UK Genetic Evaluation thread

JJackson · Jan 10, 2011

Re: UK Genetic Evaluation thread

Mixin as I know you know - because we have discussed it before - the medium of passage is not neutral on the sample being passaged.

When a swab is taken it does not have enough virus in it to get a sequence from RT PCR so it is grown on (passaged) in a cell medium to grow more virus. If you grow virus in an egg medium each successive passage will tend to be better egg optimised. If you passage in MDCK (a mammalian medium) then the virus adapts to that medium and the resultant viral strain will not be quiet the same as either the original or that grown in egg. In both cases, if one were available, it would have been better to grow in a human culture medium to increase the amount of virus ready for RT PCR analysis as this would have been neutral (for a fully human adapted virus). There are various modified MDCK growth medium in the SIAT range which are genetically modified MDCK cells which attempt to reduce the MDCK skewing effect and are more neutral.

In this case all I can do is assume that Victoria-lineage is getting close to vaccine escape and that having been passaged through eggs is modified to the point where it becomes a sufficiently poor match from the test antisera - presumably California/7 [Edit: California/7 should read B/Brisbane/60/2008] (the vaccine strain) - to give a 'low reactor' status. Grown on in MDCK it is again modified but this time the result 'passes' the HI test. However in neither case can we say if the swab sample was a 'low reactor' that MDCK passage modified so it could pass the HI test or was it originally OK and the egg medium modified it to fail (although this is more likely). What I would say is it must be borderline, or near borderline, to begin with or the selective pressure caused by the growth medium would not have been enough to push into - or out of - the 'low reactor' zone.

This link is to the Sequences: The different methods of passage thread which you started and we both posted in a year ago as it may be helpful to others who are new to this area.

mixin · Jan 10, 2011

Re: UK Genetic Evaluation thread

We do have hundreds of examples where the method of passage produces different results with the same strain. Are the mutations always there and the method of passage just coaxes them out? I notice when they are testing for low reactivity, they most often use combinations of Siat and/or MDCK.

Just to note... the Victoria lineage that has the low reactors is influenza B.

JJackson · Jan 10, 2011

Re: UK Genetic Evaluation thread

mixin said:
Just to note... the Victoria lineage that has the low reactors is influenza B.

Thanks mixin - sorry all. I forgot what I was writing about

. Where I put California/7 in my last post it should have been B/Brisbane/60/2008-like virus which is the 2010/11 Northern Hemisphere Type B component of the Trivalent Vaccine.

mixin said:
We do have hundreds of examples where the method of passage produces different results with the same strain. Are the mutations always there and the method of passage just coaxes them out? I notice when they are testing for low reactivity, they most often use combinations of Siat and/or MDCK.

If the swab included a mix of strains then the best adapted to the growth medium will be selected for. If it is pure then as flu's very sloppy RNA copy mechanism produces variations the best adapted of these will come to the fore. I assume when they are concerned about the medium leading to 'low reactors' then they will be careful to select the medium which applies the least selection pressure on the virus - which is probably one of the SIATs but I do not know which is supposed to be the most like growing in you or I.

Steffi · Jan 10, 2011

Re: UK Genetic Evaluation thread

#38 & #40 Surely those firms know of bio-risk free growth factors (even e-coli free) like http://www.orfgenetics.com/ produces ? Top of their field, aren't they?

gsgs · Jan 11, 2011

Re: UK Genetic Evaluation thread

so our best candidates for high lethalitily in UK

are 1056,1171,1403 ?

mixin · Jan 11, 2011

Re: UK Genetic Evaluation thread

gsgs said:
so our best candidates for high lethalitily in UK

are 1056,1171,1403 ?

I'm not sure what determines the best candidates?

Here's what I found:

All 11 have T658A, G1171A, C1408T

8 have G340A
6 have G605C
6 have T1056C

JJackson · Jan 11, 2011

Re: UK Genetic Evaluation thread

Steffi said:
#38 & #40 Surely those firms know of bio-risk free growth factors (even e-coli free) like http://www.orfgenetics.com/ produces ? Top of their field, aren't they?

Steffi
Not quite sure what you are asking here. If it is about the growth medium I hope the following helps (if it is not please repost and I will try again).

All viruses are obligate parasites which means they can not grow on an agar plate with appropriate nutrients, like a bacteria, they can only reproduce by infecting a living cell and ‘reprogramming’ it to produce viral proteins and nucleotides. The tricky bit is to keep a cell line growing indefinitely, outside of the organism it came from, and keep it unchanged so any lab can buy some. Ordinary animal cell die fairly quickly once placed in a growth medium.
Commercially the vaccine virus is grown in eggs which stay alive long enough to produce a useable quantity of harvestable virus but as discussed the virus will adapt to its host and bird cells are not a perfect match to human cells. Dog cells are at least mammalian, and therefore better, but sadly do not lay eggs. Occasionally cancer cell lines develop which have the characteristic of dividing indefinitely and can be grown in a suitable growth medium (the medium is for the cell’s growth and the cell itself is the medium for the virus’ growth). MDCK (Madin-Darby Canine Kidney) came from a cocker spaniel in 1958 and has been growing in labs ever since. Baxters have patented a system for producing flu vaccine by cell culture using Vero cells, which came from an African green monkey (incidental the original source for Ebola), and there is a famous human cell line called HeLa after Henrietta Lacks who died in 1951 (the fame is mainly due to the Supreme Court ruling which set the precedent regarding who profits from such cell lines – hint: it wasn't Henrietta - follow the link for the Wikipedia article).

The obvious question, which I hope someone more knowledgeable than I can answer, is why are we using egg and MDCK for these test rather than HeLa (and there are others) which, being human, should be a more neutral growth medium I am sure there is a logical answer I just don’t know it.

NS1 · Jan 12, 2011

UK Severe Wave Demonstrates Diversity with Vaccine Escape Positional Changes

UK Severe Wave Demonstrates Diversity with Vaccine Escape Positional Changes

UK Severe Wave Demonstrates Diversity with Vaccine Escape Positional Changes
The UK Health Protection Agency released a group of 37 sequences at GISAID dated 2010-01-05 that appeared sometime after that date. Some of the sequences in this deposit also appear on the Figure 3 Phylogenetic Tree from the HPA Eurosurveilance paper requested to be cited as:

Ellis J, Galiano M, Pebody R, Lackenby A, Thompson C, Bermingham A, McLean E, Zhao H, Bolotin S, Dar O, Watson JM, Zambon M. Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010/11. Euro Surveill. 2011;16(1)

ii=19760. 
Available online:
<a href="http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19760" target="_blank">http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19760</a> 
Date of submission: 31 December 2010

Amino acid positions 158 and 159 have been tracked with changes associated with multiple "Low Reactor" specimens.

188T with 225G - UKEngland4880378_2010_12 [<a href="http://pf11.blogspot.com/2011/01/uk-severe-wave-sequences-show-no.html">Link</a>]
188T with 158E - UKEngland106_2010_11

Where is 188T with 158E and 225G similar to domained 156E, 188T and 225G on <a href="http://pf11.blogspot.com/2010/12/ha-225g-paired-with-188t-in-diverse.html" target="_blank">OzBrisbane209_51F_2010_08_09</a>?

<a href="http://genewurx.com/data/GeneWurx_UK_December_Emerging_Genetics_v4.xls" target="_blank">GeneWurx_UK_December_Emerging_Genetics_v4.xls</a>

. . . . UKEngland106_2010_11 (
. . . . . . . . 0A,
. . . . . . . . syn55L,
. . . . . . . . 158E mix wt,
. . . . . . . . 188T,
. . . . . . . . syn258F [RussiaPermCREI_ZTS_2009_11_30
. . . . . . . . . . . . . . . . . . with 0A, 377K],
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . 452I [H3N8 nucleotide donor],
. . . . . . . . . . . . [H11 nucleotide donor],
. . . . . . . . 454N,
. . . . . . . . syn529L)

. . . . UKEngland3380426_2010_08 (
. . . . . . . . syn44L,
. . . . . . . . syn106E,
. . . . . . . . 128D,
. . . . . . . . 159K [NY3230_2010_01_25
. . . . . . . . . . . . with 100N, syn177L, syn231N],
. . . . . . . . 377K)

gsgs · Jan 12, 2011

Re: UK Genetic Evaluation thread

they should give the vaccination status in the sample !

mixin · Jan 12, 2011

Re: UK Genetic Evaluation thread

June 24, 2010: The Wellcome Trust Influenza Research Team held a satellite workshop meeting at the Pacific Health Summit 2010 to review the team's activities and those of its partners in the context of the 2009 H1N1 pandemic and to discuss implementation of the recently posted World Health Organization Public Health Research Agenda for Influenza.

http://www.wellcome.ac.uk/About-us/...Influenza/UK-pandemic-H1N1-projects/index.htm

In the report on the Mosaic (Mechanisms of Severe Acute Influenza Consortium) project, Fred Hayden describes it as a multi-centre project designed to examine severe flu in hospitalized patients. It involves about 45 investigators in 8 major research centers in England and Scotland. It aims to obtain samples from 500 hospitalized patients to investigate virology, bacteriology, host genetics, cellular immunology and immune mediators.

Obtaining research & development approval for each hospital delayed the project...it took about 8 months to get R&D approval for one participating hospital. Despite the hurtles, they managed to recruit a small cohort from the second wave.

Over 2000 samples have been collected and stored (June 24, 2020).

Of the 85 patients enrolled, only around 30% were H1N1 positive, with 2 fatalities.

Investigators are currently analysing the initial samples before the next wave of subjects is anticipated to be recruited during the 2010-2011 flu season. (My comment: With the numbers of flu patients now, this should be easy to recruit the numbers they need)

Here's the clinical trial:
http://clinicaltrials.gov/show/NCT00965354

Primary Outcome Measures:
Detailed clinical phenotype. Clinicopathological correlation will then be sought between the clinical phenotype and pathological parameters measured as per work packages. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
Response to drug treatment and the effect of drug resistance if that emerges. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

A) Swabs and secretions from the nose and throat B) Blood C) Sputum D) Urine E) Stool

In addition, if the patients are having further respiratory sample collection as part of their routine care, for example tracheal aspirates, bronchial lavage and other samples then we would like to take an additional amount of these samples for our research.

Estimated Enrollment: 500
Study Start Date: December 2009
Estimated Study Completion Date: July 2012
Estimated Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)

:tiphat: to Wellcome Trust.

gsgs · Jan 12, 2011

Re: UK Genetic Evaluation thread

> Estimated Study Completion Date: July 2012

can we wait so long ?

we must decide now, whether to vaccinate the population
only a few weeks left for central Europe

mixin · Jan 12, 2011

Re: UK Genetic Evaluation thread

I spent some time converting the nucleotide changes to amino acids and then compared Eurosurveillance's lineages. If anyone sees an error, please feel free to point it out.

All UK 2010 viruses cluster in two main branches, characterised by either E374K with additional mutations in minor subclusters such as D97N, S185T, S451N and N125D, some of which have been recently described [10], or by A134T and S183P, with additional substitutions such as N441K, R509M and V527I.

Here's my conversion table showing all the letters and numbers associated. The first E374K is Euro's and we need to add 17 to it, the second number we often seen used (377) needs 14 added in order to get the actual position (391) in the sequence submission. I wish everyone would use the same numbering system when researching this flu.

G1171A is the nucleotide change and its codon is 1171, 1172 and 1173, which is gag (aag in its mutated form).

#1: E374K, with the other 4 listed below
E374K, 377, E391 = G1171A, (gag: 1171,72,73)
D97N, 100, D114 = G340A (gat: 340,41,42)
N125D, 128, N142 = A424G (aat: 424,25,26)
S185T, 188, S202 = G605A (agt: 604,05,06)
S451N, 454 S468 = G1403A (agc: 1402,03,04)

#2: A134T (G451A) and S183P (T598C) with the others listed below
A134T, 137, A151 = G451A (gca 451,52,53)
S183P, 186, S200 = T598C (tct: 598,99,600)
N441K, 444, N458 = T1374G (aat: 1372,73,74)
R509M, 512, R526 = G1577T (agg: 1576,77,78)
V527I, 530, V544 = G1630A (gta: 1630,31,32)

NS1 · Jan 12, 2011

Two Branching Polymorphisms Equates to a Minimum of 4 Branches

Two Branching Polymorphisms Equates to a Minimum of 4 Branches

mixin said:
I spent some time converting the nucleotide changes to amino acids and then compared Eurosurveillance's lineages. If anyone sees an error, please feel free to point it out.

Here's my conversion table showing all the letters and numbers associated. The first E374K is Euro's and we need to add 17 to it, the second number we often seen used (377) needs 14 added in order to get the actual position (391) in the sequence submission. I wish everyone would use the same numbering system when researching this flu.

G1171A is the nucleotide change and its codon is 1171, 1172 and 1173, which is gag (aag in its mutated form).

#1: E374K, with the other 4 listed below
E374K, 377, E391 = G1171A, (gag: 1171,72,73)
D97N, 100, D114 = G340A (gat: 340,41,42)
N125D, 128, N142 = A424G (aat: 424,25,26)
S185T, 188, S202 = G605A (agt: 604,05,06)
S451N, 454 S468 = G1403A (agc: 1402,03,04)

#2: A134T (G451A) and S183P (T598C) with the others listed below
A134T, 137, A151 = G451A (gca 451,52,53)
S183P, 186, S200 = T598C (tct: 598,99,600)
N441K, 444, N458 = T1374G (aat: 1372,73,74)
R509M, 512, R526 = G1577T (agg: 1576,77,78)
V527I, 530, V544 = G1630A (gta: 1630,31,32)

Phylogenetically, each branching polymorphism creates at least two branches . . . correct?

If the tree describes independent branching at 377 AND describes independent branching at 137, then the sequences show a minimum of four branches resulting from the two "OR" gates.

The actual tree and the detail of these sequences show highly divergent behaviour with many more branches than just these minimum of four that logic requires us to see. Does the logic gateway on a tree equate to a "This" OR "That" translation?

377K OR absence / other
137T OR absence / other

UK_2010_Phylo_ELLIS_Fig3new_4_GISAID_Notated_2011_01_08.jpg

For such a small group of geographically and temporally related sequences, only a low count of leaf clusters exists and even those are sparse in population. The sheer volume of novel and rare polymorphisms coupled with the homology to animal reservoirs establishes diversity.

Moreover, viral behaviour is based on the particular combination of changes. Each combination presents a potentially new clinical behaviour.

We cannot depend on a single nucleotide polymorphism to always confer the same outcome on different backgrounds. For example, a specimen elucidating changes at (A, B, C) may have a more profound clinical outcome than one showing changes at (A, B, C, D) . . . due to propensities that are not well characterised. The elasticity moves in the other direction as well. Many times, a greater number of seemingly minor or silent changes may have a profoundly stronger effect than a single synonymous change.

Ergo, we cannot count on an additive effect or subtractive effect based on deemed individual powers of individual polymorphisms.

Thank you for reorganising the data to reflect the amino acid level, mixin. Let's continue working on the interpretations based on the given data.

Gather & Solve.

NS1 · Jan 13, 2011

UK and Iran Transmit Hyper-Zoonotic Genetics in Late 2010

UK and Iran Transmit Hyper-Zoonotic Genetics in Late 2010

UK and Iran Transmit Hyper-Zoonotic Genetics in Late 2010

The Tehran University of Medical Sciences has made available 3 sets of sequences at GenBank recently that were sampled on 2010_10_02 with 2 additional divergent samples taken on 2010-12-06. These sequences directly parallel the developments from the UK Severe Wave and additionally feature hyper-zoonotic, sub-segment HA genetic acquisition.

Though considerable divergency is currently being demonstrated within the recent UK severe wave, two different sets of combinations have been coalescing throughout the world since late 2009 and have begun forming sub-clades in the past 4 months that are demonstrated well in these 3 Iranian sequences.

Do these Iranian sequences signal the type of zoonotic genetic behaviour that is driving some areas of the UK today to report an 800% rise in the number ill from Pandemic H1N1?

Though the origins of the primary branching polymorphisms begin much earlier, the later stages of transmission during late Summer and early Fall 2010 (Northern Hemisphere designations) more clearly distinguish the coalescence. Florida13 and Florida14 during August 2010 are recorded as having progenitor co-circulation of these two divergent sub-clades that transmitted and continued into the UK and Iran. Florida13_2010_08_02 has 4 of the same SNPs as IranBandarAbbas5096_2010_10_02. 100% of those matches [4 of 4 (137T, 186P, 377G, syn474C)] between Florida and Iran are also found in animal reservoirs.

Recall that small incursions of genetics from animal reservoirs are known to imbalance viral behaviour in the new human host. The HA 377G found on Florida13 and BandarAbbas5096 exists on the fatal UKEngland4500186_2010_11_f sequence and four other UK sequences from October and November of 2010, but was not notated on the HPA Ellis Figure3 1 phylogenetic tree.

<ul>
<li>UKEngland83_2010_10</li>
<li>UKEngland87_2010_10</li>
<li>UKEngland5500192_2010_10</li>
<li>UKEngland119_2010_11</li>
<li>UKEngland4500186_2010_11_f</li>
</ul>
GeneWurx has annotated the Ellis Figure3 1 phylogenetic tree with green boxes next to the four fatal GISAID 2010-12-20 deposited sequences and has proposed polymorphism notations including the zoonotic HA 377G on various unmarked branches in an attempt to provide clarity. <a href="http://genewurx.com/data/GeneWurx_UK_December_Emerging_Genetics_v5.xls" target="_blank">Version 5</a> of the Emerging Genetics spreadsheet is available with the Iranian sequences, the 4 representative UK 377G sequences (UKEngland5500192_2010_10 is identical to UKEngland87_2010_10) and the majority of the released UK fatalities.
<ul>
<li><a href="http://genewurx.com/data/UK_2010_Phylo_ELLIS_Fig3new_4_GISAID_Notated_2011_01_13.JPG" target="_blank">UK_2010_Phylo_ELLIS_Fig3new_4_GISAID_Notated_2011_01_13.JPG</a></li>
<li><a href="http://genewurx.com/data/GeneWurx_UK_December_Emerging_Genetics_v5.xls" target="_blank">GeneWurx_UK_December_Emerging_Genetics_v5.xls</a></li>
</ul>

The IranShahriar5336_2010_12_06 evaluation details a remarkable hyper-zoonosis. At least 78% of the polymorphisms (7 of 9) are clearly demonstrated as amino acid variation or single nucleotide polymorphisms in animal reservoirs, primarily H3N8, H5N1 and H7N7. Wisconsin08_2010_08_10 shares homology at 7 of the IranShahriar5336_2010_12_06 SNPs. 86% of those matches [6 of 7 (137T, 186P, syn297N, 388K, 444K, syn474C)] between Wisconsin and Iran are found in animals (5 in H3N8).

The homology between Iran and the UK is more striking than either of these vivid US examples and may be well visualised by scrolling through the GeneWurx <a href="http://genewurx.com/data/GeneWurx_UK_December_Emerging_Genetics_v5.xls" target="_blank">v5 spreadsheet</a> detailing these specific changes with combinational development over the course of this pandemic.

. . . . IranShahriar5336_2010_12_06 (
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . syn297N [H3N8 gadwallRussiaAltai1325_2007_09],
. . . . . . . . . . . . . . . [H5N1],
. . . . . . . . . . . . . . . [Wisconsin08_2010_08_10
. . . . . . . . . . . . . . . . . . . . . . with 39R, syn78S, 137T, 186P, syn297N,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn326S, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn413K, 444K, syn474C,
. . . . . . . . . . . . . . . CalifVRDL2_2010_01_11
. . . . . . . . . . . . . . . . . . . . . . with syn121P & 502K,
. . . . . . . . . . . . . . . YaroslavlIIV196_2009_12_04_f
. . . . . . . . . . . . . . . . . . . . . . with syn159N, 225G,
. . . . . . . . . . . . . . . WiscD0128_2009_11_15
. . . . . . . . . . . . . . . . . . . . . . with syn343G, 377G, 471H,
. . . . . . . . . . . . . . . Brussels243_2009_11_09
. . . . . . . . . . . . . . . . . . . . . . with syn44L, syn159N & syn323N,
. . . . . . . . . . . . . . . Australia6_2009_07_18
. . . . . . . . . . . . . . . . . . . . . . with syn159N, 233H]
. . . . . . . . syn326S [Wisconsin08_2010_08_10
. . . . . . . . . . . . . . . . . . . . . . with 39R, syn78S, 137T, 186P, syn297N,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn326S, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn413K, 444K, syn474C,
. . . . . . . . . . . . . . . Zhongyuan1643_2009_11_16
. . . . . . . . . . . . . . . . . . . . . . with 208G],
. . . . . . . . syn383N [H3N8],
. . . . . . . . syn388K [H3N8, H5N1, S7],
. . . . . . . . . . . . . . . [OzVictoria508_2010_07_24
. . . . . . . . . . . . . . . . . . . . . . . with 238D,
. . . . . . . . . . . . . . . swIowa44837_1_2009_11_08_xL
. . . . . . . . . . . . . . . . . . . . . . . with 188R, 225N & 230I,
. . . . . . . . . . . . . . . Utah20_C2_2_2009_07_25_VxX
. . . . . . . . . . . . . . . . . . . . . . . with 159D & 227G, et al],
. . . . . . . . syn411N (AAc) [H7N3 & H7N7 donor ATc],
. . . . . . . . 444K (AAg) [H3N8 gAg],
. . . . . . . . syn474C [H3N8, Avian H1N1 2010],
. . . . . . . . . . . . . . . [Michigan10_2009_06_03 with 137T, 225N, et al])

. . . . IranBandarAbbas5096_2010_10_02 (
. . . . . . . . 72P,
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . syn318A,
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . . . . . . [Florida13_2010_08_02
. . . . . . . . . . . . . . . . . . . with 137T, 186P, syn474C, 512M,
. . . . . . . . . . . . . . Iowa05_2010_05_04
. . . . . . . . . . . . . . . . . . . with 208K, syn516I,
. . . . . . . . . . . . . . swSouthDakota1_2010_04_27,
. . . . . . . . . . . . . . TexasAF2647_2010_04_11
. . . . . . . . . . . . . . . . . . . with 200S, syn214K, syn276H,
. . . . . . . . . . . . . . swIowa02999_2010_04_01,
. . . . . . . . . . . . . . UtahAF2653_2010_03_14
. . . . . . . . . . . . . . . . . . . with syn253V,
. . . . . . . . . . . . . . North Carolina05_2010_02_24
. . . . . . . . . . . . . . . . . . . with 259V,
. . . . . . . . . . . . . . Kentucky04_2010_02_22
. . . . . . . . . . . . . . . . . . . with syn488D,
. . . . . . . . . . . . . . Minnesota02_2010_02_17
. . . . . . . . . . . . . . . . . . . with 259V, 509D,
. . . . . . . . . . . . . . SouthCarolina01_2010_01_27
. . . . . . . . . . . . . . . . . . . with syn238E, syn488D,
. . . . . . . . . . . . . . AnasPlatBelgium04328_pcs17_2010_01_21
. . . . . . . . . . . . . . . . . . . with syn474C,
. . . . . . . . . . . . . . GermanyAF2208_2010_01_20
. . . . . . . . . . . . . . . . . . . with #1T, 225E,
. . . . . . . . . . . . . . NorthCarolina03_2010_01_20
. . . . . . . . . . . . . . . . . . . with 225G mix, 259V, syn275V,
. . . . . . . . . . . . . . NewMexico01_2010_01_05
. . . . . . . . . . . . . . . . . . . with 430I, syn445V, syn490P,
. . . . . . . . . . . . . . swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . with #1T, 0A, 189T, syn338G,
. . . . . . . . . . . . . . . . . . . . . . syn451K, syn474C, syn456L, syn529L,
. . . . . . . . . . . . . . Moldova5053_2009_12_11
. . . . . . . . . . . . . . . . . . with 173R, 176I, 225A, 225G mix wt, syn286K,
. . . . . . . . . . . . . . WiscD0128_2009_11_15
. . . . . . . . . . . . . . . . . . . with syn297N, syn343G, 471H,
. . . . . . . . . . . . . . KoreaAF2411_2009_11_11
. . . . . . . . . . . . . . . . . . . with 237I, syn286K,
. . . . . . . . . . . . . . England94840077_2009_11
. . . . . . . . . . . . . . . . . . . with 259T,
. . . . . . . . . . . . . . BahrainN11892_2009_10
. . . . . . . . . . . . . . . . . . . with 208K,
. . . . . . . . . . . . . . Nevada16_2009_10_02
. . . . . . . . . . . . . . . . . . . with 464R mix wt,
. . . . . . . . . . . . . . Tasmania2005_2009_07_03
. . . . . . . . . . . . . . . . . . . with 289M,
. . . . . . . . . . . . . . Texas42303371_2009
. . . . . . . . . . . . . . . . . . . with syn456L, syn507K],
. . . . . . . . syn449Y (TAc) [H3N8 Ttc],
. . . . . . . . syn474C [H3N8])

. . . . IranKaraj5327_2010_12_06 (
. . . . . . . . syn34N [JapanKanagawa74_2010_10_16, et al],
. . . . . . . . 146G [JapanKanagawa74_2010_10_16, et al],
. . . . . . . . 188T [H7N7],
. . . . . . . . 200T,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn465N [OzBrisbane209_51F_2010_08_09,
. . . . . . . . . . . . . . . . . . . . with 156E & 225G,
. . . . . . . . . . . . . . CalifVRDL131_2009_12_30, et al],
. . . . . . . . syn538F [Brunei218_2010 with 188T])

A significant correlation exists between syn474C and 137T. 26 of 42 sequences bearing syn474C also carry 137T.

Supporting Sequences

. . . . UKEngland4500186_2010_11_f (
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . 190Y [Avian H6N1],
. . . . . . . . . . [SwedenMalmoe1_2010_01_01_xL
. . . . . . . . . . . . with 377K, syn413K,
. . . . . . . . . . Brasil7450_2009_07_22
. . . . . . . . . . . . with 157E mix wt],
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . . . . . . [IranBandarAbbas5096_2010_10_02
. . . . . . . . . . . . . . . . . . . with 137T, 186P, syn474C,
. . . . . . . . . . . . . Florida13_2010_08_02
. . . . . . . . . . . . . . . . . . . with 137T, 186P, syn474C, 512M,
. . . . . . . . . . . . . . Iowa05_2010_05_04
. . . . . . . . . . . . . . . . . . . with 208K, syn516I,
. . . . . . . . . . . . . . swSouthDakota1_2010_04_27,
. . . . . . . . . . . . . . TexasAF2647_2010_04_11
. . . . . . . . . . . . . . . . . . . with 200S, syn214K, syn276H,
. . . . . . . . . . . . . . swIowa02999_2010_04_01,
. . . . . . . . . . . . . . UtahAF2653_2010_03_14
. . . . . . . . . . . . . . . . . . . with syn253V,
. . . . . . . . . . . . . . North Carolina05_2010_02_24
. . . . . . . . . . . . . . . . . . . with 259V,
. . . . . . . . . . . . . . Kentucky04_2010_02_22
. . . . . . . . . . . . . . . . . . . with syn488D,
. . . . . . . . . . . . . . Minnesota02_2010_02_17
. . . . . . . . . . . . . . . . . . . with 259V, 509D,
. . . . . . . . . . . . . . SouthCarolina01_2010_01_27
. . . . . . . . . . . . . . . . . . . with syn238E, syn488D,
. . . . . . . . . . . . . . AnasPlatBelgium04328_pcs17_2010_01_21
. . . . . . . . . . . . . . . . . . . with syn474C,
. . . . . . . . . . . . . . GermanyAF2208_2010_01_20
. . . . . . . . . . . . . . . . . . . with #1T, 225E,
. . . . . . . . . . . . . . NorthCarolina03_2010_01_20
. . . . . . . . . . . . . . . . . . . with 225G mix, 259V, syn275V,
. . . . . . . . . . . . . . NewMexico01_2010_01_05
. . . . . . . . . . . . . . . . . . . with 430I, syn445V, syn490P,
. . . . . . . . . . . . . . swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . with #1T, 0A, 189T, syn338G,
. . . . . . . . . . . . . . . . . . . . . . syn451K, syn474C, syn456L, syn529L,
. . . . . . . . . . . . . . Moldova5053_2009_12_11
. . . . . . . . . . . . . . . . . . with 173R, 176I, 225A, 225G mix wt, syn286K,
. . . . . . . . . . . . . . WiscD0128_2009_11_15
. . . . . . . . . . . . . . . . . . . with syn297N, syn343G, 471H,
. . . . . . . . . . . . . . KoreaAF2411_2009_11_11
. . . . . . . . . . . . . . . . . . . with 237I, syn286K,
. . . . . . . . . . . . . . England94840077_2009_11
. . . . . . . . . . . . . . . . . . . with 259T,
. . . . . . . . . . . . . . BahrainN11892_2009_10
. . . . . . . . . . . . . . . . . . . with 208K,
. . . . . . . . . . . . . . Nevada16_2009_10_02
. . . . . . . . . . . . . . . . . . . with 464R mix wt,
. . . . . . . . . . . . . . Tasmania2005_2009_07_03
. . . . . . . . . . . . . . . . . . . with 289M,
. . . . . . . . . . . . . . Texas42303371_2009
. . . . . . . . . . . . . . . . . . . with syn456L, syn507K],
. . . . . . . . syn408E,
. . . . . . . . syn474C,
. . . . . . . . 512M,
. . . . . . . . 530I)

. . . . UKEngland119_2010_11 (
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . 188N,
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . 391A,
. . . . . . . . syn408E,
. . . . . . . . syn474C,
. . . . . . . . 512M,
. . . . . . . . 530I)

. . . . UKEngland83_2010_10 (
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . syn272D,
. . . . . . . . syn279N,
. . . . . . . . syn352Y,
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . syn408E,
. . . . . . . . syn474C,
. . . . . . . . 509G,
. . . . . . . . 512M,
. . . . . . . . 530I)

. . . . UKEngland87_2010_10 (
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . syn279N,
. . . . . . . . syn352Y,
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . syn408E,
. . . . . . . . syn474C,
. . . . . . . . 509G,
. . . . . . . . 512M,
. . . . . . . . 530I)

. . . . UKEngland5500192_2010_10 (
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . syn279N,
. . . . . . . . syn352Y,
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . syn408E,
. . . . . . . . syn474C,
. . . . . . . . 509G,
. . . . . . . . 512M,
. . . . . . . . 530I)

. . . . Utah20_C2_2_2009_07_25_VxX (
. . . . . . . . #12E,
. . . . . . . . 0I [Latvia12_649_2009_12_09,
. . . . . . . . . NY7426_2009_12_08,
. . . . . . . . . Tambov_FOS_2009_12_01_xL,
. . . . . . . . . Slovenia5555_2009_12,
. . . . . . . . . Slovenia5559_2009_12,
. . . . . . . . . Ivanovo_RNA_2009_11_24_xL_f with 225G, 225N,
. . . . . . . . . Stockholm107_2009_11_24,
. . . . . . . . . GD_Yuncheng51_2009_11_19,
. . . . . . . . . Guangdong1271_2009_11_19,
. . . . . . . . . Austria528378_2009_11_19,
. . . . . . . . . Latvia11_1133_2009_11_16,
. . . . . . . . . Latvia11_1133M_2009_11_16,
. . . . . . . . . Latvia11_575_2009_11_11,
. . . . . . . . . England94600039_2009_10_27,
. . . . . . . . . SwedenUmea8_2009_10_07,
. . . . . . . . . Managua2323_02_2009_08_18,
. . . . . . . . . Texas42163291_2009_06_16,
. . . . . . . . . Marseille3416_2009],
. . . . . . . . 159D,
. . . . . . . . 206S,
. . . . . . . . 227G mix,
. . . . . . . . 296H,
. . . . . . . . syn388K [H5N1],
. . . . . . . . 470I)

. . . . Rome709_2009_07_14 (
. . . . . . . . 35I,
. . . . . . . . syn41N,
. . . . . . . . syn93C,
. . . . . . . . syn96G,
. . . . . . . . 206S,
. . . . . . . . 388M,
. . . . . . . . syn456L,
. . . . . . . . 516X (Ann),
. . . . . . . . 517X (nTG))

. . . . Aarhus241_2009_11_26_xL (
. . . . . . . . 176I, ** connecting Europe to North America xL **
. . . . . . . . syn177L,
. . . . . . . . 206T,
. . . . . . . . 324I,
. . . . . . . . syn383N [India PF11],
. . . . . . . . syn413K [H9N2])

. . . . IndiaPune21115_2009_12 (
. . . . . . . . syn147F [H3N8 Avian, H4, H5, H6, H11],
. . . . . . . . . . . . . . [Yaroslavl_KMP_2009_08_25,
. . . . . . . . . . . . . . IndiaJalna9436_2009_08_30 with 226R,
. . . . . . . . . . . . . . Texas44301765_2009_08_30,
. . . . . . . . . . . . . . CalifVRDL99_2009_11_05,
. . . . . . . . . . . . . . Athens943_2009_06_12],
. . . . . . . . syn163K,
. . . . . . . . 233H,
. . . . . . . . 271T,
. . . . . . . . 289V [Ukraine123_2010_02_14_xL with 230I,
. . . . . . . . . . . . .UK_Glascow_SC10_2009_06 with 225G, et al],
. . . . . . . . 377K [H9N2],
. . . . . . . . syn383N)

. . . . SwedenStockholm5_2010_08_27 (
. . . . . . . . 137T [41 sequences at GISAID],
. . . . . . . . syn163K,
. . . . . . . . 186P,
. . . . . . . . syn363G [21 sequences at GISAID],
. . . . . . . . syn474C,
. . . . . . . . 525G mix [Unique to GISAID; Unique to GenBank])

. . . . OzCanberra8_2010_08_15 (
. . . . . . . . 137T,
. . . . . . . . syn163K,
. . . . . . . . 186P,
. . . . . . . . syn363G,
. . . . . . . . syn397G,
. . . . . . . . syn474C)

. . . . Florida13_2010_08_02 (
. . . . . . . . 51T,
. . . . . . . . 137T,
. . . . . . . . 186P,
. . . . . . . . syn363G,
. . . . . . . . 377G,
. . . . . . . . syn474C,
. . . . . . . . 512M)

. . . . India007_2010_06_17 (
. . . . . . . . 137T,
. . . . . . . . syn163K,
. . . . . . . . 186P,
. . . . . . . . syn363G,
. . . . . . . . syn378I,
. . . . . . . . syn474C)

. . . . India3725_2010_04_03 (
. . . . . . . . 137T,
. . . . . . . . syn167S,
. . . . . . . . 186P,
. . . . . . . . syn474C,
. . . . . . . . syn526S [Malmoe2_2010_05_07 with 89G])

. . . . swItaly85437_2009_12_09 mix (
. . . . . . . . syn40H,
. . . . . . . . 225E,
. . . . . . . . 226R,
. . . . . . . . 300S,
. . . . . . . . syn434N,
. . . . . . . . syn474C,
. . . . . . . . 530I)

. . . . Salekhard01_2009_xL_f (
. . . . . . . . . . . 89N,
. . . . . . . . . . . 158E [H3N8, H5N1],
. . . . . . . . . . . 165N [H9N2],
. . . . . . . . . . . syn168Y [H9N2],
. . . . . . . . . . . 225G,
. . . . . . . . . . . syn413K [H9N2],
. . . . . . . . . . . 444D)

. . . . CubaHabana7374_2010_01 (
. . . . . . . . HA truncated before aa05,
. . . . . . . . 28P,
. . . . . . . . syn32S,
. . . . . . . . 33G,
. . . . . . . . 165N,
. . . . . . . . 232H,
. . . . . . . . 275I,
. . . . . . . . syn287G,
. . . . . . . . syn305K,
. . . . . . . . syn346G,
. . . . . . . . 421M,
. . . . . . . . 432W,
. . . . . . . . 444Y,
. . . . . . . . HA truncated after aa535)

. . . . OzVictoria508_2010_07_24 (
. . . . . . . . 35I [H5N1],
. . . . . . . . 88P [H2N3, H5N1, H11],
. . . . . . . . . . . [HunanHechengSWL1616_2009-11-23,
. . . . . . . . . . . KoreaAF2376_2009_10_27
. . . . . . . . . . . . . . . with 280A and 290K],
. . . . . . . . syn102E [SingON2407_2009_12_13,
. . . . . . . . . . . . . . . Singapore544_2009_12_10,
. . . . . . . . . . . . . . . Brussels243_2009_11_09
. . . . . . . . . . . . . . . . . . . . with syn44L and 89G],
. . . . . . . . syn152I [CalifVRDL115_2009_12_04,
. . . . . . . . . . . . . . . NY6939_2009_12_11,
. . . . . . . . . . . . . . . tkOntarioFAV117_1C_2009_12_07
. . . . . . . . . . . . . . . . . . . . with 35I, syn219I, syn276H, syn456L, 463V, 523A,
. . . . . . . . . . . . . . . England1050_2009_12,
. . . . . . . . . . . . . . . Scotland103_2009_12,
. . . . . . . . . . . . . . . England1051_2009_12,
. . . . . . . . . . . . . . . ItalyAncona451_2009_11_27_f,
. . . . . . . . . . . . . . . NY6607_2009_11_24,
. . . . . . . . . . . . . . . CalifVRDL107_2009_11_15,
. . . . . . . . . . . . . . . CalifVRDL101_2009_11_05,
. . . . . . . . . . . . . . . DC_114_2009_11_04,
. . . . . . . . . . . . . . . England94800096_2009_11,
. . . . . . . . . . . . . . . Calif_SD35_2009_10_26,
. . . . . . . . . . . . . . . NY5447_2009_10_23,
. . . . . . . . . . . . . . . CalifVRDL84_2009_10_09,
. . . . . . . . . . . . . . . CalifVRDL87_2009_10_09,
. . . . . . . . . . . . . . . IndiaPune6196_2009_08,
. . . . . . . . . . . . . . . IndiaDhule9433_2009_08,
. . . . . . . . . . . . . . . SantoDomingoWR1057N_2009_07_02,
. . . . . . . . . . . . . . . SantoDomingoWR1058N_2009_07_02,
. . . . . . . . . . . . . . . SantoDomingoWR1059N_2009_06_30],
. . . . . . . . 206S,
. . . . . . . . syn219I [CalifVRDL115_2009_12_04
. . . . . . . . . . . . . . . . . with 35I, syn152I, syn276H, syn456L, 463V, 523A,
. . . . . . . . . . . . . . FL_Pen213_2009_11_17
. . . . . . . . . . . . . . . . . . . . with 35I, syn152I, 273A, syn456L, 463V, 523A,
. . . . . . . . . . . . . . CalifVRDL107_2009_11_15
. . . . . . . . . . . . . . . . . . . . with 35I, syn152I, syn276H, syn456L, 463V, 523A,
. . . . . . . . 238D (GAc) [H2N3, H7N3, H7N7],
. . . . . . . . . . . . . . . . . . [Belgorod2_2010-03-15 (GAt),
. . . . . . . . . . . . . . . . . . Kaliningrad01_2009_11_02 (GAt)
. . . . . . . . . . . . . . . . . . . . . . . . with 225E and 226R,
. . . . . . . . . . . . . . . . . . AthensINS398_2010-01-24 GAt),
. . . . . . . . . . . . . . . . . . KaliningradCRIE_DA_2009-09-26 (GAt),
. . . . . . . . . . . . . . . . . . KaliningradCRIE_KG_2009-09-25 (GAt),
. . . . . . . . . . . . . . . . . . KaliningradCRIE_MA_2009-09-25 (GAt),
. . . . . . . . . . . . . . . . . . KaliningradCRIE_SHD_2009-09-25 (GAt),
. . . . . . . . . . . . . . . . . . KaliningradCRIE_ZD_2009-09-25 (GAt)],
. . . . . . . . syn247A [Belize8756_2009_10_08,
. . . . . . . . . . . . . . . Singapore93_2009_06_22]
. . . . . . . . syn254P,
. . . . . . . . 272G [Niigata19_2009_12_31,
. . . . . . . . . . . . GuangdongSWL36_2009_11_29],
. . . . . . . . syn276H,
. . . . . . . . syn388K [H5N1],
. . . . . . . . . . . . . . . [NagasakiHA_10_28_2010_03_23
. . . . . . . . . . . . . . . . . . . . . with 22I,
. . . . . . . . . . . . . . . NagasakiHA_10_26_2010_03_15
. . . . . . . . . . . . . . . . . . . . . with 22I, syn103E,
. . . . . . . . . . . . . . . NagasakiHA_10_24_2010_03_08
. . . . . . . . . . . . . . . . . . . . . with syn103E,
. . . . . . . . . . . . . . . GuangxiLonganSWL1990_2010_02_08
. . . . . . . . . . . . . . . . . . . . . with 453K, syn462E,
. . . . . . . . . . . . . . . JiangxiDonghuSWL15_2010_01_04
. . . . . . . . . . . . . . . . . . . . . with syn106E, 149R, syn456L (TTg),
. . . . . . . . . . . . . . . ViennaINS142_2009_11_26
. . . . . . . . . . . . . . . . . . . . . with syn97D, 99T,
. . . . . . . . . . . . . . . CzechUsti208_2009_11_25
. . . . . . . . . . . . . . . . . . . . . with 268T,
. . . . . . . . . . . . . . . GhanaFS_1921_2009_11_11,
. . . . . . . . . . . . . . . Alaska44_2009_11_17
. . . . . . . . . . . . . . . . . . . . . with syn275V, 276N,
. . . . . . . . . . . . . . . CalifVRDL76_2009_09_21
. . . . . . . . . . . . . . . . . . . . . with syn283Q,
. . . . . . . . . . . . . . . Taiwan206_2009_09_18,
. . . . . . . . . . . . . . . Taiwan177_2009_09_18,
. . . . . . . . . . . . . . . Taiwan167_2009_09_18,
. . . . . . . . . . . . . . . Taiwan156_2009_09_18,
. . . . . . . . . . . . . . . Taiwan143_2009_09_15
. . . . . . . . . . . . . . . . . . . . . with 205E mix,
. . . . . . . . . . . . . . . Utah20_C2_2_2009_07_25_VxX
. . . . . . . . . . . . . . . . . . . . . with 159D, 206S, 227G
. . . . . . . . . . . . . . . Slovenia2687_2009_07_01
. . . . . . . . . . . . . . . . . . . . . with 35I, 206S],
. . . . . . . . syn456L,
. . . . . . . . 463V,
. . . . . . . . 523A [Nebraska02_2010_03_11,
. . . . . . . . . . . . NagasakiHA1022_2010_03_01_syn413K,
. . . . . . . . . . . . DomRepublic3768_2009_12_15,
. . . . . . . . . . . . NY6939_2009_12_11,
. . . . . . . . . . . . CalifVRDL115_2009_12_04,
. . . . . . . . . . . . NY6607_2009_11_24,
. . . . . . . . . . . . RheinlandPfalz81_2009_11_23,
. . . . . . . . . . . . Berlin210_2009_11_16,
. . . . . . . . . . . . BadenWurttemberg511_2009_11_16,
. . . . . . . . . . . . CalifVRDL107_2009_11_15,
. . . . . . . . . . . . FL_Pensacola40_2009_11_09,
. . . . . . . . . . . . CalifVRDL101_2009_11_05,
. . . . . . . . . . . . DC114_2009_11_04,
. . . . . . . . . . . . Calif_SD35_2009_10_26,
. . . . . . . . . . . . NY5447_2009_10_23,
. . . . . . . . . . . . CalifVRDL84_2009_10_09,
. . . . . . . . . . . . CalifVRDL87_2009_10_09,
. . . . . . . . . . . . KuwaitN13013_2009_08_31_syn413K])

. . . . Zhongyuan1643_2009_11_16 (131P, 208G, syn326S)

. . . . YaroslavlIIV196_2009_12_04_f (
. . . . . . . . . . . syn7C,
. . . . . . . . . . . 89G [H7N7],
. . . . . . . . . . . syn159N [H3N8, H9N2],
. . . . . . . . . . . 225G,
. . . . . . . . . . . syn297N [H5N1],
. . . . . . . . . . . syn319T [H5N1],
. . . . . . . . . . . syn428L [H5N1])

. . . . Australia6_2009_07_18 (
. . . . . . . . 89G [H7N7],
. . . . . . . . syn159N [H3N8, H9N2],
. . . . . . . . 233H,
. . . . . . . . syn297N [H5N1],
. . . . . . . . syn406R [1918, WSN33, S9, S7, M7])

. . . . CalifVRDL2_2010_01_11 (
. . . . . . . . syn121P,
. . . . . . . . syn193S [H3N8, H6N1],
. . . . . . . . 206T,
. . . . . . . . syn297N,
. . . . . . . . 377K [H9N2],
. . . . . . . . 502K [UkrTernopilN10_2009_10_28_xL_f with 225G,
. . . . . . . . . . . Oz_Victoria800_2010_06_02,
. . . . . . . . . . . SingGP2362_2010_05_18,
. . . . . . . . . . . Scandinavia (7),
. . . . . . . . . . . California33_2009_08_06,
. . . . . . . . . . . Michigan21_2009_08_07,
. . . . . . . . . . . SouthCarolina36_2009_09_02,
. . . . . . . . . . . SouthCarolina38_2009_09_17,
. . . . . . . . . . . Haiti534_2009_10_19,
. . . . . . . . . . . AlgeriaG2902_2009_12_09 mix with 225E,
. . . . . . . . . . . Egypt114_2009_12_06 with 225E,
. . . . . . . . . . . JapanPR1070_2009_07_10,
. . . . . . . . . . . ThailandTHB0438_2009_07_28,
. . . . . . . . . . . Jiangyin34_2009_08_16,
. . . . . . . . . . . GuangxiLongan1870_2009_12_16])

. . . . Brussels243_2009_11_09 (
. . . . . . . . #10T [KyrgyzstanBishkekWR0881T_2009_12_02,
. . . . . . . . . . . . IndiaPune9355_2009_08 with 225G,
. . . . . . . . . . . . IndiaPune8489_2009_08 with 237I,
. . . . . . . . . . . . IndiaPune6447_2009_08],
. . . . . . . . syn44L,
. . . . . . . . 89G [H7N7],
. . . . . . . . syn102E,
. . . . . . . . syn159N [H3N8, H9N2],
. . . . . . . . 202A,
. . . . . . . . 252L,
. . . . . . . . syn297N [H5N1],
. . . . . . . . syn323N,
. . . . . . . . syn413K [H2, H5N1, H9N2],
. . . . . . . . syn490P (CCg))

. . . . Tunisia1064_2010_01_18 (
. . . . . . . . syn30T,
. . . . . . . . syn181G,
. . . . . . . . syn182I,
. . . . . . . . 208K,
. . . . . . . . 225G,
. . . . . . . . 318S)

. . . . swThaiCURA4_2009_11 (
. . . . . . . . 226R,
. . . . . . . . 263D,
. . . . . . . . syn317L,
. . . . . . . . 318T,
. . . . . . . . syn350G,
. . . . . . . . 392H,
. . . . . . . . 414I,
. . . . . . . . syn484N)

. . . . Kansas03_2009_04_24_GQ168644 (
. . . . . . . . #1T,
. . . . . . . . syn161Y [H3N8 2009, H6N1, H9N2],
. . . . . . . . 186P mix,
. . . . . . . . syn456L)

. . . . Egypt114_2009_12_06 (
. . . . . . . . #1T,
. . . . . . . . 225E,
. . . . . . . . 300S,
. . . . . . . . 502K
. . . . . . . . syn512R)

. . . . SingGP2362_2010_05_18 (
[HA match to Oz_Victoria800_2010_06_02]
. . . . . . . . syn44L,
. . . . . . . . syn106E,
. . . . . . . . 128D,
. . . . . . . . 377K,
. . . . . . . . 502K,
. . . . . . . . syn529L (CTa) [UKWhiteChapel4880374_2010_11_28]

Lab Notes

377G
Origination Eval
[H2N3],
[H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
[H6N1 2009],
[Avian H1N1, tn]
[UKLiverpool_1951],
[1918]

H2N3 Extensive incl
swMO4296424_2006
avian Alaska 2007
avian MN 2008

H5N1 wt GGA
CAAAAGGCAATAGATGgG
CAAAgGGCAATAGATGgG = 4526
Indonesia160H_2005_11_08
EgyptN04823_4M_2009_05_25, Sharqeya
EgyptN04526_4M_2009_05_18, Daqahleya.
dkEgypt0877NLQP_2008_04_15
140727_muscdkViet48_2007

H6N1 wt GGA
tkBelgium1865/2009
tkBelgium19842/2008
mallMaryland887_2002
mallOhio249/1998
mallALB730/1981
tealAustralia1/1979
dkPA486/1969

1. Ellis J, Galiano M, Pebody R, Lackenby A, Thompson C, Bermingham A, McLean E, Zhao H, Bolotin S, Dar O, Watson JM, Zambon M. Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010/11. Euro Surveill. 2011;16(1)

ii=19760. Available online: <a href="http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19760">http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19760</a>

docfuz · Jan 13, 2011

Re: Two Branching Polymorphisms Equates to a Minimum of 4 Branches

Re: Two Branching Polymorphisms Equates to a Minimum of 4 Branches

NS1 said:
We cannot depend on a single nucleotide polymorphism to always confer the same outcome on different backgrounds. For example, a specimen elucidating changes at (A, B, C) may have a more profound clinical outcome than one showing changes at (A, B, C, D) . . . due to propensities that are not well characterised. The elasticity moves in the other direction as well. Many times, a greater number of seemingly minor or silent changes may have a profoundly stronger effect than a single synonymous change.

Ergo, we cannot count on an additive effect or subtractive effect based on deemed individual powers of individual polymorphisms.

Moreover, I think we cannot explain without doubts clinical outcome since this may not be based only on direct effects mediated by viral genome and proteins. I mean, it's not only that (A,B,C) may produce different clinical presentation and outcome from (A,B,C,D,...); it could well be that (A,B,C).X may be different from (A,B,C).Y where X and Y represent two different patients biological environment (immune system, genetics, endocrine system, ...). So influenza virus pathogenesis may be a result of the interaction with and not only of action against the human body.

This is, at present, one of the biggest problem regarding flu in the medical community. In Italy we're now entering in a UK-like situation. As it happened in 2009, some clustering of interesting polymorphism is happening now in Puglia and Piemonte, but it doesn't translate in similar clinical outcomes, even with similar treatments and clinical pre-conditions.

Let's hope that all your great work on sequencing will be taken by clinical researchers, too. As you say, gather and solve.

doc

p.s. thank you all for all your efforts on sequencing.

NS1 · Jan 13, 2011

Immune Dysregulation - A Function of Viral Genetics and Host Specificity

Immune Dysregulation - A Function of Viral Genetics and Host Specificity

docfuz said:
Moreover, I think we cannot explain without doubts clinical outcome since this may not be based only on direct effects mediated by viral genome and proteins. I mean, it's not only that (A,B,C) may produce different clinical presentation and outcome from (A,B,C,D,...); it could well be that (A,B,C).X may be different from (A,B,C).Y where X and Y represent two different patients biological environment (immune system, genetics, endocrine system, ...). So influenza virus pathogenesis may be a result of the interaction with and not only of action against the human body.

This is, at present, one of the biggest problem regarding flu in the medical community. In Italy we're now entering in a UK-like situation. As it happened in 2009, some clustering of interesting polymorphism is happening now in Puglia and Piemonte, but it doesn't translate in similar clinical outcomes, even with similar treatments and clinical pre-conditions.

Let's hope that all your great work on sequencing will be taken by clinical researchers, too. As you say, gather and solve.

doc

p.s. thank you all for all your efforts on sequencing.

Welcome DocFuz.

We wholeheartedly agree that any effort attempting to pin a specific population outcome to a specific SNP is highly improbable. You may have noticed our signature line:

Independent Primary Research on Viral Genetics and the
Host-Pathogen Immune Dynamics of Zoonotic Influenza Reservoirs

The Host-Pathogen Dynamic is the puzzle to solve. GeneWurx only evaluates these sequences with such verve so that we can establish what is known, what can be known, about the one side of the equation that is available (sometimes available, I should say). By constantly refining the ore and removing dross and slag, we work to purify thinking around the evidence, the observable facts.

Those who subscribe to the idea that the end-game is the viral genetics are misled and misleading.

Human life is the goal. Human life is managed at the host-pathogen interaction via immune function running under and within a system of programs (feedback loops, genetic, digestive, endocrine, neurological, vascular, et al) that is somewhat unique to each host. Add the complexity of the viral reservoir and the potential in situ adaptation / genetic variance that may occur in a particular host and the equational complexity begins to be understood.

When so little data may be elucited about particular cases, one may only take what is available (as basic research) in an attempt to increase the knowledge base beyond the current purely applied research that employs outmoded techniques and relies on the continuity of outdated mediation measures.

What is known?

Immune dysregulation via cytokinic dysregulation is a very certain outcome of emerging influenza genetics. Up and down regulation of various components of the human immune system are modulated at various timings using various methods trimmed by the viral genetics. Host specificity does come into play, but general precepts have been observed and documented.

This research is planned to establish touchpoints on an ongoing battlefield for clinicians, researchers and parents against a brilliant and constantly changing enemy. Those factual touchpoints we produce and the interpretations we postulate, devoid of political manuvering, may at some future event yield answers that have not been yet hypothesised or pursued under the current system of thinking and disease management.

Collaboration sometimes does produce novel thought and novel actions, a sorely missing requirement against an ever novel opponent, Pandemic Influenza.

What exactly are you seeing in your area, DocFuz?

mixin · Jan 13, 2011

Re: UK Genetic Evaluation thread

I re-grouped the branch, made up of A134T and S183P with N441K, R509M and V527I. Although it looks to me like it the main branch should include N441K with the smaller branch having R509M and V527I.

Regarding my codes: the first three letter/number combos are the three different numbering systems for the amino acids, the next is the nucleotide change, then the codon and the 3 positions that make it up and finally the changed position.

A134T, 137, A151 = G451A (gca 451,52,53 aca) and
S183P, 186, S200 = T598C (tct: 598,99,600 cct) with
N441K, 444, N458 = T1374G (aat: 1372,73,74 aag)
R509M, 512, R526 = G1577T (agg: 1576,77,78 atg)
V527I, 530, V544 = G1630A (gta: 1630,31,32 ata)

Clade B: A134T=(451), S183P=(598) PLUS N441K=(T1374G), R509M=(1577), V527I=(G1630A)

G451A,T598C,T658A,T933C,T1020C,T1191C,G1206A,C1245T,T1374G,C1408T,C1464T(4)
G451A,T598C,T658A,T933C,T1020C,T1191C,G1206A,C1245T,T1374G,C1408T,C1464T(4)
G451A,T598C,T658A,T933C,T1020C,T1191C,G1206A,C1245T,T1374G,C1408T,C1464T(4)
G451A,T598C,T658A,T933C,T1020C,T1191C,G1206A,C1245T,T1374G,C1408T,C1464T(4)
G451A,T598C,T658A,T933C,T1020C,T1191C,G1206A,C1245T,T1374G,G1403A,C1408T,C1464T(4)
G451A,T598C,T658A,T933C,T1020C,T1191C,G1206A,C1245T,T1374G,G1403A,C1408T,C1464T(4)
G451A,T598C,T658A,T933C,T1020C,T1191C,G1206A,C1245T,T1374G,C1408T,C1464T(4)
G451A,G531A,T598C,T658A,C921T,A1131G,C1408T,C1464T(4)
G396A,G451A,G531A,T598C,T658A,A795G,C921T,A1131G,G1407A,C1408T,C1464T,A1553G,A1579G(4)

G451A,T598C,T658A,T879C,C1098T,A1172G,G1266A,C1408T,C1464T,A1568G,G1577T,G1630A(4)
G451A,T598C,T658A,T879C,C1098T,A1172G,G1266A,C1408T,C1464T,A1568G,G1577T,G1630A(4)
G451A,T598C,T658A,T858C,T879C,C1098T,A1172G,G1266A,C1408T,C1464T,A1568G,G1577T,G1630A
G451A,T598C,G605A,T658A,A1172G,A1213G,G1266A,C1408T,C1464T,G1577T,G1630A(4)
G451A,T598C,G610T,T658A,A1172G,G1266A,C1408T,C1464T,G1577T,G1630A(4)F

NS1 · Jan 14, 2011

UK Fatality Sequences Relate to US and Iran

UK Fatality Sequences Relate to US and Iran

UK Fatality Sequences Relate to US and Iran

The US CDC today released a small set of sequences at GISAID spanning June to November 2010. As the UK Severe Wave is the current topic of interest, we have profiled 6 of these sequences from today against the UK Fatality Sequences that have been published. Five of the sequences are from the United States and one is from Bangladesh.

Previously, the UK HPA released a small group of sequences in two deposits at GISAID related to the present severe wave filling the ICU wards in the UK. A concurrent paper 1 was published in early January with a phylogenetic tree. Several of the fatalities noted on the HPA Ellis Figure3 1 phylogenetic tree have been included in the two sequence deposits.

So that focus may occur at the clinical outcomes of highest priority, GeneWurx has prepared a fresh <a href="http://genewurx.com/data/GeneWurx_Global_Spread_of_Divergence_UK_US_Iran_v0.JPG" target="_blank">phylogenetic tree</a> with annotation in progress that may prove useful to those investigating the ongoing divergency within this zoonoticly active pH1N1 <a href="http://pf11.blogspot.com/2011/01/uk-and-iran-transmit-hyper-zoonotic.html" target="_blank">viral reservoir</a>. UK Fatalities, UK Severe cases (225G), UK potential Vaccine Escape cases (158E, 159K) and cases from the US, Australia, Iran and Bangladesh are profiled.

<a href="http://genewurx.com/data/GeneWurx_Global_Spread_of_Divergence_UK_US_Iran_v0.JPG" target="_blank">GeneWurx_Global_Spread_of_Divergence_UK_US_Iran_v0.jpg</a>

The GeneWurx annotation for the full HPA Ellis Figure3 1 has been recently revised and <a href="http://genewurx.com/data/GeneWurx_UK_December_Emerging_Genetics_v5.xls" target="_blank">Version 5</a> of the Emerging Genetics spreadsheet is available with several additions including two of the recent US sequences of interest and the Bangladeshi sequence.
<ul>
<li><a href="http://genewurx.com/data/UK_2010_Phylo_ELLIS_Fig3new_4_GISAID_Notated_2011_01_13.JPG" target="_blank">UK_2010_Phylo_ELLIS_Fig3new_4_GISAID_Notated_2011_01_13.JPG</a></li>
<li><a href="http://genewurx.com/data/GeneWurx_UK_December_Emerging_Genetics_v5.xls" target="_blank">GeneWurx_UK_December_Emerging_Genetics_v5.xls</a></li>
</ul>
A pattern that has been expected is demonstrated in Kentucky09_40F_2010_11_01 with 158E, 188T and 225G on a similar background as the OzBrisbane209_51F_2010_08_09 <a href="http://pf11.blogspot.com/2010/12/ha-225g-paired-with-188t-in-diverse.html">sequence</a> carrying 156E, 188T and 225G. Though these two sequences share extensive homology, the tree and polymorphism details will show that overall the reservoir is diversifying and creating branches with minimal leaf count by acquiring and recombining rare and novel polymorphisms also found in animal reservoirs.

US Sequences

. . . . Indiana05_78F_2010_06_11 (
. . . . . . . . 100N,
. . . . . . . . 115K,
. . . . . . . . syn270I,
. . . . . . . . 377K)

. . . . Indiana06_9M_2010_07_29 (
. . . . . . . . #11V,
. . . . . . . . #8A,
. . . . . . . . syn36L,
. . . . . . . . syn99I,
. . . . . . . . 233H,
. . . . . . . . syn256Y,
. . . . . . . . syn282C,
. . . . . . . . syn283Q,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn428L,
. . . . . . . . 522A)

. . . . Kentucky08_xF_2010_10_11 (
. . . . . . . . 100N,
. . . . . . . . syn179L,
. . . . . . . . 188T,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L,
. . . . . . . . 454N)

. . . . Utah05_29F_2010_10_12 (
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . 289M,
. . . . . . . . syn297N,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . 396I,
. . . . . . . . 454N,
. . . . . . . . syn478C)

. . . . Kentucky09_40F_2010_11_01 (
. . . . . . . . 17G,
. . . . . . . . 100N,
. . . . . . . . 158E,
. . . . . . . . syn179L,
. . . . . . . . 188T,
. . . . . . . . 225G,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L,
. . . . . . . . syn452V,
. . . . . . . . 454N,
. . . . . . . . syn467C)

Bangladesh Sequence

. . . . Bangladesh8003_27M_2010_09_16 (
. . . . . . . . syn12A,
. . . . . . . . 137T,
. . . . . . . . 186P,
. . . . . . . . 225N mix wt,
. . . . . . . . syn297N,
. . . . . . . . syn326S,
. . . . . . . . syn383N,
. . . . . . . . syn388K,
. . . . . . . . 444K,
. . . . . . . . 447S,
. . . . . . . . syn474C)

UK Fatality Sequences

. . . . UKEngland5040499_2010_12_f (
[match GhanaFS10_4259_2010_08_27 less 213S]
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . 213S,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S)

. . . . UKWhiteChapel4880374_2M_2010_11_28_f (
. . . . . . . . 0A [Arizona05_2010_05_01
. . . . . . . . . . . . . . . with syn338G & 377K,
. . . . . . . . . . Alabama08_2009_12_04
. . . . . . . . . . . . . . . with syn226Q, 310A mix & 506V,
. . . . . . . . . . RussiaPerm_ZTS_2009_11_30
. . . . . . . . . . . . . . . with 377K & syn475D,
. . . . . . . . . . RussiaBelgorod01_2009_11_30,
. . . . . . . . . . RussiaBelgorod05_2009_11_30,
. . . . . . . . . . Boston634_2009_11_09
. . . . . . . . . . . . . . . with 100N & syn270I],
. . . . . . . . syn55L [S9, H5N1],
. . . . . . . . . . . . . . [Iran16273_2009_11_22 with 226R
. . . . . . . . . . . . . . NZ_Waikato2_2010_01_04 with 233H,
. . . . . . . . . . . . . . tkOntarioFAV117_1C_2009_12_07, et al],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . . . . . . . . [OzBrisbane209_51F_2010_08_09
. . . . . . . . . . . . . . . . . . . . with 156E & 225G,
. . . . . . . . . . . . . . . Arizona05_2010_05_11 with 0A,
. . . . . . . . . . . . . . . Swine Asia 2005 with 0A, et al]
. . . . . . . . 377K,
. . . . . . . . 454N [H7N3, H7N7, H9N2]
. . . . . . . . . . [Florida14_24M_2010_08_05
. . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . FL_Pen210_2009_11_10
. . . . . . . . . . . . . . . . . . with 225E,
. . . . . . . . . . SouthCarolina18_2009_09_16_VxX
. . . . . . . . . . . . . . . . . . with 159D, 224K, et al],
. . . . . . . . syn529L)

. . . . UKCambridge118_4F_2010_11_19_f (
. . . . . . . . syn118E,
. . . . . . . . 137T [41 sequences at GISAID],
. . . . . . . . syn163K,
. . . . . . . . 186P,
. . . . . . . . syn251L,
. . . . . . . . syn293L,
. . . . . . . . syn363G [21 sequences at GISAID],
. . . . . . . . syn455Q,
. . . . . . . . syn474C,
. . . . . . . . 504G,
. . . . . . . . 513V)

. . . . UKEngland4500186_2010_11_f (
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . 190Y [Avian H6N1],
. . . . . . . . . . [SwedenMalmoe1_2010_01_01_xL
. . . . . . . . . . . . with 377K, syn413K,
. . . . . . . . . . Brasil7450_2009_07_22
. . . . . . . . . . . . with 157E mix wt],
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . . . . . . [IranBandarAbbas5096_2010_10_02
. . . . . . . . . . . . . . . . . . . with 137T, 186P, syn474C,
. . . . . . . . . . . . . Florida13_2010_08_02
. . . . . . . . . . . . . . . . . . . with 137T, 186P, syn474C, 512M,
. . . . . . . . . . . . . . Iowa05_2010_05_04
. . . . . . . . . . . . . . . . . . . with 208K, syn516I,
. . . . . . . . . . . . . . swSouthDakota1_2010_04_27,
. . . . . . . . . . . . . . TexasAF2647_2010_04_11
. . . . . . . . . . . . . . . . . . . with 200S, syn214K, syn276H,
. . . . . . . . . . . . . . swIowa02999_2010_04_01,
. . . . . . . . . . . . . . UtahAF2653_2010_03_14
. . . . . . . . . . . . . . . . . . . with syn253V,
. . . . . . . . . . . . . . North Carolina05_2010_02_24
. . . . . . . . . . . . . . . . . . . with 259V,
. . . . . . . . . . . . . . Kentucky04_2010_02_22
. . . . . . . . . . . . . . . . . . . with syn488D,
. . . . . . . . . . . . . . Minnesota02_2010_02_17
. . . . . . . . . . . . . . . . . . . with 259V, 509D,
. . . . . . . . . . . . . . SouthCarolina01_2010_01_27
. . . . . . . . . . . . . . . . . . . with syn238E, syn488D,
. . . . . . . . . . . . . . AnasPlatBelgium04328_pcs17_2010_01_21
. . . . . . . . . . . . . . . . . . . with syn474C,
. . . . . . . . . . . . . . GermanyAF2208_2010_01_20
. . . . . . . . . . . . . . . . . . . with #1T, 225E,
. . . . . . . . . . . . . . NorthCarolina03_2010_01_20
. . . . . . . . . . . . . . . . . . . with 225G mix, 259V, syn275V,
. . . . . . . . . . . . . . NewMexico01_2010_01_05
. . . . . . . . . . . . . . . . . . . with 430I, syn445V, syn490P,
. . . . . . . . . . . . . . swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . with #1T, 0A, 189T, syn338G,
. . . . . . . . . . . . . . . . . . . . . . syn451K, syn474C, syn456L, syn529L,
. . . . . . . . . . . . . . Moldova5053_2009_12_11
. . . . . . . . . . . . . . . . . . with 173R, 176I, 225A, 225G mix wt, syn286K,
. . . . . . . . . . . . . . WiscD0128_2009_11_15
. . . . . . . . . . . . . . . . . . . with syn297N, syn343G, 471H,
. . . . . . . . . . . . . . KoreaAF2411_2009_11_11
. . . . . . . . . . . . . . . . . . . with 237I, syn286K,
. . . . . . . . . . . . . . England94840077_2009_11
. . . . . . . . . . . . . . . . . . . with 259T,
. . . . . . . . . . . . . . BahrainN11892_2009_10
. . . . . . . . . . . . . . . . . . . with 208K,
. . . . . . . . . . . . . . Nevada16_2009_10_02
. . . . . . . . . . . . . . . . . . . with 464R mix wt,
. . . . . . . . . . . . . . Tasmania2005_2009_07_03
. . . . . . . . . . . . . . . . . . . with 289M,
. . . . . . . . . . . . . . Texas42303371_2009
. . . . . . . . . . . . . . . . . . . with syn456L, syn507K],
. . . . . . . . syn408E,
. . . . . . . . syn474C,
. . . . . . . . 512M,
. . . . . . . . 530I)

. . . . UKEngland4640543_2010_11_f (
[match to UKEngland4940476_2010_12 less 225G plus 190G]
. . . . . . . . 100N,
. . . . . . . . syn179L,
. . . . . . . . 188T,
. . . . . . . . 190G,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L,
. . . . . . . . 454N)

. . . . UKWhiteChapel4780352_5M_2010_10_26_f (
. . . . . . . . syn58C,
. . . . . . . . 100N,
. . . . . . . . 128D,
. . . . . . . . syn131S,
. . . . . . . . syn210S,
. . . . . . . . 377K)

. . . . UKEngland4380108_2010_10_f (
. . . . . . . . syn67N,
. . . . . . . . 100N,
. . . . . . . . 128D,
. . . . . . . . 144V [Boston703 and Ireland],
. . . . . . . . 224K,
. . . . . . . . syn235T,
. . . . . . . . 377K,
. . . . . . . . 529M)

. . . . UKBirmingham3220137_44F_2010_08_07_f (
. . . . . . . . #8A,
. . . . . . . . 175K,
. . . . . . . . 311E,
. . . . . . . . 377K,
. . . . . . . . syn385V,
. . . . . . . . syn451K,
. . . . . . . . syn454S,
. . . . . . . . syn494E,
. . . . . . . . 537G)

Severe Sequences

. . . . UKEngland4940476_2010_12 (
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg) [Regional Marker 2009 (tTA)]
. . . . . . . . . . . . . . . . . . . . [TexasAF2588_2009_10_04,
. . . . . . . . . . . . . . . . . . . . TexasJMS404_2010_01_08],
. . . . . . . . 188T,
. . . . . . . . 225G,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L [H6N1]
. . . . . . . . . . . . . . . [Regional Marker UK 2009]
. . . . . . . . . . . . . . . [UKEngland4880378_2010_12 with syn179L, 188T,
. . . . . . . . . . . . . . . UKEngland4640543_2010_11_f with syn179L, 188T, 190G
. . . . . . . . . . . . . . . UKEngland4920303_2010_11 with syn179L, 188T,
. . . . . . . . . . . . . . . UKEngland142_2010_11 with syn179L, 188T,
. . . . . . . . . . . . . . . UKEngland4860049_2010_11 with syn179L, 188T,
. . . . . . . . . . . . . . . UKEngland126_2010_11 with syn179L, 188T,
. . . . . . . . . . . . . . . NZChristchurch8_2010_07_08
. . . . . . . . . . . . . . . . . . . with syn44L, 97N, syn99I, syn106E, 128D,
. . . . . . . . . . . . . . . . . . . . . . . syn214K, 253A, syn362S, 377K,
. . . . . . . . . . . . . . . Calif06_2010_04_05 with 269V
. . . . . . . . . . . . . . . Hawaii08_2010_04_12
. . . . . . . . . . . . . . . . . . . with 159D, 269V, 312R, 313K,
. . . . . . . . . . . . . . . Ethiopia13_2010_02_10
. . . . . . . . . . . . . . . . . . . with 100N, syn163K, 269V, 324I, syn360Q, syn455Q,
. . . . . . . . . . . . . . . Philippines824_2010_02_17 with 165N,
. . . . . . . . . . . . . . . Kosova876_2009_12_22,
. . . . . . . . . . . . . . . RussiaYakutsk_EAV_2009_11_18,
. . . . . . . . . . . . . . . Netherlands2143_2009_11_16 with syn179L (tTA),
. . . . . . . . . . . . . . . RussiaYaroslavl_CHMV_2009_11_10_f with 224K & 225G mix
. . . . . . . . . . . . . . . AntwerpINS221_2009_10_28 with syn179L (tTA)],
. . . . . . . . 454N)

. . . . UKEngland4880378_2010_12 (
. . . . . . . . 100N,
. . . . . . . . syn179L,
. . . . . . . . 188T,
. . . . . . . . 225G,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L,
. . . . . . . . 454N)

Potential Vaccine Escape Sequences

[<a href="http://pf11.blogspot.com/2011/01/uk-severe-wave-demonstrates-diversity.html" target="_blank">Diversity with Vaccine Escape Potential</a>]

. . . . UKEngland106_2010_11 (
. . . . . . . . 0A,
. . . . . . . . syn55L,
. . . . . . . . 158E mix wt,
. . . . . . . . 188T,
. . . . . . . . syn258F,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . 452I [],
. . . . . . . . 454N,
. . . . . . . . syn529L)

. . . . UKEngland3380426_2010_08 (
. . . . . . . . syn44L,
. . . . . . . . syn106E,
. . . . . . . . 128D,
. . . . . . . . 159K [NY3230_2010_01_25 with 100N, syn177L, syn231N],
. . . . . . . . 377K)

Iran Sequences

. . . . IranShahriar5336_2010_12_06 (
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . syn297N [H3N8 gadwallRussiaAltai1325_2007_09],
. . . . . . . . . . . . . . . [H5N1],
. . . . . . . . . . . . . . . [Wisconsin08_2010_08_10
. . . . . . . . . . . . . . . . . . . . . . with 39R, syn78S, 137T, 186P, syn297N,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn326S, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn413K, 444K, syn474C,
. . . . . . . . . . . . . . . CalifVRDL2_2010_01_11
. . . . . . . . . . . . . . . . . . . . . . with syn121P & 502K,
. . . . . . . . . . . . . . . YaroslavlIIV196_2009_12_04_f
. . . . . . . . . . . . . . . . . . . . . . with syn159N, 225G,
. . . . . . . . . . . . . . . WiscD0128_2009_11_15
. . . . . . . . . . . . . . . . . . . . . . with syn343G, 377G, 471H,
. . . . . . . . . . . . . . . Brussels243_2009_11_09
. . . . . . . . . . . . . . . . . . . . . . with syn44L, syn159N & syn323N,
. . . . . . . . . . . . . . . Australia6_2009_07_18
. . . . . . . . . . . . . . . . . . . . . . with syn159N, 233H]
. . . . . . . . syn326S [Wisconsin08_2010_08_10
. . . . . . . . . . . . . . . . . . . . . . with 39R, syn78S, 137T, 186P, syn297N,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn326S, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn413K, 444K, syn474C,
. . . . . . . . . . . . . . . Zhongyuan1643_2009_11_16
. . . . . . . . . . . . . . . . . . . . . . with 208G],
. . . . . . . . syn383N [H3N8],
. . . . . . . . syn388K [H3N8, H5N1, S7],
. . . . . . . . . . . . . . . [OzVictoria508_2010_07_24
. . . . . . . . . . . . . . . . . . . . . . . with 238D,
. . . . . . . . . . . . . . . swIowa44837_1_2009_11_08_xL
. . . . . . . . . . . . . . . . . . . . . . . with 188R, 225N & 230I,
. . . . . . . . . . . . . . . Utah20_C2_2_2009_07_25_VxX
. . . . . . . . . . . . . . . . . . . . . . . with 159D & 227G, et al],
. . . . . . . . syn411N (AAc) [H7N3 & H7N7 donor ATc],
. . . . . . . . 444K (AAg) [H3N8 gAg],
. . . . . . . . syn474C [H3N8, Avian H1N1 2010],
. . . . . . . . . . . . . . . [Michigan10_2009_06_03 with 137T, 225N, et al])

. . . . IranBandarAbbas5096_2010_10_02 (
. . . . . . . . 72P,
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . syn318A,
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . . . . . . [Florida13_2010_08_02
. . . . . . . . . . . . . . . . . . . with 137T, 186P, syn474C, 512M,
. . . . . . . . . . . . . . Iowa05_2010_05_04
. . . . . . . . . . . . . . . . . . . with 208K, syn516I,
. . . . . . . . . . . . . . swSouthDakota1_2010_04_27,
. . . . . . . . . . . . . . TexasAF2647_2010_04_11
. . . . . . . . . . . . . . . . . . . with 200S, syn214K, syn276H,
. . . . . . . . . . . . . . swIowa02999_2010_04_01,
. . . . . . . . . . . . . . UtahAF2653_2010_03_14
. . . . . . . . . . . . . . . . . . . with syn253V,
. . . . . . . . . . . . . . North Carolina05_2010_02_24
. . . . . . . . . . . . . . . . . . . with 259V,
. . . . . . . . . . . . . . Kentucky04_2010_02_22
. . . . . . . . . . . . . . . . . . . with syn488D,
. . . . . . . . . . . . . . Minnesota02_2010_02_17
. . . . . . . . . . . . . . . . . . . with 259V, 509D,
. . . . . . . . . . . . . . SouthCarolina01_2010_01_27
. . . . . . . . . . . . . . . . . . . with syn238E, syn488D,
. . . . . . . . . . . . . . AnasPlatBelgium04328_pcs17_2010_01_21
. . . . . . . . . . . . . . . . . . . with syn474C,
. . . . . . . . . . . . . . GermanyAF2208_2010_01_20
. . . . . . . . . . . . . . . . . . . with #1T, 225E,
. . . . . . . . . . . . . . NorthCarolina03_2010_01_20
. . . . . . . . . . . . . . . . . . . with 225G mix, 259V, syn275V,
. . . . . . . . . . . . . . NewMexico01_2010_01_05
. . . . . . . . . . . . . . . . . . . with 430I, syn445V, syn490P,
. . . . . . . . . . . . . . swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . with #1T, 0A, 189T, syn338G,
. . . . . . . . . . . . . . . . . . . . . . syn451K, syn474C, syn456L, syn529L,
. . . . . . . . . . . . . . Moldova5053_2009_12_11
. . . . . . . . . . . . . . . . . . with 173R, 176I, 225A, 225G mix wt, syn286K,
. . . . . . . . . . . . . . WiscD0128_2009_11_15
. . . . . . . . . . . . . . . . . . . with syn297N, syn343G, 471H,
. . . . . . . . . . . . . . KoreaAF2411_2009_11_11
. . . . . . . . . . . . . . . . . . . with 237I, syn286K,
. . . . . . . . . . . . . . England94840077_2009_11
. . . . . . . . . . . . . . . . . . . with 259T,
. . . . . . . . . . . . . . BahrainN11892_2009_10
. . . . . . . . . . . . . . . . . . . with 208K,
. . . . . . . . . . . . . . Nevada16_2009_10_02
. . . . . . . . . . . . . . . . . . . with 464R mix wt,
. . . . . . . . . . . . . . Tasmania2005_2009_07_03
. . . . . . . . . . . . . . . . . . . with 289M,
. . . . . . . . . . . . . . Texas42303371_2009
. . . . . . . . . . . . . . . . . . . with syn456L, syn507K],
. . . . . . . . syn449Y (TAc) [H3N8 Ttc],
. . . . . . . . syn474C [H3N8])

. . . . IranKaraj5327_2010_12_06 (
. . . . . . . . syn34N [JapanKanagawa74_2010_10_16, et al],
. . . . . . . . 146G [JapanKanagawa74_2010_10_16, et al],
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn465N [OzBrisbane209_51F_2010_08_09,
. . . . . . . . . . . . . . . . . . . . with 156E & 225G,
. . . . . . . . . . . . . . CalifVRDL131_2009_12_30, et al],
. . . . . . . . syn538F [Brunei218_2010 with 188T])

Australia Sequence

. . . . OzBrisbane209_51F_2010_08_09 (
. . . . . . . . 156E [H2N3, H3N8, H5N1, H10N7],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . 225G,
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . . . . . . . . [OzVictoria670_30M_2010_11_14
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . Emergent across Australia
. . . . . . . . . . . . . . . . . . . . . during late 2010 season,
. . . . . . . . . . . . . . . Florida14_24M_2010_08_05
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . OZVictoria512_2010_07_30
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . NZChristchurch15_2010_07_12
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . India5107_2010_06_28
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . MississippiAF2474_2010_03_10
. . . . . . . . . . . . . . . . . . . . . with syn235T,
. . . . . . . . . . . . . . . FloridaAF2197_2010_03_07
. . . . . . . . . . . . . . . . . . . . . with 156T,
. . . . . . . . . . . . . . . CalifVRDL9_2010_02_09
. . . . . . . . . . . . . . . . . . . . . with syn193S,
. . . . . . . . . . . . . . . Georgia06_2010_02_05
. . . . . . . . . . . . . . . . . . . . . with syn161Y,
. . . . . . . . . . . . . . . NY4662_2010_02_03
. . . . . . . . . . . . . . . . . . . . . with 97N, syn276H, syn283Q, syn304G,
. . . . . . . . . . . . . . . TexasJMS406_2010_01_10
. . . . . . . . . . . . . . . . . . . . . with 187A, syn193S, syn283Q,
. . . . . . . . . . . . . . . TexasJMS405_2010_01_09
. . . . . . . . . . . . . . . . . . . . . with 187A, syn283Q,
. . . . . . . . . . . . . . . CalifVRDL131_2009_12_30
. . . . . . . . . . . . . . . . . . . . . with 225G, syn455Q,
. . . . . . . . . . . . . . . LouisianaAF2435_2009_11_30
. . . . . . . . . . . . . . . . . . . . . with syn13N,
. . . . . . . . . . . . . . . Vienna291_2009_11_19
. . . . . . . . . . . . . . . catOregon29573_2009_11_09
. . . . . . . . . . . . . . . . . . . . . with 226R, syn283Q,
. . . . . . . . . . . . . . . Calif_SanDiegoINS63_2009_10_26
. . . . . . . . . . . . . . . . . . . . . with syn283Q, et al],
. . . . . . . . 377K,
. . . . . . . . 454N [H7N3, H7N7, H9N2]
. . . . . . . . . . [Florida14_24M_2010_08_05
. . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . FL_Pen210_2009_11_10
. . . . . . . . . . . . . . . . . . with 225E,
. . . . . . . . . . SouthCarolina18_2009_09_16_VxX
. . . . . . . . . . . . . . . . . . with 159D, 224K,
. . . . . . . . . . Texas45131774_2009_09_13
. . . . . . . . . . . . . . . . . . with syn223V,
. . . . . . . . . . IndiaPune9355_2009_08
. . . . . . . . . . . . . . . . . . with 225G,
. . . . . . . . . . IndiaBlore236_2009_06_xL
. . . . . . . . . . . . . . . . . . with 226R, et al],
. . . . . . . . syn465N)

1. Ellis J, Galiano M, Pebody R, Lackenby A, Thompson C, Bermingham A, McLean E, Zhao H, Bolotin S, Dar O, Watson JM, Zambon M. Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010/11. Euro Surveill. 2011;16(1)

ii=19760. Available online: <a href="http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19760" target="_blank">http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19760</a>

JJackson · Jan 14, 2011

Re: UK Genetic Evaluation thread

NS1 why did you pick 106 and 3380426 as having a higher potential for vaccine escape, just curious? I note they are both on different branches of the phylogenic tree and have genetically similar sequences around them.

NS1 · Jan 15, 2011

Re: UK Genetic Evaluation thread

JJackson said:
NS1 why did you pick 106 and 3380426 as having a higher potential for vaccine escape, just curious? I note they are both on different branches of the phylogenic tree and have genetically similar sequences around them.

158E and 159K. Changes in and around this epitope of the HA have been documented as producing "Low Reactor" status across a wide geographic coverage.

UK Genetic Evaluation thread

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