Prediction Demonstrated in USA of Triple Polymorphism pH1N1 HA 166N, 188T & 189T

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 Excel for completeness in citation.

Publish Date : 2013-11-28
Last Update : 2013-11-29

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1 Predicted Sequence

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The United States CDC published a sequence on 2013-09-09 with Clade Crossing evidence sampled on 2013-08-13 from a 57 year old male in Indiana.  This Indiana22_C2_57M_2013_08_13 sequence fulfills the triple polymorphism genetic change and timing of the prediction published on 2013-02-26 titled HA 166N Polymorphism Potential on pH1N1 Cross-Clade Background with Both 188T and 189T.

No clinical progression, treatment annotation or clinical outcome has yet been published corresponding to this very important case that originated from the Indiana State Department of Health Laboratories.

HA Polymorphisms

. . . . Indiana22_C2_57M_2013_08_13 (

. . . . . . . . A/Indiana/22/2013
. . . . . . . . H7N9 Correlation NA 94I
. . . . . . . . Host Transition Indication NA 94I
. . . . . . . . CrossClade 188T and 189T
. . . . . . . . GISAID HA EPI467365

. . . . . . . . GISAID Isolate EPI_ISL_145658

. . . . . . . . 20 Polymorphisms (9 Amino and 11 Silent)

. . . . . . . . syn#4Y (TAc),

. . . . . . . . syn77S (AGt),

. . . . . . . . 100N,

. . . . . . . . 166N,

. . . . . . . . syn174K (AAg),

. . . . . . . . syn179L (CTg),

. . . . . . . . 188T,

. . . . . . . . 189T,

. . . . . . . . 237I,

. . . . . . . . 286E,

. . . . . . . . syn308K (AAg),

. . . . . . . . syn333F (TTc),

. . . . . . . . syn338G (GGc),

. . . . . . . . syn372Q (CAa),

. . . . . . . . 377K,

. . . . . . . . syn396V (GTg),

. . . . . . . . syn448L (TTg),

. . . . . . . . 454N,

. . . . . . . . syn500R (AGg) [pH1N1 Rare],

. . . . . . . . . . . . . . . . . . [H7N9 Avian],

. . . . . . . . 502K)

NA Polymorphisms

. . . . Indiana22_C2_57M_2013_08_13 (

. . . . . . . . A/Indiana/22/2013
. . . . . . . . H7N9 Correlation NA 94I
. . . . . . . . Host Transition Indication NA 94I
. . . . . . . . CrossClade 188T and 208K
. . . . . . . . GISAID NA EPI467364

. . . . . . . . GISAID Isolate EPI_ISL_145658

. . . . . . . . 14 Polymorphisms (6 Amino and 8 Silent)

. . . . . . . . 44S,

. . . . . . . . 94I [pH1N1 Rare:
. . . . . . . . . . . . . 10(9) Cases over 10 Sequences,
. . . . . . . . . . . . . . . . . 2013 - Count 02
. . . . . . . . . . . . . . . . . 2012 - Count 02
. . . . . . . . . . . . . . . . . 2011 - Count 00
. . . . . . . . . . . . . . . . . 2010 - Count 04
. . . . . . . . . . . . . . . . . 2009 - Count 02],
. . . . . . . . . . [Emergent H7N9 wild type],
. . . . . . . . . . [Host Transition Indication:
. . . . . . . . . . . . . H7N1 Passerine Starling England,
. . . . . . . . . . . . . H7N1 Parrot Ireland,
. . . . . . . . . . . . . H7N1 Ostrich South Africa],

. . . . . . . . . . [H5N1 China Human wild type],
. . . . . . . . . . [s2007 H1N1],
. . . . . . . . 106V,

. . . . . . . . syn156R (CGg),

. . . . . . . . syn176S (TCg),

. . . . . . . . 200S [H5N1],

. . . . . . . . syn205V (GTa) [Emergent H7N9 wild type],
. . . . . . . . . . . . . . . . . . [avH1N1_farm],
. . . . . . . . . . . . . . . . . . [H5N1 wild type],
. . . . . . . . . . . . . . . . . . [H6N1],

. . . . . . . . syn209N (AAt) [H5N1 wild type],

. . . . . . . . syn240T (ACc),

. . . . . . . . 241I [H5N1],

. . . . . . . . syn243T (ACt) [H5N1 China Human wild type],

. . . . . . . . . . . . . . . . . . [H7N9 Avian],

. . . . . . . . 369K,

. . . . . . . . syn377P (CCa) [H5N1 wild type],

. . . . . . . . syn378N (AAt) [H5N1 wild type])

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pH1N1 Influenza Hemagglutinin & Neuraminidase Segments elucidated at 2013-09-10-23_00_00_621110 by GeneWurx see.PolyDetector v0, Copyright 2007-2013.

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High-CFR Clade1.Upsilon Markers Cross to pH1N1.Clade2 on 70% of Spain's Recent pH1N1 Hospitalisations

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 PDF for completeness in citation.

Publish Date : 2013-03-04
Last Update : 2013-03-08

The most widespread Pandemic Influenza H1N1 clade is actively inheriting virulence factors from the most dangerous sub-clade (Upsilon with a minimum 5% Fatality Rate).  Friday’s genetic sequences from Spain confirmed our predictions of further spread from the highest fatality sub-clade onto the widest circulating strain.  This batch of sequences also shows significant inclusion of antigen donations at the nucleotide level from recent H5N1 Avian Influenza.

Spain’s 2013-03-01 GISAID pH1N1 deposit of 17 HA Fragments and 3 NA Fragments from 2013 cases carries 258 polymorphisms from the pH1N1 Origin Reference.  61 Distinct Polymorphisms appear among the HA fragments and 15 across the NA fragments.  All sequences are on a Clade2:188T background.

Five of the seven severe cases (70%) involve Clade Crossing with Clade1.Upsilon, (pH1N1_υ).  Four of the seven severe cases demonstrate antigenic variation.  Twelve of the seventeen Clade2:188T HA fragments carry pH1N1_υ polymorphisms, a significant rate of Clade Crossing.  60% of the NA Polymorphisms from this deposit are found within the pH1N1_υ NA subset.

• Hemagglutinin – Average 13.0 polymorphisms Per Fragment
• Neuraminidase – Average 12.3 polymorphisms Per Fragment

Hypermorphic behaviour with a tendency toward homology with H5N1 and Avian H1N1 continues to be present in the development toward a future state of Pandemic H1N1 Omega (pH1N1_Ω) as demonstrated in SpainCatalonia5925S_29F_2013_02_05 [EPI427227] from a 29 year old female with 36 combined polymorphisms (22 HA / 14 NA) though both gene segments are fragments.

Please refer to the GeneWurx PolyPlus PhyloGenetic tree for a rapid assessment of details concerning sequence relationships, passage history, age, gender, clinical outcome and individual polymorphisms (amino and 'silent').

The SpainGalicia207_M_6mF_2013_01_25_s [EPI427246] disease that hospitalised a 6 month old baby girl at the end of January  carries an HA 166N change that we have predicted to translate onto a lower branch of the tree that is annotated with ‘75A, 176I, 189T’.  Further severity is expected in babies and young children infected with the predicted strain.

HA and NA Polymorphisms by Sequence

. . . . SpainCatalonia2076930NS_59M_2013_02_18 (

. . . . . . . . GISAID HA EPI427229

. . . . . . . . 18 Polymorphisms (8 Amino and 10 Silent)

. . . . . . . . HA Truncated before aa11,

. . . . . . . . syn39K (AAa),

. . . . . . . . syn77S (AGt),

. . . . . . . . 100N,

. . . . . . . . 144T [pH1N1_υ],

. . . . . . . . syn179L (CTg),

. . . . . . . . 188T,

. . . . . . . . 237I,

. . . . . . . . syn239P (CCa) [pH1N1_υ],

. . . . . . . . 286E,

. . . . . . . . syn308K (AAg),

. . . . . . . . syn333F (TTc),

. . . . . . . . syn338G (GGc),

. . . . . . . . syn372Q (CAa) [pH1N1_υ],

. . . . . . . . 377K,

. . . . . . . . syn396V (GTg),

. . . . . . . . syn448L (TTg),

. . . . . . . . 454N,

. . . . . . . . 502K [pH1N1_υ],

. . . . . . . . HA Truncated after aa541)

. . . . SpainCatalonia2076930NS_59M_2013_02_18 (

. . . . . . . . GISAID NA EPI427230

. . . . . . . . 12 Polymorphisms (6 Amino and 6 Silent)

. . . . . . . . NA Truncated before aa35,

. . . . . . . . 44S,

. . . . . . . . 52N,

. . . . . . . . 106V,

. . . . . . . . syn176S (TCg),

. . . . . . . . 200S,

. . . . . . . . syn205V (GTa),

. . . . . . . . syn209N (AAt),

. . . . . . . . syn240T (ACc),

. . . . . . . . 241I,

. . . . . . . . 369K,

. . . . . . . . syn377P (CCa),

. . . . . . . . syn378N (AAt),

. . . . . . . . NA Truncated after aa465)

. . . . SpainMadrid196_70F_2013_02_05_s (

. . . . . . . . GISAID HA EPI427247

. . . . . . . . 12 Polymorphisms (4 Amino and 8 Silent)

. . . . . . . . HA Truncated before aa#3,

. . . . . . . . syn16T (ACg),

. . . . . . . . syn55L (TTa) [pH1N1_υ],

. . . . . . . . syn77S (AGt),

. . . . . . . . 100N,

. . . . . . . . syn162P (CCt),

. . . . . . . . syn179L (CTg),

. . . . . . . . 188T,

. . . . . . . . 237I,

. . . . . . . . 286E,

. . . . . . . . syn308K (AAg),

. . . . . . . . syn333F (TTc),

. . . . . . . . syn338G (GGc),

. . . . . . . . HA Truncated after aa342)

. . . . SpainCatalonia5925S_29F_2013_02_05 (

. . . . . . . . GISAID HA EPI427227

. . . . . . . . 22 Polymorphisms (8 Amino and 14 Silent)

. . . . . . . . HA Truncated before aa11,

. . . . . . . . syn39K (AAa) [avH7, avH10],

. . . . . . . . syn77S (AGt) [avH1N1, H5N1 syn],

. . . . . . . . 100N [avH1N1, H5N1],

. . . . . . . . syn158G (GGg) [pH1N1_υ],

. . . . . . . . syn179L (CTg) [H5N1],

. . . . . . . . 188T [avH1N1, H5N1],

. . . . . . . . syn215P (CCa) [avH1N1, H5N1],

. . . . . . . . 237I [avH1N1, H5N1 LookAside_upstream wt, H10],

. . . . . . . . syn239P (CCa) [pH1N1_υ],

. . . . . . . . 286E [H6N1],

. . . . . . . . syn308K (AAg) [avH1N1, H5N1],

. . . . . . . . syn333F (TTc) [avH1N1, H5N1],

. . . . . . . . syn337A (GCt) [pH1N1_υ syn],

. . . . . . . . syn338G (GGc) [avH1N1, H5N1],

. . . . . . . . syn372Q (CAa) [pH1N1_υ],

. . . . . . . . 377K [pH1N1_υ],

. . . . . . . . syn396V (GTg) [avH1N1, H5N1 syn],

. . . . . . . . syn417G (GGg) [avH1N1, H5N1],

. . . . . . . . syn448L (TTg) [pH1N1_υ],

. . . . . . . . 454N [pH1N1_υ],

. . . . . . . . 477M [pH1N1 avian],

. . . . . . . . 502K [pH1N1_υ],

. . . . . . . . HA Truncated after aa508)

. . . . SpainCatalonia5925S_29F_2013_02_05 (

. . . . . . . . GISAID NA EPI427228

. . . . . . . . 14 Polymorphisms (5 Amino and 9 Silent)

. . . . . . . . NA Truncated before aa35,

. . . . . . . . 44S [pH1N1_υ],

. . . . . . . . 106V [pH1N1_υ],

. . . . . . . . syn176S (TCg) [pH1N1_υ],

. . . . . . . . 200S [avH1N1, H5N1],

. . . . . . . . syn205V (GTa)  [avH1N1, H5N1],

. . . . . . . . syn209N (AAt) [pH1N1_υ],

. . . . . . . . syn228E (GAa)  [avH1N1, H5N1],

. . . . . . . . syn240T (ACc) [pH1N1_υ],

. . . . . . . . 241I [pH1N1_υ],

. . . . . . . . syn264V (GTt) [avH1N1, H5N1],

. . . . . . . . 369K [pH1N1_υ],

. . . . . . . . syn377P (CCa) [pH1N1_υ],

. . . . . . . . syn378N (AAt) [avH1N1, H5N1],

. . . . . . . . syn393I (ATt) [pH1N1_υ],

. . . . . . . . NA Truncated after aa462)

. . . . SpainNavarra193_15F_2013_02_04 (

. . . . . . . . GISAID HA EPI427248

. . . . . . . . 13 Polymorphisms (7 Amino and 6 Silent)

. . . . . . . . HA Truncated before aa#10,

. . . . . . . . syn#4Y (TAc),

. . . . . . . . 75A,

. . . . . . . . syn77S (AGt),

. . . . . . . . 100N,

. . . . . . . . 176I,

. . . . . . . . syn179L (CTg),

. . . . . . . . 188T,

. . . . . . . . 189T [pH1N1_υ],

. . . . . . . . 237I,

. . . . . . . . 286E,

. . . . . . . . syn308K (AAg),

. . . . . . . . syn333F (TTc),

. . . . . . . . syn338G (GGc),

. . . . . . . . HA Truncated after aa345)

. . . . SpainMurcia165_39F_2013_01_30_s (

. . . . . . . . GISAID HA EPI427252

. . . . . . . . 13 Polymorphisms (8 Amino and 5 Silent)

. . . . . . . . HA Truncated before aa27,

. . . . . . . . 75A,

. . . . . . . . syn77S (AGt),

. . . . . . . . 89N,

. . . . . . . . 100N,

. . . . . . . . 176I,

. . . . . . . . syn179L (CTg),

. . . . . . . . 188T,

. . . . . . . . 189T [pH1N1_υ],

. . . . . . . . 237I,

. . . . . . . . 286E,

. . . . . . . . syn308K (AAg),

. . . . . . . . syn333F (TTc),

. . . . . . . . syn338G (GGc),

. . . . . . . . HA Truncated after aa344)

. . . . SpainMurcia164_80F_2013_01_30_s (

. . . . . . . . GISAID HA EPI427242

. . . . . . . . 14 Polymorphisms (9 Amino and 5 Silent)

. . . . . . . . HA Truncated before aa3,

. . . . . . . . 75A,

. . . . . . . . syn77S (AGt),

. . . . . . . . 89N,

. . . . . . . . 100N,

. . . . . . . . 132S,

. . . . . . . . 176I,

. . . . . . . . syn179L (CTg),

. . . . . . . . 188T,

. . . . . . . . 189T [pH1N1_υ],

. . . . . . . . 237I,

. . . . . . . . 286E,

. . . . . . . . syn308K (AAg),

. . . . . . . . syn333F (TTc),

. . . . . . . . syn338G (GGc),

. . . . . . . . HA Truncated after aa346)

. . . . SpainPaisVasco187_M_42F_2013_01_29 (

. . . . . . . . GISAID HA EPI427251

. . . . . . . . 12 Polymorphisms (4 Amino and 8 Silent)

. . . . . . . . HA Truncated before aa#9,

. . . . . . . . syn#4Y (TAc),

. . . . . . . . syn39K (AAa),

. . . . . . . . syn77S (AGt),

. . . . . . . . 100N,

. . . . . . . . syn179L (CTg),

. . . . . . . . 188T,

. . . . . . . . 237I,

. . . . . . . . syn239P (CCa) [pH1N1_υ],

. . . . . . . . 286E,

. . . . . . . . syn308K (AAg),

. . . . . . . . syn333F (TTc),

. . . . . . . . syn338G (GGc),

. . . . . . . . HA Truncated after aa344)

. . . . SpainPaisVasco185_M_38M_2013_01_29 (

. . . . . . . . GISAID HA EPI427250

. . . . . . . . 10 Polymorphisms (4 Amino and 6 Silent)

. . . . . . . . HA Truncated before aa1,

. . . . . . . . syn77S (AGt),

. . . . . . . . 100N,

. . . . . . . . syn140P (CCc),

. . . . . . . . syn179L (CTg),

. . . . . . . . 188T,

. . . . . . . . 237I,

. . . . . . . . 286E,

. . . . . . . . syn308K (AAg),

. . . . . . . . syn333F (TTc),

. . . . . . . . syn338G (GGc),

. . . . . . . . HA Truncated after aa344)

. . . . SpainGalicia208_5M_2013_01_29_s (

. . . . . . . . GISAID HA EPI427245

. . . . . . . . 12 Polymorphisms (4 Amino and 8 Silent)

. . . . . . . . HA Truncated before aa27,

. . . . . . . . syn39K (AAa),

. . . . . . . . syn77S (AGt),

. . . . . . . . 100N,

. . . . . . . . syn179L (CTg),

. . . . . . . . 188T,

. . . . . . . . 237I,

. . . . . . . . syn239P (CCa) [pH1N1_υ],

. . . . . . . . 286E,

. . . . . . . . syn308K (AAg),

. . . . . . . . syn329S (TCc) [pH1N1_υ],

. . . . . . . . syn333F (TTc),

. . . . . . . . syn338G (GGc),

. . . . . . . . HA Truncated after aa346)

. . . . SpainBaleares168_58M_2013_01_29_s (

. . . . . . . . GISAID HA EPI427244

. . . . . . . . 11 Polymorphisms (4 Amino and 7 Silent)

. . . . . . . . HA Truncated before aa5,

. . . . . . . . syn16T (ACg),

. . . . . . . . syn77S (AGt),

. . . . . . . . 100N,

. . . . . . . . syn162P (CCt),

. . . . . . . . syn179L (CTg),

. . . . . . . . 188T,

. . . . . . . . 237I,

. . . . . . . . 286E,

. . . . . . . . syn308K (AAg),

. . . . . . . . syn333F (TTc),

. . . . . . . . syn338G (GGc),

. . . . . . . . HA Truncated after aa346)

. . . . SpainPaisVasco184_M_4mM_2013_01_28 (

. . . . . . . . GISAID HA EPI427249

. . . . . . . . 10 Polymorphisms (4 Amino and 6 Silent)

. . . . . . . . HA Truncated before aa1,

. . . . . . . . syn64I (ATa),

. . . . . . . . syn77S (AGt),

. . . . . . . . 100N,

. . . . . . . . syn179L (CTg),

. . . . . . . . 188T,

. . . . . . . . 237I,

. . . . . . . . 286E,

. . . . . . . . syn308K (AAg),

. . . . . . . . syn333F (TTc),

. . . . . . . . syn338G (GGc),

. . . . . . . . HA Truncated after aa344)

. . . . SpainGalicia207_M_6mF_2013_01_25_s (

. . . . . . . . GISAID HA EPI427246

. . . . . . . . 15 Polymorphisms (5 Amino and 10 Silent)

. . . . . . . . HA Truncated before aa#3,

. . . . . . . . syn34N (AAt),

. . . . . . . . syn53L (TTa),

. . . . . . . . syn56G (GGa),

. . . . . . . . 146G,

. . . . . . . . syn150N (AAc),

. . . . . . . . 166N,

. . . . . . . . 188T,

. . . . . . . . syn190D (GAt),

. . . . . . . . syn196Q (CAa),

. . . . . . . . 200T,

. . . . . . . . syn236L (CTg),

. . . . . . . . 274T,

. . . . . . . . syn293L (CTa),

. . . . . . . . syn309Y (TAc),

. . . . . . . . syn338G (GGc),

. . . . . . . . HA Truncated after aa346)

. . . . SpainBaleares167_3M_2013_01_25 (

. . . . . . . . GISAID HA EPI427243

. . . . . . . . 12 Polymorphisms (4 Amino and 8 Silent)

. . . . . . . . HA Truncated before aa#3,

. . . . . . . . syn39K (AAa),

. . . . . . . . syn77S (AGt),

. . . . . . . . 100N,

. . . . . . . . syn179L (CTg),

. . . . . . . . 188T,

. . . . . . . . syn212K (AAa),

. . . . . . . . 237I,

. . . . . . . . syn239P (CCa) [pH1N1_υ],

. . . . . . . . 286E,

. . . . . . . . syn308K (AAg),

. . . . . . . . syn333F (TTc),

. . . . . . . . syn338G (GGc),

. . . . . . . . HA Truncated after aa344)

. . . . SpainBaleares167_3M_2013_01_25 (

. . . . . . . . GISAID NA EPI427285

. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)

. . . . . . . . 44S,

. . . . . . . . 106V,

. . . . . . . . syn176S (TCg),

. . . . . . . . 200S,

. . . . . . . . syn205V (GTa),

. . . . . . . . syn209N (AAt),

. . . . . . . . syn240T (ACc),

. . . . . . . . 241I,

. . . . . . . . 369K,

. . . . . . . . syn377P (CCa),

. . . . . . . . syn378N (AAt),

. . . . . . . . NA Truncated after aa462)

. . . . SpainPaisVasco132_M_62F_2013_01_19_s (

. . . . . . . . GISAID HA EPI427241

. . . . . . . . 14 Polymorphisms (5 Amino and 9 Silent)

. . . . . . . . HA Truncated before aa6,

. . . . . . . . syn34N (AAt),

. . . . . . . . 87G,

. . . . . . . . syn104L (tTA) [pH1N1_υ syn],

. . . . . . . . syn122K (AAa),

. . . . . . . . syn127P (CCa),

. . . . . . . . 146G,

. . . . . . . . 166I,

. . . . . . . . syn171D (GAc),

. . . . . . . . 188T,

. . . . . . . . 200T,

. . . . . . . . syn258F (TTt),

. . . . . . . . syn275V (GTt) [pH1N1_υ],

. . . . . . . . syn337A (GCt) [pH1N1_υ syn],

. . . . . . . . syn338G (GGc),

. . . . . . . . HA Truncated after aa342)

. . . . SpainPaisVasco138_M_3mM_2013_01_18 (

. . . . . . . . GISAID HA EPI427240

. . . . . . . . 14 Polymorphisms (5 Amino and 9 Silent)

. . . . . . . . HA Truncated before aa7,

. . . . . . . . syn34N (AAt),

. . . . . . . . 87G,

. . . . . . . . syn122K (AAa),

. . . . . . . . syn127P (CCa),

. . . . . . . . 146G,

. . . . . . . . 166I,

. . . . . . . . syn171D (GAc),

. . . . . . . . 188T,

. . . . . . . . 200T,

. . . . . . . . syn252V (GTa) [pH1N1_υ],

. . . . . . . . syn258F (TTt),

. . . . . . . . syn275V (GTt) [pH1N1_υ],

. . . . . . . . syn337A (GCt) [pH1N1_υ syn],

. . . . . . . . syn338G (GGc),

. . . . . . . . HA Truncated after aa342)

. . . . SpainNavarra108_M_52F_2013_01_14 (

. . . . . . . . GISAID HA EPI427239

. . . . . . . . 11 Polymorphisms (4 Amino and 7 Silent)

. . . . . . . . HA Truncated before aa#10,

. . . . . . . . syn#4Y (TAc),

. . . . . . . . syn77S (AGt),

. . . . . . . . 100N,

. . . . . . . . syn136T (ACa),

. . . . . . . . syn179L (CTg),

. . . . . . . . 188T,

. . . . . . . . 237I,

. . . . . . . . 286E,

. . . . . . . . syn308K (AAg),

. . . . . . . . syn333F (TTc),

. . . . . . . . syn338G (GGc),

. . . . . . . . HA Truncated after aa342)

. . . . SpainBaleares100_M_59F_2013_01_14 (

. . . . . . . . GISAID HA EPI427238

. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)

. . . . . . . . HA Truncated before aa2,

. . . . . . . . syn77S (AGt),

. . . . . . . . 100N,

. . . . . . . . syn179L (CTg),

. . . . . . . . 188T,

. . . . . . . . 237I,

. . . . . . . . syn262R (AGg),

. . . . . . . . 286E,

. . . . . . . . 289L,

. . . . . . . . HA Truncated after aa296)

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pH1N1 Influenza Hemagglutinin & Neuraminidase Segments elucidated at 2013-03-01-15_26_05_537900 by GeneWurx see.PolyDetector v0, Copyright 2007-2013.

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HA 189T Upsilon in Czech Republic Recombines with 188T Tau SubClade

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
2011-06-09

On 2011-06-06, the National Institute of Medical Research of the UK published 56 pH1N1 sequences at GISAID sampled in a time period spanning late 2010 to early 2011 with the geographic majority from Europe.  A subclade bearing HA 189T that is 230I-permissive gains 3 members with this deposit, but more importantly the level of polymorphic subclade jumping has accelerated as previously discussed.  The 3' end of a well-defined 188T-bearing subclade from fatal and severe cases in the UK has recombined onto the rare Upsilon subclade (53 sequences, 5.8% CFR). 

The 3 additions to pH1N1_υ are detailed, with the recombinant CzechRepublic32_xM_2011_01_18 shown first.  Though 189T has been found upon 188T backgrounds in several pandemic geographies, this 189T Czech sequence marks the first fully defined, contiguous range, triple polymorphism recombination of 188T background markers onto the 189T Upsilon subclade.

Trailing the polymorphism lists of the 3 Upsilon additions, we also detail two of the several instances of the single polymorphism HA 189T arriving on a 188T background. 

A deposit made 2011-06-05 at GenBank from Fondazione IRCCS Policlinico San Matteo in Pavia, Italy demonstrates another particular instance of subclade elasticity.  A similar crossing of the Czech pH1N1 Tau and Upsilon subclades is found in reverse on a Palermo HA segment sampled via a deep lung wash from a patient suffering Acute Respiratory Distress Syndrome (ARDS).  This 188T Tau subclade sequence, ItalyPalermo02_2011_01_31_severe, takes an 189T from Upsilon and then adds a 208K from an emerging tertiary subclade, resulting in a single 225G-bearing Italian HA segment holding data from three dominant subclades. 

These developments suggest the merit of sampling and directly sequencing a wider variety of sources and tissue types.  The investigators from Pavia have now established a working benchmark for accurately surfacing the actual causative strain sequences from severely ill patients.

On 2011-05-19, the Cantacuzino Institute of Bucharest, Romania deposited 52 sequences at GenBank, representing partial segments (several with potential 3' end recombination from non-pH1N1 primer-matching strains).  A similar adoption of HA 189T onto a known circulating 188T background occurred on RomaniaBihor51551_54F_2011_01_31 with the unusual HA 296R unique to this Romanian deposit and a single 2009 Malaysian HA.  Recall that the polymorphism HA 296H was correlated to numerous fatalities during the early pandemic in Brasil.

Co-location of these transferable components within zoonotic reservoirs provides ample opportunity for exchange.  Expectations should be reset for future pH1N1 antigenic variation as these three dominant subclades continue to demonstrate active cooperation in developing viable Vaccine Escape polymorphisms and then sharing them when perfected.

Upsilon

. . . . CzechRepublic32_xM_2011_01_18 (
. . . . . . . . GISAID HA EPI319447
. . . . . . . . 13 Polymorphisms (6 Amino and 7 Silent)
. . . . . . . . 34D,
. . . . . . . . syn87S (AGc),
. . . . . . . . syn118E (GAa),
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 218T [Texas03_M1C2_38M_2010_06_01],
. . . . . . . . . . . . . [H5N1 Egypt Human 2009],
. . . . . . . . syn287G (GGg),
. . . . . . . . syn305K (AAg),
. . . . . . . . syn346G (GGa),
. . . . . . . . 377K,
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N)

. . . . AlgeriaG388_1F_2010_12_21 (
. . . . . . . . GISAID HA EPI319430
. . . . . . . . 11 Polymorphisms (4 Amino and 7 Silent)
. . . . . . . . 34D,
. . . . . . . . syn118E (GAa),
. . . . . . . . syn158G (GGg),
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 275I,
. . . . . . . . syn287G (GGg),
. . . . . . . . syn305K (AAg),
. . . . . . . . syn346G (GGa),
. . . . . . . . syn397G (GGc))

. . . . Estonia55236_30M_2011_03_02 (
. . . . . . . . GISAID HA EPI319464
. . . . . . . . 13 Polymorphisms (5 Amino and 8 Silent)
. . . . . . . . 34D,
. . . . . . . . 42W,
. . . . . . . . syn87S (AGc),
. . . . . . . . syn118E (GAa),
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 275I,
. . . . . . . . syn287G (GGg),
. . . . . . . . syn305K (AAg),
. . . . . . . . syn346G (GGa),
. . . . . . . . syn397G (GGc),
. . . . . . . . syn469E (GAg))

Italy

. . . . ItalyPalermo02_2011_01_31_severe (
. . . . . . . . GenBank HA JN017179
. . . . . . . . BronchoAlveolar Lavage
. . . . . . . . 12 Polymorphisms (7 Amino and 5 Silent)
. . . . . . . . 100N,
. . . . . . . . syn116R (AGa),
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 189T,
. . . . . . . . 208K,
. . . . . . . . 225G,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn428L (tTG),
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N)

Romania

. . . . RomaniaBihor51551_54F_2011_01_31 (
. . . . . . . . GenBank HA CY090796
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 189T,
. . . . . . . . syn215P (CCa),
. . . . . . . . 296R [GISAID Rare 11 – Romania (10) & 2009 Malaysia],
. . . . . . . . HA Truncated after aa296)

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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
• 
  
  
  
• 
  
   

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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225E Expectation in the Ukraine

PF11 SNP geographic analysis suggests that the Ukraine cases in the next two weeks may show a very similar genetic pattern to South America in August and the Mediterranean and Adriatic FlightPath in the past 8 weeks. 

If the trend toward a higher infectivity of medical personnel continues as reported today of 687 doctors and 1,500 young specialists being ill, we would expect a higher death count in the coming days.  Between 0.5% and 1.3% of all doctors in the country are ill (by region).  Higher transmissibility is certain.

If a database of 100 sequences were to exist on the Ukraine, accurately cataloging a cross-reference of regions over 14 days of recent death and recovery cases, including major cities, rough expectations would indicate:

HA

225E
in moderate concentration (95% probability) with 206T

206T/225E/300S triplet
potential for introduction (1 sequence) (75% probability)

2E/206T/225E/298V quad combo
potential for appearance in very low count (1 to 2 sequences) (>25% probability)

2E/206T/225G/298V quad combo
potential for introduction (1 sequence) (<10% probability)

225G
potential, but certainly not widespread under current clinical reports (75% probability) with 206T

2E/206S/296H triplet
in low concentration (95% probability)

377K
potential for introduction (1 sequence) (25% probability)

270T
potential for introduction (1 sequence) (7% probability)

261V
potential for appearance in very low count (1 to 3 sequences) (>25% probability)

212 movement
potential for introduction (1 sequence) (7% probability)

208K
potential for introduction (1 sequence) (33% probability)

188/189/190 movement
potential for introduction (1 sequence) (>50% probability)

158E
potential for appearance in very low count (1 to 3 sequences) (>25% probability)

100N
potential for introduction (1 sequence) (>25% probability)

35I
potential for appearance in moderate count (<20% probability)

NA

106I, 248N pairing
potential in very low count (<20% probability)

106I, 248N, 286G triplet
potential for introduction (7% probability until the 8th week of the flashfire)

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