Scandinavia Accumulates Superset on Emergent 188T Background

Sequences discussed in this analysis are variously stored publicly at GenBank and at GISAID. We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GenBank and from GISAID’s EpiFlu™ Database on which this research is based. A GISAID-generated list is detailed in a linked spreadsheet for completeness in citation.

Last Updated
2011-03-29

On 2011-03-20, the Statens Serum Institut of Copenhagen, Denmark published 6 pH1N1 sequences at GenBank sampled in a time period spanning approximately 3 weeks from late December 2010 until mid January 2011. Five of the six HA sequences demonstrate the 188T of the first pH1N1 emergent nucleotide coding having a second base revision (AcT) and two of those Denmark 188T sequences additionally carry HA 225G.

Denmark120_2010_12_20 and Denmark20_2011_01_04 with 188T and 225G demonstrate ongoing transmission of a template having 6 revisions (100N, syn179L, 188T, syn338G, syn448L, 454N) that congealed during November and December across published cases in at least nine American states and in severe and fatal UK cases. The backgrounds with 188T have exhibited experimentally and practically determined Vaccine Escape, as have backgrounds carrying 225G individually. The final silent revision at HA 448L on this particular 188T template appears to correlate with RBD revisions (190G, 221L, 224K) and to revisions at known Vaccine Escape amino acid positions (158E, 159D, 188T (AcT), 225G).

• GeneWurx_UK_December_Emerging_Genetics_v6.xls
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A potentially related, contemporary sequence from Sweden was sampled one day after Denmark120_2010_12_20.  SwedenHalmstad1_23F_2010_12_21, from the adjacent European geography, is the first published on this 188T background to carry HA 230I.  The Halmstad sequence also revised at a known Vaccine Escape position to 159K.  As the 188T bearing sub-clades represent over 50% of all GISAID-published, human pH1N1 sequences between October 2010 and March 2011, the "swl" lineage appears to have widespread 188T seeding that is attractant to additional polymorphic accommodation from zoonotic sources.

Though Scandinavia is now the only published geography with the polymorphic superset of 159K, 188T, 225G and 230I on similar backgrounds, GeneWurx analysis suggests that a signal with 188T, 225G and 230I has reportable probability in Scandinavia and several other regions worldwide.  Consideration must be given to this potential template (188T, 225G, 230I) also carrying a revision from aa156 to aa159.  In a parallel, transmitting sub-clade, 189T, 225G and 230I show potential for convergence and / or expansion with 165N and / or 158E.

Polymorphism jumping appears to be occurring bi-directionally between the transmitting 189T sub-clade and the emergent 188T sub-clades.

. . . . Denmark120_2010_12_20 (
. . . . . . . . HA truncated before aa1,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T [SwedenHalmstad1_23F_2010_12_21
. . . . . . . . . . . . . . . . with 100N, 159K, 230I,
. . . . . . . . . . . . . . . . . . . . syn338G, 377K,
. . . . . . . . . . . . . . . . . . . . 454N, syn537S],
. . . . . . . . 225G mix wt,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L [UKEngland4940476_2010_12_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4880378_2010_12_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . Kentucky09_2010_11_01
. . . . . . . . . . . . . . . . . . . . with 100N, 158E, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4640543_2010_11_f
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 190G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4920303_2010_11_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland142_2010_11_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland126_2010_11
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 221L, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4860049_2010_11
. . . . . . . . . . . . . . . . . . . . with 0A, 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . syn210S, syn338G, 377K,
. . . . . . . . . . . . . . . . . . . . . . . . 454N, 528I,
. . . . . . . . . . . . . . . . Hawaii08_2010_04_12
. . . . . . . . . . . . . . . . . . . . with 159D, 269V,
. . . . . . . . . . . . . . . . . . . . . . . . 312R, 313K, 377K,
. . . . . . . . . . . . . . . . Yakutsk_EAV_2009_11_18
. . . . . . . . . . . . . . . . . . . . with syn348V,
. . . . . . . . . . . . . . . . Yaroslavl_CHMV_2009_11_10_f
. . . . . . . . . . . . . . . . . . . . with 224K, 225G, syn348V, syn542S],
. . . . . . . . 454N)

. . . . Denmark20_2011_01_04 (
. . . . . . . . HA truncated before aa1,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T [SwedenHalmstad1_23F_2010_12_21
. . . . . . . . . . . . . . . . with 100N, 159K, 230I,
. . . . . . . . . . . . . . . . . . . . syn338G, 377K,
. . . . . . . . . . . . . . . . . . . . 454N, syn537S],
. . . . . . . . 225G mix wt,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L [UKEngland4940476_2010_12_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4880378_2010_12_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . Kentucky09_2010_11_01
. . . . . . . . . . . . . . . . . . . . with 100N, 158E, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4640543_2010_11_f
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 190G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4920303_2010_11_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland142_2010_11_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland126_2010_11
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 221L, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4860049_2010_11
. . . . . . . . . . . . . . . . . . . . with 0A, 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . syn210S, syn338G, 377K,
. . . . . . . . . . . . . . . . . . . . . . . . 454N, 528I,
. . . . . . . . . . . . . . . . Hawaii08_2010_04_12
. . . . . . . . . . . . . . . . . . . . with 159D, 269V,
. . . . . . . . . . . . . . . . . . . . . . . . 312R, 313K, 377K,
. . . . . . . . . . . . . . . . Yakutsk_EAV_2009_11_18
. . . . . . . . . . . . . . . . . . . . with syn348V,
. . . . . . . . . . . . . . . . Yaroslavl_CHMV_2009_11_10_f
. . . . . . . . . . . . . . . . . . . . with 224K, 225G, syn348V, syn542S],
. . . . . . . . 454N,
. . . . . . . . syn541C)

Supporting Sequences

From GISAID database (GISAID Citation).

. . . . SwedenHalmstad1_23F_2010_12_21 (
. . . . . . . . 100N [Slovakia1625_56X_2010_03_30_xL
. . . . . . . . . . . . . . . . . . . . with 230I],
. . . . . . . . 159K [UKEngland4940476_2010_08
. . . . . . . . . . . . . . . . . . . . with 128D, 377K,
. . . . . . . . . . . . . NY3230_2010_01_25
. . . . . . . . . . . . . . . . . . . . with 100N, syn231N],
. . . . . . . . 188T,
. . . . . . . . 230I,
. . . . . . . . syn245F [RussiaBelgorod2_2010_03_15
. . . . . . . . . . . . . . . . . . . . with 158E, 225G, 230I & syn343G],
. . . . . . . . 280A [MXinDRE797_2010_TmX
. . . . . . . . . . . . . swIowa44837_1_2009_11_08_xL
. . . . . . . . . . . . . . . . . . . . with 156E, 225N, 230I & syn346G],
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S [UKEngland5040499_2010_12_f])

. . . . UKEngland142_2010_11_severe (
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L,
. . . . . . . . 454N)

. . . . UKEngland126_2010_11 (
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 221L,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L,
. . . . . . . . 454N)

. . . . UKEngland4860049_2010_11 (
. . . . . . . . 0A,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn210S,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L,
. . . . . . . . 454N,
. . . . . . . . 528I)

. . . . Hawaii08_2010_04_12
. . . . . . . . 159D mix wt,
. . . . . . . . 269V,
. . . . . . . . syn288A,
. . . . . . . . 312R,
. . . . . . . . 313K,
. . . . . . . . 377K,
. . . . . . . . syn448L [England4940476_2010_12,
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . Kentucky09_2010_11_01
. . . . . . . . . . . . . . . . . . . . with 100N, 158E, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . England4640543_2010_11_f
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 190G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . Yakutsk_EAV_2009_11_18
. . . . . . . . . . . . . . . . . . . . with syn348V,
. . . . . . . . . . . . . . . . Yaroslavl_CHMV_2009_11_10_f
. . . . . . . . . . . . . . . . . . . . with 224K, 225G, syn348V, syn542S])

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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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