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:

• 2010-01-01 HA syn413K and NA syn407V Cross Segment Linkage Increases Range and Penetration
• 2009-12-04 Spain Introduces 2 November Sequences with Cross-Segment Pairing from Fatal Cases in the Ukraine
• 2009-11-28 Ukraine and Spain Cross-Linked HA and NA Silent Changes Circle the Globe
• 2009-11-26 The Ukraine, Norway and Spain Share Paired HA and NA Changes

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

Wisconsin Virus Commits Zoonosis and Fails; Influenza Flux at Work

JCVI / the Medical College of Wisconsin submitted a set of sequences to GenBank on 2009-11-11. The sub-segment genomic variance that occurs when viral diseases commit zoonosis is demonstrated. We’ve discussed the coinage, Influenza Flux, in the past.  One particular Wisconsin sequence provides a useful discussion point for the sub-segment, bidirectional influx / reflux (emergence / reversion) of genetic material between distinct species-adapted, viral reservoirs.

• A/Wisconsin/629-D00117, sampled 2009-05-28, from a 3Y
• A/Wisconsin/629-D01058, sampled 2009-05-04, from a 7Y

WiscD0117 considered alongside WiscD1058 may demonstrate with simplicity an observable situation early in the pandemic where a viral reservoir attempted species-specific (human) adaptation and failed. Documenting the reservoir’s failures to adapt may be as important to future scholars as analysing the path of beneficial adaptation within the zoonosis to humans.

The two Hemagglutinins are homologous, but for a single silent nucleotide variance. WiscD1058 is identical to Canadian sequences (2) to the immediate north and Mexican sequences (2) on the same continent to the distant south.  WiscD0117 from the 3 year old, however, stands alone at the nucleotide level though matching hundreds of PF11 sequences at the amino acid coding.

A silent SNP at the third base codon, A592G, sets this sequence as novel within ΣPF11 even today (5 months later), revising “CTa -> CTg” and coding for a synonymous Leucine at residue 179, (syn179L). The A592G SNP appears at GenBank within A/swine/Hong Kong/1110/2006 of serotype H1N2.

We widened the input series for a geographic match and temporal proximity to enhance the results.

Influenza Flux Dataset
Samples Selected for Evaluation
Samples in purple show 100% Homology

A/Mexico/InDRE13551, sampled 2009-04-28
A/Mexico/InDRE13555, sampled 2009-04-29
A/Wisconsin/629-D01058, sampled 2009-05-04
A/Canada-PQ/RV1758, sampled 2009-05-08
A/Canada-QC/RV1954, sampled 2009-05-17
A/Wisconsin/629-D00117, sampled 2009-05-28
A/Wisconsin/629-D00829, sampled 2009-05-28 (324I)
A/Wisconsin/629-D01026, sampled 2009-05-28
A/Wisconsin/629-D01083, sampled 2009-05-28 (252L)
A/Wisconsin/629-D02144, sampled 2009-05-28 (324I, identical to WiscD0829)
A/Wisconsin/629-D00223, sampled 2009-05-30 (159T)
A/Wisconsin/629-D02013, sampled 2009-05-30 (35I)

Note the reasonable number of data points around the WiscD0117 sequence of interest. Many of these carry independent recombinations, including 35I, 159T, 252L and 324I.  All sequences shown on the list demonstrate the wild type 592A, except WiscD0117, including the two sequences that were sampled AFTER the original A592G SNP. 

Either an attractant signal was very strong to revert the silent SNP in the subsequent Wisconsin samples or the SNP was never transmitted.  In either case, ΣPF11 tried a new identity and then determined that the previous genetic footprint was more suitable.

Wisconsin is an area of interest for our evaluations due to the unusual clinical presentations and outcomes.  Influenza Flux may be more strongly driven in Wisconsin and causality must be determined.  ΣPF11 is on record as attempting new permutations in this geography, fixing them when useful like 324I from 1918 and discarding them like the syn179L when unneeded.

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Wisconsin Samples from May Match Chinese Lishui01 at HA 324I

Wisconsin adds 3 sequences to the rare HA 324I reservoir discussed earlier in the Chinese Lishui01.  The samples were taken within 48 hours of each other and all come from young subjects.  324I is found on 2008 and 2009 Seasonal H1N1 backgrounds as well as early H1N1 sequences, 1918 and WSN33.

• A/Wisconsin/629-D02144 sampled 2009-05-28 from a 17 year old subject
• A/Wisconsin/629-D01833 sampled 2009-05-27 from a 27 year old subject
• A/Wisconsin/629-D00829 sampled 2009-05-28 from a 10 year old subject

324I is now found on 13 wt specimens at GenBank.

• United States (8)
• Japan (4)
• China (1)

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China - Lishui01 PF11 Carries Human-Fit Seasonal Marker at 324

A/Lishui/01/2009 from July 2009 appears to be the first Chinese PF11 sample to carry the robust signal of 324I on HA, a human-fit polymorphism carried on Seasonal H1N1 2008 and 2009 backgrounds as well as 1918 specimens. 

The Lishui HA also shows the rare PF11 226R.  The recent ZhejiangDTID-ZJU01, Ekaterinburg01 and Finland553 carry this polymorphism that profiled early within ΣPF11 in one Texas and two Mexico samples.

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