2013-03-04

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, (pH1N1υ).  Four of the seven severe cases demonstrate antigenic variation.  Twelve of the seventeen Clade2:188T HA fragments carry pH1N1υ polymorphisms, a significant rate of Clade Crossing.  60% of the NA Polymorphisms from this deposit are found within the pH1N1υ 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 (pH1N1Ω) 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 [pH1N1υ],
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 237I,
. . . . . . . . syn239P (CCa) [pH1N1υ],
. . . . . . . . 286E,
. . . . . . . . syn308K (AAg),
. . . . . . . . syn333F (TTc),
. . . . . . . . syn338G (GGc),
. . . . . . . . syn372Q (CAa) [pH1N1υ],
. . . . . . . . 377K,
. . . . . . . . syn396V (GTg),
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N,
. . . . . . . . 502K [pH1N1υ],
. . . . . . . . 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) [pH1N1υ],
. . . . . . . . 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) [pH1N1υ],
. . . . . . . . syn179L (CTg) [H5N1],
. . . . . . . . 188T [avH1N1, H5N1],
. . . . . . . . syn215P (CCa) [avH1N1, H5N1],
. . . . . . . . 237I [avH1N1, H5N1 LookAsideupstream wt, H10],
. . . . . . . . syn239P (CCa) [pH1N1υ],
. . . . . . . . 286E [H6N1],
. . . . . . . . syn308K (AAg) [avH1N1, H5N1],
. . . . . . . . syn333F (TTc) [avH1N1, H5N1],
. . . . . . . . syn337A (GCt) [pH1N1υ syn],
. . . . . . . . syn338G (GGc) [avH1N1, H5N1],
. . . . . . . . syn372Q (CAa) [pH1N1υ],
. . . . . . . . 377K [pH1N1υ],
. . . . . . . . syn396V (GTg) [avH1N1, H5N1 syn],
. . . . . . . . syn417G (GGg) [avH1N1, H5N1],
. . . . . . . . syn448L (TTg) [pH1N1υ],
. . . . . . . . 454N [pH1N1υ],
. . . . . . . . 477M [pH1N1 avian],
. . . . . . . . 502K [pH1N1υ],
. . . . . . . . HA Truncated after aa508)

. . . . SpainCatalonia5925S_29F_2013_02_05 (
. . . . . . . . GISAID NA EPI427228
. . . . . . . . 14 Polymorphisms (5 Amino and 9 Silent)
. . . . . . . . NA Truncated before aa35,
. . . . . . . . 44S [pH1N1υ],
. . . . . . . . 106V [pH1N1υ],
. . . . . . . . syn176S (TCg) [pH1N1υ],
. . . . . . . . 200S [avH1N1, H5N1],
. . . . . . . . syn205V (GTa)  [avH1N1, H5N1],
. . . . . . . . syn209N (AAt) [pH1N1υ],
. . . . . . . . syn228E (GAa)  [avH1N1, H5N1],
. . . . . . . . syn240T (ACc) [pH1N1υ],
. . . . . . . . 241I [pH1N1υ],
. . . . . . . . syn264V (GTt) [avH1N1, H5N1],
. . . . . . . . 369K [pH1N1υ],
. . . . . . . . syn377P (CCa) [pH1N1υ],
. . . . . . . . syn378N (AAt) [avH1N1, H5N1],
. . . . . . . . syn393I (ATt) [pH1N1υ],
. . . . . . . . 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 [pH1N1υ],
. . . . . . . . 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 [pH1N1υ],
. . . . . . . . 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 [pH1N1υ],
. . . . . . . . 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) [pH1N1υ],
. . . . . . . . 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) [pH1N1υ],
. . . . . . . . 286E,
. . . . . . . . syn308K (AAg),
. . . . . . . . syn329S (TCc) [pH1N1υ],
. . . . . . . . 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) [pH1N1υ],
. . . . . . . . 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) [pH1N1υ syn],
. . . . . . . . syn122K (AAa),
. . . . . . . . syn127P (CCa),
. . . . . . . . 146G,
. . . . . . . . 166I,
. . . . . . . . syn171D (GAc),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn258F (TTt),
. . . . . . . . syn275V (GTt) [pH1N1υ],
. . . . . . . . syn337A (GCt) [pH1N1υ 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) [pH1N1υ],
. . . . . . . . syn258F (TTt),
. . . . . . . . syn275V (GTt) [pH1N1υ],
. . . . . . . . syn337A (GCt) [pH1N1υ 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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