nd person gets the mutation ?
(answer:remote)
When you wait 2 weeks, however then the level of the original virus
and the mutated one in the body should be almost 50%:50%

several examples of immunodefient people with influenza here at FT,
I remember I once even sent you a link by PM

maybe I can search direct links later, if there is still demand...

So you're referring to Dr. Webster's "superspreader" outcome in H5N1-infected HIV patients? If so, now I understand what you mean. As I remember, there wasn't a firm conclusion.

.

[gsgs]

Re: A/Shanghai/71T/2009 acquired E627K

immunodeficient child with prolonged infection:

http://www.flutrackers.com/forum/showthread.php?t=13292

> It is likely to be practical to produce immunodeficient pigs since pigs can be bred and raised
> in germ-free environments (eg: Gnotobiotic pigs J Virol (1998) 72,:330-338).

these could be suitable to produce new dangerous flu-strains ?!
and may explain the many mutations and secrecy with the Alberta-pigs ?

------edit--------------------------
another source (although old) :

http://jvi.asm.org/cgi/reprint/65/5/2340

.0058-.017 mutations per nucleotide-position in HA per year (~.004 are normal)
.0035-.024 mutations per nucleotide position in NP per year (~.003 are normal)

[AlaskaDenise]

Re: A/Shanghai/71T/2009 acquired E627K

http://www.flutrackers.com/forum/showthread.php?t=13292

Yes, FT ancient history......good reading.

.

[HenryN]

Re: A/Shanghai/71T/2009 acquired E627K

<a rel="nofollow" href="http://www.recombinomics.com/News/06180901/H1N1_Swine_E627K.html">Commentary</a>

[AlaskaDenise]

Re: A/Shanghai/71T/2009 acquired E627K

<a rel="nofollow" href="http://www.recombinomics.com/News/06180901/H1N1_Swine_E627K.html">Commentary</a>

Commentary


E627K Acquisition in Swine H1N1 Raises Pandemic Concerns

Recombinomics Commentary 11:37
June 18, 2009

The recently released PB2 sequence from a patient in Shanghai (see <a rel="nofollow" href="http://flutracker.rhiza.com">Maps</a>) contains E627K. This is the first reported acquisition of this change, which is present in virtually all human influenza A isolates, including the pandemic strain from 1918.

The current isolate, A/Shanghai/71T/2009, was collected May 31, 2009 and the sequence was deposited at Genbank on June 10, 2009. The isolate is closely related to the swine H1N1 currently spreading worldwide, and all positions upstream from E627K match the consensus sequence, indicating the E627K was not acquired through reassortment with human PB2 or other H1N1 viruses that were not closely related to the swine H1N1 circulating in the human population.

Acquisition of E627K is a <a rel="nofollow" href="http://www.recombinomics.com/News/05120903/Swine_H1N1_Seasonal.html">concern</a> because it allows for optimal replication at 33 C, the temperature of a human nose in the winter, in contrast to E627, which is in the avian version of PB2 and allows for optimal replication at 41 C, the body temperature of birds. The PB2 in the swine is of avian origin, and A/Shanghi/71T/2009 is the first public sequence from the circulating sub-clade with E627K.

In human seasonal flu, activity peaks in the winter months and only minimal levels are detected in humans over the summer. However, the swine flu has <a rel="nofollow" href="http://www.recombinomics.com/News/06010901/H1N1_Swine_Summer.html">remained active</a> and almost all influenza A detected in the northern hemisphere at this time is swine flu.

The appearance of E627K raises concerns that the level of swine flu with E627K will markedly increase in colder months. In 1918, the flu in the spring was mild, but the fall version of the virus, which had E627K, was much more virulent and targeted young, previously healthy adults, as previously <a rel="nofollow" href="http://www.recombinomics.com/News/05080901/Swine_H1N1_Mexico_Fatalities.html">reported</a> for the outbreak in Mexico, and now being reported in United States and Canada, where levels are highest, as well as other countries worldwide.

Although the current case fatality rate is low, small changes like E627K could increase viral load, leading to high cytokine levels, which are associated with many of the deaths due to the current "milder" version of the swine H1N1. In contrast to the recent isolate from Brazil, A/Sao Paulo/1454/2009 which is identical to the HA consensus sequence, the A/Shanghai/71T/2009 has a unique change that is not found in closely related sequences.

This change is found in other H1N1 swine sequences (see list here) and the region surrounding E627K matches H3N2 seasonal flu in circulation in 1995. Moreover, the downstream region matches sequences found in human lethal infections in the H7N7 outbreak in the Netherlands in 2003, as well as the H5N1 outbreak in Hong Kong in 1997 (see matches here). However, in the above outbreaks transmission to humans was not efficient and the number of deaths was limited. The only reported death in the H7N7 outbreak was a veterinarian infected with nH7N7 containing E627K (and that case remains the only example of a human fatal bird flu infection not involving H5N1). The H5N1 sequence from Hong Kong was used to show the association of E627K with increased virulence in mice.

Thus, the acquisition of PB2 E627K in the swine H1N1 is readily explain by homologous recombination with locally related sequences containing E627K, which was a concern when the swine H1N1 began transmitting efficiently in humans . This sustained efficient transmission lead to a phase 6 designation for the 2009 pandemic and the acquisition of E627K creates concern that the virus will evolve into a more lethal agent that will be associated with an increased case fatality rate with previously healthy young adults, as was seen in the 1918 pandemic.


.

[The Mountains Voice]

Re: A/Shanghai/71T/2009 acquired E627K

Acquisition of E627K is a concern because it allows for optimal replication at 33 C, the temperature of a human nose in the winter, in contrast to E627, which is in the avian version of PB2 and allows for optimal replication at 41 C, the body temperature of birds.

Niman, Mama, GS and all the rest of you who understand the science behind all of this - THANK YOU for all of the clarifications and laymen speak. I have followed the "scientific level" discussions of this sort for years - and often my mind just goes poof! But it is very comforting to know that we have people such as yourselves that add legitimacy to the site, and help the rest of us begin to grasp all the complex science of things. It is so helpful to the rest of us to occassionally have these little "Easily Worded Summaries for the Ignorant Laymen" Thank You all.

[prepdeb]

Re: A/Shanghai/71T/2009 acquired E627K

Niman, Mama, GS and all the rest of you who understand the science behind all of this - THANK YOU for all of the clarifications and laymen speak. I have followed the "scientific level" discussions of this sort for years - and often my mind just goes poof! But it is very comforting to know that we have people such as yourselves that add legitimacy to the site, and help the rest of us begin to grasp all the complex science of things. It is so helpful to the rest of us to occassionally have these little "Easily Worded Summaries for the Ignorant Laymen" Thank You all.

Well stated Mountains Voice. I ditto that comment!

[gsgs]

Re: A/Shanghai/71T/2009 acquired E627K

all what the laymen need are expert probability estimates and
damage expectation values.
The discussion is being done to improve these estimates.

[gsgs]

Re: A/Shanghai/71T/2009 acquired E627K

they isolate these sequences, upload to genbank, but give no
comments on the mutation, not even location,age, travel history,
how they grew it etc.

do I see a new strategy of secrecy here ?

sequences are being uploaded, even all 8 segments from China,
but circumstances and details remain secret.

[Mamabird]

Re: A/Shanghai/71T/2009 acquired E627K

the fact that we have possible reassortment and E627K
in the same virus together with the other 4 mutations
close to 627 in PB2 lets me assume that it's somehow
a lab error.

A second A/Shanghai/71T sequence has been posted to GISAID, this time with c2 passage. Same result. Lab error beginning to seem less likely. Lets continue to keep a lookout for other isolates with this nasty change.

[HenryN]

Re: A/Shanghai/71T/2009 acquired E627K

all what the laymen need are expert probability estimates and
damage expectation values.
The discussion is being done to improve these estimates.

Speaking of probability estimates, do you still think that there is a 20% chance that the 2009 Pandemic isn't a pandemic?????