2010-01-30

H5N1 Avian Polymorphism in PF11 Traveling Widely through the United States, Italy, Spain, Russia and many of the Ukraine's Neighbors

Bear in mind that these findings are preliminary and this study will be updated as research time permits.  Feel free to inspect closely for precision.

Since the TamiFlu Resistant HK2369 was published in July 2009 from a 2009-06-11 sample of a passenger from San Francisco entering Hong Kong, an increase in count and geographic distribution has been trending with what was once a rare NA polymorphism without a clear progenitor.  The NA sequence carried a G873A, GTg=>GTa, coding for a syn291V.  The sequence also carried an early version of the 206T / 225E RBD revision on HA.

In November, a Swedish sequence from GISAID and then Norway3206-3 (showing a distinctive variant coding for 225G from a post-mortem lung), appeared with the NA syn291V.  In the past month, an accelerating quantity of sequences, primarily carrying 225E, have been published from a widespread geography demonstrating movement of this silent Neuraminidase polymorphism. 

Sequences published on GenBank and GISAID show syn291V spreading thoughout the United States from an early start in New Jersey and Oklahoma (April and May respectively).  Growth occurred by early summer from an extensive base in California to North Dakota, then Texas (September) and onto a recent Kentucky sequence with the predicted HA Triple Combination of 206T / 225E / 300S, a combination that is concurrently found in Moldova, France, Turkey, Japan, Italy, Spain and the United States.  The recent domestic cat sequence from Iowa carries the syn291V suggesting effective Human to Feline transmission.

The worldwide growth is most apparent from recently published sequences.  The syn291V has now made appearances in China, Hong Kong, the UAE, England, Sweden, Norway and Greece with extensive penetration in Spain, Italy and neighbors of the Ukraine.  Latvia, Romania, Belarus, Moldova and Poland show the change.  Russia's Vector lab has demonstrated the polymorphism on Tomsk01 and Almati01.  Furthermore, the only two published human strains in the world with the adjacent RBD combination of 225E and 226R, Novgorod01 and StPetersburg5, also carry syn291V.

The evidence shows that this Neuraminidase revision is found on a number of unusual sequences, crosses geography easily and evidently crosses sub-clades having various RBD combinations with similar ease.

Until Dr. Ilaria Capua and her team at the Istituto Zooprofilattico Sperimentale delle Venezie published 2 sequences at GenBank on 2009-01-15, a clear progenitor candidate strain was not evident.  Avian H5N1 from Nigeria sampled in 2006 carries this NA syn291V and the RBD concern HA 225G.

  • HA and NA - A/chicken/Nigeria/08RS848-6/2006 (H5N1)
  • HA and NA - A/chicken/Nigeria/08RS848-8/2006 (H5N1)
Most importantly these two recent Avian H5N1 sequences are candidates as progenitors of the HA syn413K and NA syn407V cross segment linkage that is trending toward 100 sequences in ΣPF11 during the past two months.  These four obvious polymorphisms are only a subset of the current pandemic polymorphisms identified for which these Nigerian Avian H5N1 sequences may be contributors:
  • HA 225G
  • HA syn413K
  • NA syn291V
  • NA syn407V
Several of the polymorphisms in the recent Ancona, Italy deposit coincide with the Nigerian Avian H5N1  strains, 1918 and the Tinamou from Argentina in 2008.  We are inclined to review US sequences for introductions from the Nigerian Avian H5N1 and would be most appreciative of any hands on deck that would be willing to undertake a part of this retrospective exertion and make their results available to the general public.

A hearty show of gratitude from all genetics researchers is due today to the labs who worked on these sequences in Italy.  Thank you for publishing your data in a timely fashion.

Gather & Solve.

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2010-01-28

Ukraine - 100% of New Sequences with Required HA and NA on Cross-Linked Background; 225G on 6 of 11; 1918 Markers Coalesce

Cross-Linked Silent HA and NA Polymorphisms Correlated with Fatal 225G Cases in the Ukraine and Russia
  • HA:syn413K encoded from A1281G, AAa->AAg
  • NA:syn407V encoded from T1221C, GTt->GTc
 PF11 Sequences Demonstrating Cross Segment Linkage
  • Iraq8529E3  with HA 131L, 160L, 194I, 298V and syn419L (Kentucky19 and 225G Utah42)
  • Iraq8529M1 with HA 131L, 160L, 298V and syn419L (Kentucky19 and 225G Utah42)
  • Iraq8531     with HA 130E, 131L, 298V and syn419L (Kentucky19 and 225G Utah42)
  • Australia Victoria2129 with potential H5N2 inclusions and NA 454S 
  • Australia Victoria2130 with NA 454S
  • Ukraine Kyiv377 with mixture of 225D, 225G, 225N, 225S, 225T and 225A
  • Ukraine Lviv673
  • Ukraine Lviv682
  • Ukraine Cherkasy332
  • Ukraine Cherkasy333
  • Ukraine Cherkasy346
  • Ukraine Chernihiv855L with mixture of wt 225D / 225G and additional 1918 Markers (syn238E & 324I), Fatal outcome *
  • Ukraine Chernihiv856 with mixture of wt 225D / 225G , Fatal outcome *
  • Ukraine Chernihiv857 with mixture of wt 225D / 225G and additional 1918 Markers (186P, syn238E, 324I & G796A), Fatal outcome *
  • Ukraine Chernihiv858, Fatal outcome *
  • Ukraine Dnipropetrovsk260
  • Ukraine Dnipropetrovsk267
  • Ukraine Dnipropetrovsk268
  • Ukraine Dnipropetrovsk272
  • Ukraine Dnipropetrovsk273 with mixture of wt 225D and 225G
  • Ukraine Dnipropetrovsk274
  • Ukraine Dnipropetrovsk1124
  • Ukraine Dnipropetrovsk1171
  • Ukraine LvivN2 with 225G
  • Ukraine LvivN6 with 225G
  • Ukraine TernopilN10 with 225G
  • Ukraine TernopilN11 with 225G
  • Ukraine Volin226 with 225G *
  • MoldovaG120
  • MoldovaG140
  • MoldovaG181
  • MoldovaG182
  • MoldovaG191
  • HA and NA Norway2924 with mixture of wt 225D and 225G
  • HA and NA Norway3364-2
  • HA and NA CatNS7362 TamiFlu Resistant
  • HA and NA CatS1096
  • HA and NA CatS1162
  • HA and NA CatS1179
  • HA and NA CatS1181
  • HA and NA CatS1267
  • HA and NA CatS1268
  • HA and NA CatS1402
  • HA and NA CatS1501
  • HA and NA CatS1687
  • HA and NA CatS1748
  • HA and NA CatS1751
  • HA and NA CatS1761
  • HA and NA CatS1827
  • HA and NA CatS1935
  • HA and NA CatS2120 with multiple swine markers
  • HA and NA CatS2151 with swine markers and 165N (TamiFlu Resistant CatNS7632 and Russian 225G Salekhard01)
  • HA and NA Guangdong02
  • HA and NA Guangdong05
  • HA and NA SingaporeON1156
  • HA and NA Stockholm31
  • Sweden Gothenburg2 with 146G, 324I (1918) and markers found extensively in Moldova and Russia 
  • HA and NA Russia4 with syn238E and 324I (1918)
  • HA and NA Russia12 with 324I (1918)
  • HA and NA Russia14
  • HA and NA Russia19 with 324I (1918)
  • HA and NA Russia74
  • HA and NA Russia149
  • HA and NA Russia165
  • HA and NA Russia171 with 165N
  • HA and NA Russia178
  • HA and NA Russia180 with 165N, syn239P and 264G
  • HA and NA Russia190
  • HA and NA Russia191
  • HA and NA Kurgan01 with HA 214E (MoldovaG168, G176, G188) and NA mixture at 407 (Fatal 225G Abakan02) 
  • HA and NA Omsk02 
  • HA and NA Tver2969 with 225G, Fatal outcome
  • HA and NA Salekhard01 with 165N and 225G, presumptive Fatal outcome
  • HA and NA Orenburg2974 with 225N, potential Fatal outcome
  • HA and NA Perm01 with 131P, 225G and 324I, presumptive Fatal outcome
  • HA and NA NY3702
  • HA and NA NY3715
  • HA and NA NY3828
  • United States NewYork96
  • HA and NA RhodeIsland08
  • HA and NA Texas42102708
  • HA and NA Texas45072128
  • HA and NA Texas45122886
  • United States Kentucky19 from an 18 year old subject with HA 298V
  • United States Indiana20 from a 10M subject with 5 Avian H5N1 markers *
  • US Private Sequence TamiFlu Resistant  
  • United States NorthCarolina37 from a 24F subject with HA 298V
  • United States NorthCarolina44 from a 50M subject with 6 Avian H5N1 markers *
  • United States NorthCarolina46_C2     from a 39F subject with HA 298V
  • United States NorthCarolina46_C2C1 from a 39F subject with HA 298V
  • HA and NA swine/NC/34752 with 298V 
91 sequences have encircled the globe as of 2010-01-31 * with high fidelity carrying a cross-segment paired set of background markers matching and contributing to fatal cases in the Ukraine and Russia.  225G appears in 14 on this background; 225N once and 225E precisely zero.

Autopsy reports from Ukraine pandemic fatalities continue to demonstrate 225G and cross-segment linkages.  11 Sequences published from the Ukraine on 2010-01-27 covering late October to mid November 2009 show 6 225G sequences.  11 of 11 demonstrate the cross-segment linkage marker of NA syn407V.  6 of the 11 HA sequences are truncated just prior to the syn413K marker, but the 5 that do have the complete HA are a 100% match to the cross-segment marker. 

We would be quite grateful to see the missing portions of the HA segments to validate our model.  Data sparsity is an undesirable parameter when accuracy involves human life.

Incidentally, 6 225G sequences in various mixtures are found in the set of 11 with Chernihiv859 carrying the 'rrtcodon at the amino acid position 225 showing hyper-morphic behaviour like Kyiv377.  4 of those 225G sequences also fall on the cross-segment linkage background.  Chernihiv appears to be on the march to higher virulence using 1918 polymorphisms with additional revisions from the very special bird from Argentina (2008).  Chernihiv355L carries 3 1918 polymorphisms coding for 225G, syn238E and 324I in PF11 with markers from the red-winged tinamou.  Chernihiv357 goes beyond the call of duty by appropriating 5 1918 changes coding for 186P, 225G, syn238E, 324I and 252M in PF11 with markers from the red-winged tinamou.

Recall that 252M was found during July in Brasil, the first country to officially register 1,000 deaths.  Furthermore, this polymorphism was isolated there from post-mortem blood, indicating not only a fatality in the 11 year old girl, but also spread of the viral particles via the bloodstream.  HKswNS1659, a swine sequence frequently matched to PF11 genetic acquisitions, also carries the coding for 252M.

Kyiv377 from early November in the Ukraine demonstrates a level of hyper-morphic behaviour at amino acid 225 that was previously undocumented in ΣPF11, but is the natural progression of the genetic acquisition trend line on this pandemic reservoir.  Two sequences now additionally demonstrate the TamiFlu Resistant 275Y on NA, one from Spain in late November 2009 and one from the US with details stored in a private database. 

Areas covered include Texas (3), the Northeastern United States (5), Kentucky, Indiana, North Carolina (5), China (2), Singapore, Australia (2), the Ukraine (23), Moldova (5), Russia (18), Iraq (3), Norway (2), Sweden (2) and extensive penetration in Spain (17 sequences).

This particular cross linked background pattern may precurse 225G and mixtures of 225D / 225G.  The Orenburg2974 sequence from Russia carries 225N on this background.  Receptor Binding Site (RBS) changes at 225 are associated with fatality, 225G and 225N at a rate higher than 225E.

If LvivN6 is officially confirmed as a vaccine escape event, these cross-segment pairs may be surveilled as potential future effectors of vaccine efficacy failure.

If RBS revisions at Hemagglutinin amino acid 225 are, in fact, instructive of high pathogenicity, then Russia is in the FlightPath for a more virulent winter and the Ukraine has presently built a fog of miasma that appears to be capable of spreading across the globe while leading to an expected 1,000 deaths there in less than 80 days.  
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2010-01-27

UK Partial Sequences from July 2009 Show Early Start on 225G, 225E and cross-linkage marker syn413K

The UK added 50 HA sequences today to GISAID.  Exactly zero NA segments were included.  The geographically dispersed samples are dated July 2009 and demonstrate a pattern emerging in ΣPF11 at that stage that is only now being partially documented for Europe and the United States due to a continual withholding of key sequence data. 

One 225G is found, outcome unknown.

42% of the UK deposit (21 of 50) carries the Receptor Binding Domain change of 225E also found in Almaty, Kazakhstan during that timeframe.  At that time, only 13 206T/225E combinations had been cited in this pandemic.  Reporting of these UK sequences in a timely manner would have more than doubled the case counts with the RBD polymorphism and raised flags for investigative focus. 

An RBD revision emerging at this rate and being withheld from public scientific discussion is as intellectually shortsighted as the partial reporting from the US on the Duke TamiFlu Resistant cluster in October that we are only learning today also transmitted 225GTamiFlu Resistance leading to fatalities and 1918 Second Wave RBD revisions that are transmitting . . . no report?  A doubling of 225E cases with 21 instances in a major European international travel hub and no report?

These "Science for Hire" stealthy corporate practices now being employed in the public arena leave the average citizen without the information needed to make proper health decisions.  All "science" may soon come to us via PR-driven press releases.  Fabrications and crafty wording as we've seen with this pandemic may become so very honed that even sheer disinformation will be applauded as fact by the misled public.

22% of the UK deposit (11 of 50) carries the HA syn413K from the cross-linked background.  The UK count for the cross segment linking marker, NA syn407V, cannot be presented today because no Neuraminidase segments were published.  The exclusivity pattern continues with no 225E strains on the cross-linked background and the single UK 225G case from July does not fall on the cross-linked background (as expected due to the early timing of the 206T/225G pattern).

Evidence is suggestive that as the number of sequences identified on the cross-segment linkages grows, academic honesty may be trending steeply downward.  A pattern of withholding one or the other segment (HA/NA) or, more oddly, withholding only the required portion of the pairing segment is evident in more than 100 recent samples that are essential for study.  We find an 80% to 100% blanketing of one marker in some locations and a mysterious missing block of segments or, at times, the portion of the segments for the second marker?

May we please review the HA 1281 and NA 1221 for recently published sequences?

If 225G was confirmed transmitting as early as October, is correlated to fatal outcomes (50%-80%), is now documented across the globe previously and presently, was part of the Second Wave in 1918, is linked to a vaccine escape event and is correlated to the cross-segment linked background, do we need further evidence to increase surveillance and improve data transparency to the science community and the paying public?

At the end of the day, late data is demonstrating that as of July 2009 the UK was trending ahead of many European countries with 66% of this deposit (33 of 50) showing either an RBD revision or the silent HA marker for the cross-linked background.

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2010-01-22

Russia - Ten Samples Yield One 225G, One 225N, One TamiFlu Resistant and Six on the Cross-Linked Background with HA syn413K and NA syn407V

The Institute of Physical-Chemical Medicine of Moscow and Vector introduced sequences today from 10 samples into GenBank with the HA and NA segments.  The 9 samples that are dated were taken in November 2009 and perhaps are representative of ΣPF11 at that stage in Russia.  60% of the deposit today falls onto the cross-linked background with HA syn413K and NA syn407V

Tomsk08 from lung tissue is a 225G case, presumably fatal, with 131P and Russia100 carries 225N with 131P.  Russia61 is TamiFlu Resistant in typical fashion with NA 275Y.  None of the three falls on the cross linked background.

Cross Linkage Sequences

Kurgan01   with HA 214E and NA mixture at 407
Russia4      with HA syn238E (1918) and 324I (1918)
Russia12    with HA 324I (1918)
Russia19    with HA 324I (1918)
Russia171  with HA 165N
Russia180  with HA 165N, syn239P and 264G

The silent nucleotide revision coding for a syn238E on Russia4 is notable.  As you can see from the data, genetics found on the 1918 Pandemic strains have been employed from the beginning in the ΣPF11 march.  The G755A, GAg=>GAa, coding for the syn238E is seen on all 1918 sequences and WSN33.  The revision is rare within this pandemic reservoir, demonstrating odd patterning on the 11 instances. 

The silent change is found at the beginning of this pandemic in Germany and the United States in 4 sequences:

Bayern62
Regensburg01
RegensburgD6
Missouri02

And the silent change is found recently after a gap of several months in Belarus, Russia and the United States:

Russia4
Russia14
Russia191
Belarus131
Belarus220
Belarus360
Florida25

Is this re-emergence of the silent change useful to track?  If the change fell silent at the beginning, should it also fail at this moment in time?  Does the syn238E now have a background that allows synergy and conservation?  We remind the scholar this area is only slightly downstream of two major RBD positions that are volatile within this flu reservoir (225 & 226).

This viral reservoir continues to gain genetic information in a pattern trending toward 1918 sequences.  No appearance of stability has yet occurred in this particular geography and neighboring areas.



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2010-01-21

Ukraine Predictions Found in 14 Recent Catalonia Sequences; 2 Others from Spain on Cross-Linked Background

The Hospital Clinic of Spain continues a trend of providing high quality sequences representing a cross section of their general population of cases.  Today sequences from 12 samples taken from mid to late December of 2009 were published publicly at GenBank. 

The results may define a late year inflection point in ΣPF11.  A one-to-one ratio exists between sequences bearing 225E RBD changes and sequences with the cross segment linkage of HA syn413K and NA 407V.  Only two of each are present in this set of 12 sequences. 

And the 225E sequences add to a list of 12 other very recent Spanish sequences all published after 2009-11-09 that carry a combination predicted to be found if a representative sample of 100 Ukraine sequences were to be produced . . . that representative cross-section for the Ukraine has yet to be published.  Pandemic Influenza is undaunted by our failure to properly measure and this reservoir continues the genetic acquisition cycle as is evidenced by the data from Spain and countries neighboring the Ukraine. 

We expected a small count (1 to 2) of sequences in the Ukraine to have the quadruple HA combination of 2E/206T/225E/298V.  Deposits after that prediction from Spain, including this set today, demonstrate the somewhat accurate direction of that prediction and the rapid emergence of a regional sub-clade.  Though each of these 14 sequences was published with the beginning truncated, the triple combination of 206T/225E/298V is verifiable.  Catalonia/S2143 and Catalonia/S2099 enter the list from today's Spanish deposit.
  • HA CatS2143 sampled 2009-12-21
  • HA CatS2099 sampled 2009-12-14
  • HA CatS1947 sampled 2009-11-23
  • HA CatS1944 sampled 2009-11-23
  • HA CatS1835 sampled 2009-11-16
  • HA CatS1830 sampled 2009-11-13
  • HA CatS1829 sampled 2009-11-13
  • HA CatS1828 sampled 2009-11-12
  • HA CatS1761 sampled 2009-11-09
  • HA CatS1758 sampled 2009-11-09
  • HA CatS1748 sampled 2009-11-09
  • HA CatS1674 sampled 2009-11-02
  • HA CatS1672 sampled 2009-11-02
  • HA CatS1604 sampled 2009-10-26
Cross-Linked Silent HA and NA Polymorphisms Correlated with Fatal 225G Cases in the Ukraine and Russia are found on two of the sequences from today's deposit.
  • HA and NA CatS2120 with multiple swine markers
  • HA and NA CatS2151 with swine markers and 165N matching TamiFlu Resistant CatNS7632 and Russian 225G Salekhard01
These cross-linked backgrounds are transmitting in the most recent sequences that are on file.  Determining the exact relationship and ratio changes between 225E and these apparently antagonistic cross-linked backgrounds with the silent changes may be the key to understanding the acceleration and regionality of 225G emergence.

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2010-01-19

Around the World in 80 Days on a Genetic Background that Leaves 1,000 Dead in the Ukraine

I sometimes wonder if we are not 20,000 leagues under the sea?  Non?

Data is data. Data transformed becomes information. Information may then feed decision-making.  Da?

When life and death are on the line, transforming that data into information becomes critical and high priority?  Nein?

Today, the nation of the Ukraine officially registered more than 1,000 deaths from influenza viral strains. Though the daily fatality rate is not accelerating, the base rate is holding steady, in general. We expected a mid-month attainment of this fatality level based on the slight acceleration noted previously. The flattening of the daily rate brings the Ukraine death total to 1,005 on the 2010-01-19 report, two days beyond our expectation of 2010-01-17.  The Ukraine reached a fatality total in 80 days that took 175 days in the United States, a country with 6 times the population count.

In the past 80 days, five events have coincided on this small planet:
  • 1,005 citizens are on report as "swine flu" fatalities in the Ukraine.
  • 71 sequences from 11 countries (increasing daily) are documented with a genetic background similar to those fatal cases.
  • 225G has elevated from "no big mutations" to a biased, but documented 50% fatality rate (26 Deaths/52 Sequences).
  • 225G has elevated from "spontaneous" to a very high potential as a transmissible genotype.
  • 225G on LvivN6, a fatal case on the related background, is associated with a vaccine escape event.
Data that occur in similar space and time must be interpreted to determine where on the prism the light will refract, from purely coincidental to perfectly causal.  Simply labeling an item of new data as "no big mutations" and "spontaneous" without examination is careless at best and ruthless at worst.  A subjective statement made under the banner of science is certainly permissible as an educated guess, a hypothesis.  But a hypothesis must be followed by an honest gathering of data, an increasing sample size, the examination against a template and a validation of outcome.

Expectations are yet higher for a panel of experts.  Those steps and more are required prior to making ongoing comments concerning life and death. 

We are awaiting cross-reactivity results for LvivN2, TernopilN10 and TernopilN11.  We are watching for lung sample sequences from a cross section of deaths from the beginning of the pandemic to today.

Have the scholars willingly submerged themselves as a bloc of scientists so far under the sea with so little light that they cannot see the information that is forming directly in front of their eyes?  Press releases come from Public Relations personnel sitting comfortably in the Nautilus, some of whom may have long ago "graduated" from the ranks of the working scientist.  Information comes from the bench.  Let's provide the world with valid information for valid decision-making before this pandemic surges. 

If not, we may find a public unprepared because the leading minds are content to have baptised themselves under the waves of ambiguity, a rank situation allowed only when data is obfuscated and knowledge is withheld.  Who will come to the surface before another 80 days passes and leaves us with 1,000 more deaths?

Certain sub-clades within ΣPF11 are conserving particular genetic features while attaining additional swine inclusions.  That much is certain.  One of those sub-clades is forming as a potential precursor to Receptor Binding Domain polymorphisms like 225G that are associated with fatalities.  Where are the recent sequences from the Ukraine and surrounding countries?

Will we drive for actionable answers?  Or will we patiently wait and count the expirations . . .



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Fatal Ukraine Cross Segment Linkage Extends in the US, Iraq and Australia (HA syn413K and NA syn407V)

Cross-Linked Silent HA and NA Polymorphisms Correlated with Fatal 225G Cases in the Ukraine and Russia
  • HA:syn413K encoded from A1281G, AAa->AAg
  • NA:syn407V encoded from T1221C, GTt->GTc
 PF11 Sequences Demonstrating Cross Segment Linkage
  • Iraq8529E3  with HA 131L, 160L, 194I, 298V and syn419L (Kentucky19 and 225G Utah42) *
  • Iraq8529M1 with HA 131L, 160L, 298V and syn419L (Kentucky19 and 225G Utah42) *
  • Iraq8531     with HA 130E, 131L, 298V and syn419L (Kentucky19 and 225G Utah42) *
  • Australia Victoria2129 with potential H5N2 inclusions and NA 454S *
  • Australia Victoria2130 with NA 454S *
  • Ukraine Kyiv377 with mixture of 225D, 225G, 225N, 225S, 225T and 225A
  • Ukraine Lviv673
  • Ukraine Lviv682
  • Ukraine Cherkasy332
  • Ukraine Cherkasy333
  • Ukraine Cherkasy346
  • Ukraine Dnipropetrovsk260
  • Ukraine Dnipropetrovsk267
  • Ukraine Dnipropetrovsk268
  • Ukraine Dnipropetrovsk272
  • Ukraine Dnipropetrovsk273 with mixture of wt 225D and 225G
  • Ukraine Dnipropetrovsk274
  • Ukraine Dnipropetrovsk1124
  • Ukraine Dnipropetrovsk1171
  • Ukraine LvivN2
  • Ukraine LvivN6
  • Ukraine TernopilN10
  • Ukraine TernopilN11
  • MoldovaG120
  • MoldovaG140
  • MoldovaG181
  • MoldovaG182
  • MoldovaG191
  • HA and NA Norway2924 with mixture of wt 225D and 225G
  • HA and NA Norway3364-2
  • HA and NA CatNS7362 TamiFlu Resistant
  • HA and NA CatS1096
  • HA and NA CatS1162
  • HA and NA CatS1179
  • HA and NA CatS1181
  • HA and NA CatS1267
  • HA and NA CatS1268
  • HA and NA CatS1402
  • HA and NA CatS1501
  • HA and NA CatS1687
  • HA and NA CatS1748
  • HA and NA CatS1751
  • HA and NA CatS1761
  • HA and NA CatS1827
  • HA and NA CatS1935
  • HA and NA CatS2120 with multiple swine markers *
  • HA and NA CatS2151 with swine markers and 165N (TamiFlu Resistant CatNS7632 and Russian 225G Salekhard01) *
  • HA and NA Guangdong02
  • HA and NA Guangdong05
  • HA and NA SingaporeON1156
  • HA and NA Stockholm31
  • Sweden Gothenburg2 with 146G, 324I (1918) and markers found extensively in Moldova and Russia *
  • HA and NA Russia4 with syn238E and 324I (1918) *
  • HA and NA Russia12 with 324I (1918) *
  • HA and NA Russia14
  • HA and NA Russia19 with 324I (1918) *
  • HA and NA Russia74
  • HA and NA Russia149
  • HA and NA Russia165
  • HA and NA Russia171 with 165N *
  • HA and NA Russia178
  • HA and NA Russia180 with 165N, syn239P and 264G *
  • HA and NA Russia190
  • HA and NA Russia191
  • HA and NA Kurgan01 with HA 214E (MoldovaG168, G176, G188) and NA mixture at 407 (Fatal 225G Abakan02) * 
  • HA and NA Omsk02 
  • HA and NA Tver2969 with 225G, Fatal outcome
  • HA and NA Salekhard01 with 165N and 225G, presumptive Fatal outcome
  • HA and NA Orenburg2974 with 225N, potential Fatal outcome
  • HA and NA Perm01 with 131P, 225G and 324I, presumptive Fatal outcome *
  • HA and NA NY3702
  • HA and NA NY3715
  • HA and NA NY3828
  • United States NewYork96 *
  • HA and NA RhodeIsland08
  • HA and NA Texas42102708
  • HA and NA Texas45072128
  • HA and NA Texas45122886
  • United States Kentucky19 from an 18 year old subject with HA 298V *
  • US Private Sequence TamiFlu Resistant  
  • United States NorthCarolina37 from a 24F subject with HA 298V *
  • United States NorthCarolina46_C2     from a 39F subject with HA 298V *
  • United States NorthCarolina46_C2C1 from a 39F subject with HA 298V *
  • HA and NA swine/NC/34752 with 298V *
84 sequences have encircled the globe as of 2010-01-26 * with high fidelity carrying a cross-segment paired set of background markers matching and potentially contributing to fatal cases in the Ukraine and Russia. 

Recent sequences published for Australia and for Iraq demonstrate this background for the first time in those geographies.  The state of Kentucky debuts on this list and New York posts another entry for a total of 4.  Sweden increases by one.  Spain adds two from December.   Russia adds seven from November.  A swine from North Carolina in the US sample on 2009-12-14 adds one for the US.  Three human sequences from North Carolina, submitted alongside the Duke cluster, are on this background.  The TamiFlu Resistant 225G sequences from the cluster do not fall on the cross linked background demonstrating that North Carolina has two potential avenues for 225G, the transmissible cluster strain and the cross-linked background as a precursor.

Kyiv377 from early November in the Ukraine demonstrates a level of hyper-morphic behaviour at amino acid 225 that is previously undocumented in ΣPF11, but is the natural progression of the genetic acquisition trend line on this pandemic reservoir.  Two sequences now additionally demonstrate the TamiFlu Resistant 275Y on NA, one from Spain in late November 2009 and one from the US with details stored in a private database. 

Areas covered include Texas (3), the Northeastern United States (5), Kentucky, North Carolina (4), China (2), Singapore, Australia (2), the Ukraine (18), Moldova (5), Russia (18), Iraq (3), Norway (2), Sweden (2) and extensive penetration in Spain (17 sequences).

This particular cross linked background pattern may precurse 225G and mixtures of 225D / 225G.  The Orenburg2974 sequence from Russia carries 225N on this background.  Receptor Binding Site (RBS) changes at 225 are associated with fatality, 225G and 225N at a rate higher than 225E.

If LvivN6 is officially confirmed as a vaccine escape event, these cross-segment pairs may be surveilled as potential future effectors of vaccine efficacy failure.

If RBS revisions at Hemagglutinin amino acid 225 are, in fact, instructive of high pathogenicity, then Russia is in the FlightPath for a more virulent winter and the Ukraine has presently built a fog of miasma that appears to be capable of spreading across the globe while leading to an expected 1,000 deaths there in less than 80 days.

Previous Study on this Topic:
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2010-01-09

The Ukraine Trends Toward 1,000 Fatalities by Mid-January; 225 Diversity Increases

If the present daily rate of deaths continues for the short term, the Ukraine will reach 1,000 fatalities by the middle of January, approximately 75 days from the start of the flashfire.  Their official report on January 5 showed a one day increase of 100,000 new cases.  You may recall the rapidity with which this country reached 1 million infections.

The United States with a population of 300 million reached 1,000 official fatalities roughly 6 months after the initial deaths were recorded and the new viral reservoir was identified.  We remind you that the Ukraine has a population roughly one-sixth (17%) of the United States at just under 50 million citizens. 
  • 1,000 deaths from 300 million in roughly 175 days = United States
  • 1,000 deaths from   50 million in roughly   75 days = Ukraine
Perhaps some type of acceleration is presently at work.

As GeneWurx.com is tracking the emergence of Receptor Binding Site polymorphisms and epitope acquisitions in relation to published epidemiological and clinical accounts, the Ukraine continues to offer the most comprehensive picture and the most up-to-date information. Coupled with the recent publication of sequences from Russia and Turkey that correspond in various areas with the Ukraine’s early sequence deposit (225 diversity, HA syn413K and NA syn407V) and the additional interlacing of that same superset of related sequences (Ukraine, Russia, Turkey) with Spain, US and Chinese PF11 and H5N1 genetic markers, the present acceleration of cases and deaths in the Ukraine should be closely monitored.

The most recent sequences published from the Ukraine are partial and were sampled in November just as the wave reached 1 million cases.  Slightly under 4 million cases are presently reported.  4 million cases should generate more than the 23 partial sequences now published?

The most recent sample from Kiev yielded the nucleotide sequence of RVT at amino acid 225 potentially coding for 6 distinct amino acid values. R and V are Ambiguity Codes indicating mixed peaks on the sequencing trace. The R at the first base of the codon demonstrates that two values were documented. The V at the second base of the codon indicates that three distinct values were detected.

R = A and G
V = A, C and G
T = T

AAT = 225N
ACT = 225T
AGT = 225S
GAT = 225D wt
GCT = 225A
GGT = 225G

A sample from Chernihiv yielded the nucleotide sequence of RRT coding for 4 potential values at amino acid 225. The R at the first base of the codon demonstrates that two values were documented. The R at the second base of the codon indicates that the same two distinct values were detected there as well.

R = A and G
R = A and G
T = T

AAT = 225N
AGT = 225S
GAT = 225D wt
GGT = 225G

The most recent group of sequences (November) continues a strong correlation to the early cross segment linkage background and persists in accelerated genetic variation at position 225. The two sequences that demonstrate Receptor Binding Site diversity show significant single amino acid position variation on a level unprecedented in ΣPF11

Outside the RBS, this Ukraine background for presumably fatal cases appears to be strikingly stable, balancing strong genetic throw against very minimal position variation (225) arguably for immune escape and vaccine escape.  This emerging sub-clade may represent a new base point for the virus in that region, becoming a universal donor of sorts to the surrounding countries as seen in Russia and Turkey.

Just as PF11 has replaced seasonal influenza around the world, this cross segment linkage background appears to be supplanting the various versions from ΣPF11 in this region. If the cross linked silent Ukraine changes are correlated as a platform for RBS diversity at 225 and 225G/225N/225E are associated with fatality cases around the world, future fatality increases may be predictable based on the geographic extent of that cross linked background (HA syn413K and NA syn407V). 

Will the Ukraine be historically noted in some epidemiology paper of the distant future as the incubator for a new and powerful sub-clade under ΣPF11?  Is that the best we can do?  Or will we take the present trend for the full value of the data and proact today by illuminating the lab day and night with the best gear, the most definitive techniques and the brightest scholars, driving for an actionable answer?

The death count nears 1,000 in the Ukraine over a very short time span and the sequences from that country and neighboring areas indicate hyper-morphic behaviour at amino acid position 225.  No interpretation required.

Gather and Solve.

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2010-01-05

225N Increased Range and Diversity includes Texas, Argentina, Brasil, Russia and Turkey

R. Gutierrez Children's Hospital in Buenos Aires recently deposited a large group of sequences at GenBank from their winter peak of ΣPF11 activity.  Of the large group, two sequences demonstrate Receptor Binding Site changes at amino acid position 225 (June 2009) and one additional sequence is TamiFlu Resistant (late July 2009).  Not unexpectedly, none of the sequences in the large batch carry the cross-segment linkage to the Ukraine of HA syn413K and NA syn407V.

225G is represented in a sample taken 2009-06-29 (5F), Argentina/HNRG16.

275Y on the Neuraminidase conferring TamiFlu Resistance is shown on a single sample taken 2009-07-27 (1F), Argentina/HNRG23.

Of particular interest is the increasing documentation of the range and diversity of 225NArgentina/HNRG8, sampled on 2009-06-11 (2F), joins a growing list of recent quasi-species (mixtures) and samples that sequenced substantially for 225N to widen the number of backgrounds supporting this rare polymorphism to at least 5 distinct carriers.  Geographic range now includes North and South America, Russia and Turkey

Recent additions with 225N include:

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2010-01-01

HA syn413K and NA syn407V Cross Segment Linkage Increases Range and Penetration

Cross-Linked Silent HA and NA Polymorphisms Correlated with Fatal 225G Cases in the Ukraine and Russia
  • HA:syn413K encoded from A1281G, AAa->AAg
  • NA:syn407V encoded from T1221C, GTt->GTc
 PF11 Sequences Demonstrating Cross Segment Linkage
  • Iraq8529E3 *
  • Iraq8529M1 *
  • Iraq8531 *
  • Australia Victoria2129 with potential H5N2 inclusions and NA 454S *
  • Australia Victoria2130 with NA 454S *
  • Ukraine Kyiv377 with mixture of 225D, 225G, 225N, 225S, 225T and 225A
  • Ukraine Lviv673
  • Ukraine Lviv682
  • Ukraine Cherkasy332 *
  • Ukraine Cherkasy333 *
  • Ukraine Cherkasy346 *
  • Ukraine Dnipropetrovsk260 *
  • Ukraine Dnipropetrovsk267 *
  • Ukraine Dnipropetrovsk268 *
  • Ukraine Dnipropetrovsk272 *
  • Ukraine Dnipropetrovsk273 with mixture of wt 225D and 225G *
  • Ukraine Dnipropetrovsk274 *
  • Ukraine Dnipropetrovsk1124 *
  • Ukraine Dnipropetrovsk1171 *
  • Ukraine LvivN2
  • Ukraine LvivN6
  • Ukraine TernopilN10
  • Ukraine TernopilN11
  • MoldovaG120 *
  • MoldovaG140 *
  • MoldovaG181 *
  • MoldovaG182 *
  • MoldovaG191 *
  • HA and NA Norway2924 with mixture of wt 225D and 225G
  • HA and NA Norway3364-2
  • HA and NA CatNS7362 TamiFlu Resistant
  • HA and NA CatS1096
  • HA and NA CatS1162
  • HA and NA CatS1179
  • HA and NA CatS1181
  • HA and NA CatS1267
  • HA and NA CatS1268
  • HA and NA CatS1402
  • HA and NA CatS1501
  • HA and NA CatS1687
  • HA and NA CatS1748
  • HA and NA CatS1751
  • HA and NA CatS1761
  • HA and NA CatS1827
  • HA and NA CatS1935 *
  • HA and NA Guangdong02
  • HA and NA Guangdong05
  • HA and NA SingaporeON1156
  • HA and NA Stockholm31
  • HA and NA Russia14
  • HA and NA Russia19
  • HA and NA Russia74
  • HA and NA Russia165
  • HA and NA Russia178
  • HA and NA Russia190
  • HA and NA Russia191
  • HA and NA Omsk02 
  • HA and NA Tver2969 with 225G, Fatal outcome *
  • HA and NA Salekhard01 with 225G, presumptive Fatal outcome
  • HA and NA Orenburg2974 with 225N, potential Fatal outcome
  • HA and NA NY3702
  • HA and NA NY3715
  • HA and NA NY3828
  • HA and NA RhodeIsland08
  • HA and NA Texas42102708
  • HA and NA Texas45072128
  • HA and NA Texas45122886
  • US Private Sequence TamiFlu Resistant  
68 sequences have encircled the globe as of 2010-01-18 * with high fidelity carrying a cross-segment paired set of background markers matching and potentially contributing to the Ukraine fatal cases.  Kyiv377 from early November in the Ukraine demonstrates a level of hyper-morphic behaviour at amino acid 225 that is previously undocumented in ΣPF11, but is the natural progression of the genetic acquisition trend line on this pandemic reservoir.  Two sequences now additionally demonstrate the TamiFlu Resistant 275Y on NA, one from Spain in late November 2009 and one from the US with details stored in a private database. 

Moldova, a neighbor of the Ukraine, demonstrates extensive NA syn407V, but is missing the HA area for the syn413K on most sequences.  5 of 7 from Moldova with complete HA sequences display the cross segment linkage.

Expect to see many sequences from the Ukraine on this particular background when HA and NA are deposited for review as most of the recent published Hemagglutinins do carry the syn413K and the published Neuraminidase match the syn407VChernihiv452 from the Ukraine with a mixture of 225D, 225G, 225N and 225S carries the syn413K, but has no NA published.  A more comprehensive deposit of these two antigenic gene segments (HA and NA) from the Ukraine would allow a definitive conclusion.

Areas covered include Texas (3), the Northeastern United States (4), China (2), Singapore, Australia (2), the Ukraine (18),  Moldova (5), Russia (11), Iraq (3), Norway (2), Sweden and extensive penetration in Spain (15 sequences).  This particular background pattern may precurse 225G and mixtures of 225D / 225G.  If LvivN6 is officially confirmed as a vaccine escape event, these cross-segment pairs may be surveilled as potential future effectors of vaccine efficacy failure.

Publication of the remaining Neuraminidase segments for the 33 Norwegian and Japanese specimens bearing HA syn413K would allow a more precise review.  Although 9 of the recent sequences from Norway carry syn413K, none of the 225E strains from Norway have the syn413K.  The patterns are highly suggestive that all of the Norse 225G strains do.  The 2009-12-29 release of the NA for Norway2924 confirmed that previous suggestion.

The Orenburg2974 sequence from Russia also carries 225N on this background.  Bryansk2971, also from Russia with presumably fatal 225G from the lung, demonstrates the syn413K but has no entry for the Neuraminidase to confirm this cross segment linkage.

If RBS revisions at amino acid 225 are, in fact, instructive of high pathogenicity, then Russia is in the FlightPath for a more virulent winter and the Ukraine has presently built a fog of miasma that appears to be capable of spreading across the globe.

Please visit GeneWurx.com for insight into the latest published studies.

GeneWurx.com