2011-03-28

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).



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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