Avian Homology on High Diversity Sequences Distinguished Across Globe

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.

Publish Date : 2011-12-21
Last Update : 2012-01-27

On 2011-12-20, the UK National Institute of Medical Research released a group of human pH1N1 sequences at GISAID including 46 full HA and 45 full NA segments.  The sample dates cover 2010-12-15 to 2011-08-11 (44 during 2011).  Fifteen originating labs provided the samples though no specification of clinical outcome is notated within the NIMR deposit.  The cases produced 968 total polymorphisms on the Hemagglutinin and Neuraminidase gene segments (HA 638 / NA 330) averaging over 20 polymorphisms per full sequence (HA 13.9 / NA 7.3).

The superset of polymorphisms demonstrates notable non-swine, zoonotic homology according to the GeneWurx Zoonoses Listing (GZL) assessment with an 85% minimum of the 350 combined distinct HA and NA polymorphisms being found on non-swine, animal sequences (primarily avian).  Trans-Zoonotic Serotype Analyses (TZSA), [HA] / [NA], provide the detail beneath the GZL.  Additionally, GeneWurx LookAside analysis (Upstream & Downstream Distances of 1 Amino Acid each) demonstrates potential influencer relationships for pH1N1 HA polymorphisms that have not yet shown direct zoonotic homology.

The volume and span of the deposit demonstrates the ongoing significant rate of genetic acquisition onto 4 of the established clades, alongside several uncladed sequences.  Four sequences carry clade-defining elements from multiple clades.  Ambiguity in the traces is high with 44 mixed traces, 34 HA and 10 NA. 

A certain population of geographically-dispersed sequences shows a combined HA and NA total of 25 or more revisions (10 sequences, 22% of the deposit).  This deposit brings the first pH1N1 sequence with a combined 40 polymorphisms (HA and NA) on the highly avian-influenced, SenegalDakar14_1x_2011_04_14 (HA 29 / NA 11) [EPI346724].  On that Dakar HA, 23 of 29 polymorphisms (79%) are found within Avian H1N1, while at least 90% are identifiable in non-swine zoonotic reservoirs (26 of 29 HA).  This single human sequence from a very young child carries 13 amino homologies to H5N1 (9 HA / 4 NA), 13 to H9N2 (9 HA / 4 NA) and 18 to H6N1 (10 HA / 8 NA). Dakar homology to TamiFlu Resistant strains due to NA 247N is significant with 14 matches (8 HA / 6 NA).

Enhanced acquisition of avian genetic data and convergence of polymorphisms found on High-CFR and highly-zoonotic pH1N1 strains are quantified.  Variant clades appear to be gaining data from the same sources as the pH1N1 HA 230I strains (24 HA / 12 NA matches) and the Upsilon series (31 HA / 23 NA matches) of 84 sequences (5.33% CFR). 

Five countries (Cameroon, France, England, Iceland and Hungary) produced a subset of 9 sequences bearing 12 total polymorphisms within the aa156-aa159 range, a domain documented to produce Vaccine Escape.  Hungary7_xM_2011_01_31 (HA 11 / NA 06) [EPI346709] on Clade2: 188T with RBS 226R (Vaccine Match) applies polymorphic behaviour at 3 consecutive Vaccine Escape locations in this domain (HA 157E mix wt, 158E mix wt and 159D mix wt).

One sequence is TamiFlu Resistant with NA 275Y.  More importantly a strong gravity is indicated in the polymorphic pattern suggestive that more TmX due to NA 247N will be seen in the future on these types of strains.  Considering the HA and NA distinct polymorphic supersets on these human pandemic sequences, 96 (52 HA and 44 NA) changes (27%) appear on earlier pandemic sequences with TmX due to NA 247N and 85 (52 HA and 33 NA) changes (24%) appear on the subset of H5N1 sequences that carry the NA 247N marker.

Evaluating the 229 distinct HA changes derived from these 46 human pandemic sequences against fractional HA subsets of several animal serotypes, a minimum of 84% share homology.  Avian H1N1 leads the match count at 140 polymorphic values (103 Farm Avian H1N1), while H6N1 continues to participate at a significant level (88 matches).  Homology to Avian H9N2 (65), H13 (53) and the High-CFR H5N1 (104) demonstrates that this pandemic has ample opportunity for genetic input from the extant reservoirs to amplify clinical conditions.  GeneWurx LookAside analysis shows that 109 of the 229 distinct pH1N1 HA polymorphisms demonstrate an amino acid homology within 1 position upstream or downstream in a zoonotic reservoir for a total of 311 HA LookAside influencers.

Of 121 distinct NA polymorphisms, 104 are non-swine, zoonotic (86%) and a minimum of 89 are found on Avian H1N1 (74%) with 74 (61%) of those found on a subset of a dozen Farm Avian H1N1 sequences that have consistently matched polymorphisms coming onto the human H1N1 pandemic background since 2009.  NA homology with other non-swine, zoonotic reservoirs remains significant: Avian H6N1 (88 / 73%), Avian H9N2 (30) and the High-CFR H5N1 (54).

Though the zoonotic serotype backgrounds profiled against these human polymorphisms are entirely variant, these many codon-level homologies crossing multiple zoonotic reservoirs into the human pandemic illuminates the GeneWurx premise that the origin of the human H1N1 pandemic be reconsidered as avian.

Cladistics

Clade1: 189T - 07 Sequences
Clade2: 188T - 23 Sequences
Clade3: 186P - 05 Sequences
Clade5: 208K_219V - 06 Sequences

HA 638 Polymorphisms Averaging ~13.9 per Segment
NA 330 Polymorphisms Averaging ~ 7.3 per Segment

HA and NA 968 Total Polymorphisms Averaging ~20.0 across 45 w/ HA & NA

TamiFlu Resistance

One TamiFlu Resistant sequence (NA 275Y) features on a Clade2: 188T background and carries HA RBS 227G with the HA 158E (mixture with wild type) that has repeatedly been observed to promote Vaccine Escape.  Avian H1N1 carries homology with 9 of the 11 HA and 100% of NA polymorphisms on the TamiFlu Resistant French case.  One small population of Farm Avian H1N1 sequences matches on 7 of these 11 HA and 5 of 6 NA revisions.  TamiFlu Resistance Confluence (multiple TmX markers) is correlated due to 8 of the 11 HA markers sharing homology to the superset of pH1N1 NA 247N TamiFlu Resistant sequences and 100% of the NA changes.  Fourteen revisions (8 HA / 6 NA) pattern to the pH1N1 superset of HA 230I-bearing sequences.  Eleven changes (8 HA / 3 NA) equate to the High-CFR human pandemic Upsilon sub-clade.

• [EPI346699] FranceLorraine1176_50x_2011_02_23_TmX

Sequences


. . . . Madagascar9274_7M_2011_08_11 (
. . . . . . . . GISAID HA EPI346721
. . . . . . . . Clade2: 188T
. . . . . . . . 22 Polymorphisms (12 Amino and 10 Silent)
. . . . . . . . #6M,
. . . . . . . . #4C,
. . . . . . . . syn34N (AAt),
. . . . . . . . syn49G (GGa),
. . . . . . . . syn122K (AAa),
. . . . . . . . 141Q,
. . . . . . . . 146G,
. . . . . . . . 169S,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . 216G,
. . . . . . . . 259P,
. . . . . . . . syn304G (GGg),
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 388R,
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn473K (AAg),
. . . . . . . . syn512R (AGa),
. . . . . . . . syn538F (TTt),
. . . . . . . . syn546L (tTA))

. . . . Madagascar9252_23F_2011_08_10 (
. . . . . . . . GISAID HA EPI346717
. . . . . . . . 19 Polymorphisms (10 Amino and 9 Silent)
. . . . . . . . Clade2: 188T
. . . . . . . . #6M,
. . . . . . . . #4C,
. . . . . . . . syn34N (AAt),
. . . . . . . . syn49G (GGa),
. . . . . . . . syn122K (AAa),
. . . . . . . . 141Q,
. . . . . . . . 146G,
. . . . . . . . 169S,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn301I (ATa),
. . . . . . . . syn338G (GGc),
. . . . . . . . 364S,
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn473K (AAg),
. . . . . . . . syn496A (GCg),
. . . . . . . . syn538F (TTt))

. . . . Madagascar9252_23F_2011_08_10 (
. . . . . . . . GISAID NA EPI346718
. . . . . . . . 10 Polymorphisms (4 Amino and 6 Silent)
. . . . . . . . 126S,
. . . . . . . . syn152R (AGa),
. . . . . . . . syn225R (AGg),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn295N (AAt),
. . . . . . . . syn313Q (CAa),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 416N)

. . . . Madagascar8753_xF_2011_08_02 (
. . . . . . . . GISAID HA EPI346715
. . . . . . . . Clade2: 188T
. . . . . . . . 19 Polymorphisms (10 Amino and 9 Silent)
. . . . . . . . #6M,
. . . . . . . . #4C,
. . . . . . . . syn1A (GCt),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn49G (GGa),
. . . . . . . . syn122K (AAa),
. . . . . . . . 141Q,
. . . . . . . . 146G,
. . . . . . . . 169S,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 400S,
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn473K (AAg),
. . . . . . . . syn514Y (TAt),
. . . . . . . . syn538F (TTt))

. . . . Madagascar8753_xF_2011_08_02 (
. . . . . . . . GISAID NA EPI346716
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . 44S,
. . . . . . . . 56C,
. . . . . . . . 126S,
. . . . . . . . syn225R (AGg),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn295N (AAt),
. . . . . . . . syn307N (AAt),
. . . . . . . . syn313Q (CAa),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . SouthAfricaJohannesburg150_46F_2011_07_10 (
. . . . . . . . GISAID HA EPI346655
. . . . . . . . Clade5: 208K_219V
. . . . . . . . 16 Polymorphisms (8 Amino and 8 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . syn82I (ATc),
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N,
. . . . . . . . syn131S (TCa),
. . . . . . . . 141Q,
. . . . . . . . 142D,
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc),
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa),
. . . . . . . . syn512R (AGa))

. . . . SouthAfricaJohannesburg150_46F_2011_07_10 (
. . . . . . . . GISAID NA EPI346656
. . . . . . . . 9 Polymorphisms (2 Amino and 7 Silent)
. . . . . . . . syn79S (TCg),
. . . . . . . . syn89S (TCt),
. . . . . . . . syn126P (CCt),
. . . . . . . . syn229S (TCc),
. . . . . . . . syn236G (GGc),
. . . . . . . . 269I mix wt,
. . . . . . . . 299A,
. . . . . . . . syn378N (AAt),
. . . . . . . . syn405S (AGc))

. . . . CameroonLEID07111870_24F_2011_07_07 (
. . . . . . . . GISAID HA EPI346647
. . . . . . . . Clade1: 189T
. . . . . . . . 13 Polymorphisms (8 Amino and 5 Silent)
. . . . . . . . 1T,
. . . . . . . . syn168Y (TAt),
. . . . . . . . syn176V (GTt),
. . . . . . . . 189T,
. . . . . . . . 205E,
. . . . . . . . syn238E (GAa),
. . . . . . . . 275A,
. . . . . . . . syn286K (AAa),
. . . . . . . . 377K,
. . . . . . . . syn413K (AAg),
. . . . . . . . 476D,
. . . . . . . . 477K,
. . . . . . . . 523A)

. . . . CameroonLEID07111870_24F_2011_07_07 (
. . . . . . . . GISAID NA EPI346648
. . . . . . . . 4 Polymorphisms (0 Amino and 4 Silent)
. . . . . . . . syn22L (cTA),
. . . . . . . . syn135T (ACc),
. . . . . . . . syn262K (AAa),
. . . . . . . . syn398E (GAa))

. . . . SenegalDakar18_4x_2011_07_07 (
. . . . . . . . GISAID HA EPI346685
. . . . . . . . 25 Polymorphisms (8 Amino and 17 Silent)
. . . . . . . . 10H mix wt,
. . . . . . . . 35I,
. . . . . . . . 51V,
. . . . . . . . syn99I (ATt),
. . . . . . . . syn122K (AAa),
. . . . . . . . 131T,
. . . . . . . . syn152I (ATt),
. . . . . . . . syn154L (CTg),
. . . . . . . . 206S,
. . . . . . . . syn214K (AAa),
. . . . . . . . syn219I (ATt),
. . . . . . . . syn254P (CCa),
. . . . . . . . 262K,
. . . . . . . . syn276H (CAt),
. . . . . . . . syn295F (TTc),
. . . . . . . . syn301I (ATt),
. . . . . . . . syn331G (GGt),
. . . . . . . . syn337A (GCt),
. . . . . . . . syn379T (ACc),
. . . . . . . . syn433E (GAg),
. . . . . . . . syn451K (AAa),
. . . . . . . . syn456L (cTA),
. . . . . . . . 463V,
. . . . . . . . syn475D (GAc),
. . . . . . . . 523A)

. . . . SenegalDakar18_4x_2011_07_07 (
. . . . . . . . GISAID NA EPI346686
. . . . . . . . 12 Polymorphisms (5 Amino and 7 Silent)
. . . . . . . . syn20A (GCc),
. . . . . . . . 74V,
. . . . . . . . syn89S (TCt),
. . . . . . . . 106V,
. . . . . . . . syn160S (AGt),
. . . . . . . . 166I mix wt,
. . . . . . . . syn275H (CAt),
. . . . . . . . syn304V (GTt),
. . . . . . . . syn382G (GGa),
. . . . . . . . 385T,
. . . . . . . . 386K,
. . . . . . . . syn433E (GAa))

. . . . SouthAfricaJohannesburg146_xM_2011_06_29 (
. . . . . . . . GISAID HA EPI346653
. . . . . . . . Clade5: 208K_219V
. . . . . . . . 16 Polymorphisms (9 Amino and 7 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . syn75T (ACc),
. . . . . . . . syn82I (ATc),
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N,
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 218V mix wt,
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . 301V mix wt,
. . . . . . . . syn307P (CCc),
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))

. . . . SouthAfricaJohannesburg146_xM_2011_06_29 (
. . . . . . . . GISAID NA EPI346654
. . . . . . . . 8 Polymorphisms (1 Amino and 7 Silent)
. . . . . . . . syn89S (TCt),
. . . . . . . . syn126P (CCt),
. . . . . . . . syn229S (TCc),
. . . . . . . . syn236G (GGc),
. . . . . . . . 299A,
. . . . . . . . syn355N (AAc),
. . . . . . . . syn405S (AGc),
. . . . . . . . syn427I (ATt))

. . . . Madagascar3520_52M_2011_06_17 (
. . . . . . . . GISAID HA EPI346719
. . . . . . . . Clade2: 188T
. . . . . . . . 19 Polymorphisms (11 Amino and 8 Silent)
. . . . . . . . #6M,
. . . . . . . . syn34N (AAt),
. . . . . . . . syn44L (tTA),
. . . . . . . . syn122K (AAa),
. . . . . . . . 132D,
. . . . . . . . 145R,
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . 237I,
. . . . . . . . syn265G (GGg),
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 397S,
. . . . . . . . 452I,
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn496A (GCc),
. . . . . . . . syn538F (TTt))

. . . . Madagascar3520_52M_2011_06_17 (
. . . . . . . . GISAID NA EPI346720
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . 44S,
. . . . . . . . 151N mix wt,
. . . . . . . . syn177V (GTt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 339P,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn378N (AAt))

. . . . CameroonLEID06111809_33M_2011_06_16 (
. . . . . . . . GISAID HA EPI346645
. . . . . . . . Clade1: 189T
. . . . . . . . 15 Polymorphisms (10 Amino and 5 Silent)
. . . . . . . . 1T,
. . . . . . . . 189T,
. . . . . . . . syn210S (AGt),
. . . . . . . . syn238E (GAa),
. . . . . . . . 275A,
. . . . . . . . syn286K (AAa),
. . . . . . . . 377K,
. . . . . . . . syn403L (tTG),
. . . . . . . . 437I mix wt,
. . . . . . . . 439N,
. . . . . . . . syn465N (AAt),
. . . . . . . . 476D,
. . . . . . . . 477K,
. . . . . . . . 523A,
. . . . . . . . 531I)

. . . . CameroonLEID06111809_33M_2011_06_16 (
. . . . . . . . GISAID NA EPI346646
. . . . . . . . 5 Polymorphisms (1 Amino and 4 Silent)
. . . . . . . . syn22L (cTA),
. . . . . . . . syn161C (TGc),
. . . . . . . . 262R,
. . . . . . . . syn368R (AGg),
. . . . . . . . syn398E (GAa))

. . . . ThailandNonthaburi78_2011_06_08 (
. . . . . . . . GISAID HA EPI346707
. . . . . . . . Clade2: 188T
. . . . . . . . 14 Polymorphisms (8 Amino and 6 Silent)
. . . . . . . . #6M,
. . . . . . . . syn34N (AAt),
. . . . . . . . syn122K (AAa),
. . . . . . . . 146G,
. . . . . . . . syn178V (GTa),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . 218E mix wt,
. . . . . . . . 218V mix wt,
. . . . . . . . syn338G (GGc),
. . . . . . . . 375V,
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn538F (TTt))

. . . . ThailandNonthaburi78_2011_06_08 (
. . . . . . . . GISAID NA EPI346708
. . . . . . . . 9 Polymorphisms (4 Amino and 5 Silent)
. . . . . . . . syn14C (TGc),
. . . . . . . . 26T,
. . . . . . . . syn41G (GGa),
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn378N (AAt))

. . . . SouthAfricaJohannesburg128_1F_2011_06_07 (
. . . . . . . . GISAID HA EPI346651
. . . . . . . . Clade5: 208K_219V
. . . . . . . . 19 Polymorphisms (9 Amino and 10 Silent)
. . . . . . . . syn#6L (tTG),
. . . . . . . . syn47L (CTg),
. . . . . . . . 51T,
. . . . . . . . syn74S (TCt),
. . . . . . . . syn82I (ATc),
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N,
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc),
. . . . . . . . 359A,
. . . . . . . . syn366A (GCa),
. . . . . . . . 377K,
. . . . . . . . 404D,
. . . . . . . . syn446K (AAa),
. . . . . . . . syn477T (ACa))

. . . . SouthAfricaJohannesburg128_1F_2011_06_07 (
. . . . . . . . GISAID NA EPI346652
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn89S (TCt),
. . . . . . . . syn126P (CCt),
. . . . . . . . 157A mix wt,
. . . . . . . . syn163I (ATc),
. . . . . . . . syn229S (TCc),
. . . . . . . . syn236G (GGc),
. . . . . . . . syn241V (GTg),
. . . . . . . . syn298G (GGa),
. . . . . . . . 299A,
. . . . . . . . syn342G (GGg))

. . . . HongKong3960_2M_2011_04_21 (
. . . . . . . . GISAID HA EPI346726
. . . . . . . . Clade1.Upsilon (5.33% CFR)
. . . . . . . . 15 Polymorphisms (9 Amino and 6 Silent)
. . . . . . . . #12E [Novel to Upsilon],
. . . . . . . . #8I,
. . . . . . . . 34D,
. . . . . . . . syn118E (GAa),
. . . . . . . . 144E,
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 275I,
. . . . . . . . syn287G (GGg),
. . . . . . . . syn305K (AAg),
. . . . . . . . syn346G (GGa),
. . . . . . . . syn397G (GGc),
. . . . . . . . 453K,
. . . . . . . . 502K)

. . . . HongKong3960_2M_2011_04_21 (
. . . . . . . . GISAID NA EPI346727
. . . . . . . . 6 Polymorphisms (1 Amino and 5 Silent)
. . . . . . . . syn20A (GCc),
. . . . . . . . 82P,
. . . . . . . . syn139L (TTa),
. . . . . . . . syn300N (AAc),
. . . . . . . . syn327R (CGt),
. . . . . . . . syn330D (GAc))


. . . . SenegalDakar14_1x_2011_04_14 (
. . . . . . . . GISAID HA EPI346724
. . . . . . . . 29 Polymorphisms (10 Amino and 19 Silent)
. . . . . . . . 16I,
. . . . . . . . 35I [H5N1 TmX247],
. . . . . . . . 89E [H1N1 Avian],
. . . . . . . . syn99I (ATt) [H1N1 Avian],
. . . . . . . . syn122K (AAa) [H5N1 Avian],
. . . . . . . . 131T [H5N1 Avian],
. . . . . . . . syn152I (ATt),
. . . . . . . . syn154L (CTg) [H9N2 Avian],
. . . . . . . . 206S,
. . . . . . . . syn214K (AAa) [H9N2 Avian],
. . . . . . . . syn219I (ATt),
. . . . . . . . syn254P (CCa) [H9N2 Avian],
. . . . . . . . 262K [H5N1 Avian],
. . . . . . . . 266A,
. . . . . . . . syn276H (CAt) [H1N1 Avian],
. . . . . . . . syn295F (TTc) [H9N2 Avian],
. . . . . . . . syn301I (ATt),
. . . . . . . . syn331G (GGt) [H1N1 Avian],
. . . . . . . . syn337A (GCt) [H9N2 Avian],
. . . . . . . . syn338G (GGc) [H6N1 Avian],
. . . . . . . . 377K [H9N2 Avian],
. . . . . . . . syn379T (ACc) [H6N1 Avian],
. . . . . . . . syn433E (GAg) [H6N1 Avian],
. . . . . . . . syn451K (AAa) [H6N1 Avian],
. . . . . . . . syn456L (cTA) [H6N1 Avian],
. . . . . . . . 463V,
. . . . . . . . syn475D (GAc) [H6N1 Avian],
. . . . . . . . 523A [H1N1 Avian],
. . . . . . . . syn527L (TTa))

. . . . SenegalDakar14_1x_2011_04_14 (
. . . . . . . . GISAID NA EPI346725
. . . . . . . . 11 Polymorphisms (4 Amino and 7 Silent)
. . . . . . . . syn20A (GCc) [H1N1 Avian],
. . . . . . . . 74V [H1N1 Avian],
. . . . . . . . syn89S (TCt),
. . . . . . . . 106V [H1N1 Avian],
. . . . . . . . syn127L (cTG) [H1N1 Avian],
. . . . . . . . syn183A (GCc) [H1N1 Avian],
. . . . . . . . syn304V (GTt) [H1N1 Avian],
. . . . . . . . syn382G (GGa) [H1N1 Avian (Gaa)],
. . . . . . . . 385T,
. . . . . . . . 386K,
. . . . . . . . syn433E (GAa) [H1N1 Avian])

. . . . CameroonLEID04111671_1F_2011_04_12 (
. . . . . . . . GISAID HA EPI346691
. . . . . . . . Clade1: 189T
. . . . . . . . 14 Polymorphisms (9 Amino and 5 Silent)
. . . . . . . . 1T,
. . . . . . . . syn97D (GAc),
. . . . . . . . syn130D (GAt),
. . . . . . . . 155I,
. . . . . . . . 189T,
. . . . . . . . syn238E (GAa),
. . . . . . . . 275A,
. . . . . . . . syn286K (AAa),
. . . . . . . . 377K,
. . . . . . . . syn403L (tTG),
. . . . . . . . 476D,
. . . . . . . . 477K,
. . . . . . . . 509D,
. . . . . . . . 523A)

. . . . CameroonLEID04111671_1F_2011_04_12 (
. . . . . . . . GISAID NA EPI346692
. . . . . . . . 5 Polymorphisms (0 Amino and 5 Silent)
. . . . . . . . syn22L (cTA),
. . . . . . . . syn170Y (TAt),
. . . . . . . . syn262K (AAa),
. . . . . . . . syn398E (GAa),
. . . . . . . . syn421C (TGt))

. . . . SenegalDakar11_4x_2011_04_06 (
. . . . . . . . GISAID HA EPI346683
. . . . . . . . Clade3: 186P, novel sub-clade
. . . . . . . . 22 Polymorphisms (8 Amino and 14 Silent)
. . . . . . . . 12T,
. . . . . . . . 35I,
. . . . . . . . syn99I (ATt),
. . . . . . . . syn122K (AAa),
. . . . . . . . 131T,
. . . . . . . . syn152I (ATt),
. . . . . . . . syn154L (CTg),
. . . . . . . . 186P,
. . . . . . . . 206S,
. . . . . . . . syn214K (AAa),
. . . . . . . . syn219I (ATt),
. . . . . . . . syn254P (CCa),
. . . . . . . . 262K,
. . . . . . . . syn276H (CAt),
. . . . . . . . syn301I (ATt),
. . . . . . . . syn331G (GGt),
. . . . . . . . syn337A (GCt),
. . . . . . . . syn379T (ACc),
. . . . . . . . syn433E (GAg),
. . . . . . . . syn456L (cTA),
. . . . . . . . 463V,
. . . . . . . . 523A)

. . . . SenegalDakar11_4x_2011_04_06 (
. . . . . . . . GISAID NA EPI346684
. . . . . . . . 10 Polymorphisms (4 Amino and 6 Silent)
. . . . . . . . syn20A (GCc),
. . . . . . . . syn89S (TCt),
. . . . . . . . 106V,
. . . . . . . . syn172S (TCt),
. . . . . . . . 259D,
. . . . . . . . syn304V (GTt),
. . . . . . . . syn382G (GGa),
. . . . . . . . 385T,
. . . . . . . . 386K,
. . . . . . . . syn415L (tTG))

. . . . SenegalDakar09_3x_2011_03_25 (
. . . . . . . . GISAID HA EPI346703
. . . . . . . . 24 Polymorphisms (8 Amino and 16 Silent)
. . . . . . . . 35I,
. . . . . . . . 47I,
. . . . . . . . syn99I (ATt),
. . . . . . . . syn122K (AAa),
. . . . . . . . 131T,
. . . . . . . . syn152I (ATt),
. . . . . . . . syn154L (CTg),
. . . . . . . . 206S,
. . . . . . . . syn214K (AAa),
. . . . . . . . syn219I (ATt),
. . . . . . . . syn254P (CCa),
. . . . . . . . 262K,
. . . . . . . . syn276H (CAt),
. . . . . . . . syn288A (GCc),
. . . . . . . . syn301I (ATt),
. . . . . . . . syn325P (CCt),
. . . . . . . . syn331G (GGt),
. . . . . . . . syn337A (GCt),
. . . . . . . . syn379T (ACc),
. . . . . . . . syn433E (GAg),
. . . . . . . . syn456L (cTA),
. . . . . . . . 463V,
. . . . . . . . 481N,
. . . . . . . . 523A)

. . . . SenegalDakar09_3x_2011_03_25 (
. . . . . . . . GISAID NA EPI346704
. . . . . . . . 10 Polymorphisms (3 Amino and 7 Silent)
. . . . . . . . syn20A (GCc),
. . . . . . . . syn89S (TCt),
. . . . . . . . 106V,
. . . . . . . . syn281C (TGc),
. . . . . . . . syn304V (GTt),
. . . . . . . . syn370G (GGc),
. . . . . . . . syn371F (TTc),
. . . . . . . . syn382G (GGa),
. . . . . . . . 385T,
. . . . . . . . 386K)

. . . . Iceland59_xF_2011_03_24 (
. . . . . . . . GISAID HA EPI346697
. . . . . . . . Clade3: 186P
. . . . . . . . 13 Polymorphisms (6 Amino and 7 Silent)
. . . . . . . . 137T mix wt,
. . . . . . . . 144S,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg),
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V,
. . . . . . . . syn363G (GGg),
. . . . . . . . 377K,
. . . . . . . . syn455Q (CAa),
. . . . . . . . syn474C (TGt),
. . . . . . . . 482I)

. . . . Iceland59_xF_2011_03_24 (
. . . . . . . . GISAID NA EPI346698
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 46T,
. . . . . . . . syn187G (GGt),
. . . . . . . . 313R,
. . . . . . . . 321V,
. . . . . . . . 394I,
. . . . . . . . syn412L (tTA),
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)

. . . . CameroonLEID03111616_xM_2011_03_22 (
. . . . . . . . GISAID HA EPI346689
. . . . . . . . Clade1: 189T
. . . . . . . . 12 Polymorphisms (8 Amino and 4 Silent)
. . . . . . . . 1T,
. . . . . . . . 167F,
. . . . . . . . 189T,
. . . . . . . . syn238E (GAa),
. . . . . . . . 275A,
. . . . . . . . syn286K (AAa),
. . . . . . . . 377K,
. . . . . . . . syn403L (tTG),
. . . . . . . . 476D,
. . . . . . . . 477K,
. . . . . . . . 523A,
. . . . . . . . syn538F (TTt))

. . . . CameroonLEID03111616_xM_2011_03_22 (
. . . . . . . . GISAID NA EPI346690
. . . . . . . . 5 Polymorphisms (1 Amino and 4 Silent)
. . . . . . . . syn22L (cTA),
. . . . . . . . syn118R (AGa),
. . . . . . . . syn262K (AAa),
. . . . . . . . 386D,
. . . . . . . . syn398E (GAa))

. . . . FrancePaysdeLoire1347_12x_2011_03_22 (
. . . . . . . . GISAID HA EPI346701
. . . . . . . . Clade2: 188T
. . . . . . . . 12 Polymorphisms (4 Amino and 8 Silent)
. . . . . . . . 100N,
. . . . . . . . syn135V (GTg),
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn321L (cTG),
. . . . . . . . syn336I (ATc),
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn400F (TTt),
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N,
. . . . . . . . syn482V (GTt))

. . . . FrancePaysdeLoire1347_12x_2011_03_22 (
. . . . . . . . GISAID NA EPI346702
. . . . . . . . 8 Polymorphisms (2 Amino and 6 Silent)
. . . . . . . . syn162P (CCc),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn313Q (CAa),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn401G (GGg),
. . . . . . . . syn416D (GAc))

. . . . Iceland52_xM_2011_03_18 (
. . . . . . . . GISAID HA EPI346643
. . . . . . . . Clade2: 188T
. . . . . . . . 12 Polymorphisms (9 Amino and 3 Silent)
. . . . . . . . 87I,
. . . . . . . . 100N,
. . . . . . . . 158E mix wt,
. . . . . . . . 188T,
. . . . . . . . 212N mix wt,
. . . . . . . . syn304G (GGg),
. . . . . . . . syn319T (ACg),
. . . . . . . . 324I,
. . . . . . . . 377K,
. . . . . . . . 440H mix wt,
. . . . . . . . syn441H (CAt),
. . . . . . . . 454N)

. . . . Iceland52_xM_2011_03_18 (
. . . . . . . . GISAID NA EPI346644
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . UkraineDnipropetrovsk4929_21F_2011_03_10 (
. . . . . . . . GISAID HA EPI346637
. . . . . . . . Clade2: 188T
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N)

. . . . UkraineDnipropetrovsk4929_21F_2011_03_10 (
. . . . . . . . GISAID NA EPI346638
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . UkraineZaporizhzhya5200_31F_2011_03_09 (
. . . . . . . . GISAID HA EPI346663
. . . . . . . . Clade2: 188T
. . . . . . . . 10 Polymorphisms (6 Amino and 4 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 326F,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 415E,
. . . . . . . . syn441H (CAt),
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N)

. . . . UkraineZaporizhzhya5200_31F_2011_03_09 (
. . . . . . . . GISAID NA EPI346664
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 96R mix wt,
. . . . . . . . 127F,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . UkraineLuhansk5192_xF_2011_03_07 (
. . . . . . . . GISAID HA EPI346639
. . . . . . . . Clade2: 188T
. . . . . . . . . . . . crossing Clade3: 186P
. . . . . . . . 16 Polymorphisms (6 Amino and 10 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn118E (GAa),
. . . . . . . . syn130D (GAt),
. . . . . . . . 146G,
. . . . . . . . 186P mix wt,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn338G (GGc),
. . . . . . . . syn358N (Aac) mix,
. . . . . . . . syn358T mix,
. . . . . . . . 377K,
. . . . . . . . syn412K (AAg),
. . . . . . . . syn418F (TTt),
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn538F (TTt))

. . . . UkraineLuhansk5192_xF_2011_03_07 (
. . . . . . . . GISAID NA EPI346640
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . 83G,
. . . . . . . . syn206L (cTA),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . CameroonLEID03111573_xM_2011_03_01 (
. . . . . . . . GISAID HA EPI346687
. . . . . . . . 14 Polymorphisms (9 Amino and 5 Silent)
. . . . . . . . 1T,
. . . . . . . . syn157K (AAg),
. . . . . . . . 158E mix wt,
. . . . . . . . syn173G (GGa),
. . . . . . . . 190G,
. . . . . . . . 205E mix wt,
. . . . . . . . syn238E (GAa),
. . . . . . . . 275A,
. . . . . . . . syn286K (AAa),
. . . . . . . . syn334G (GGa),
. . . . . . . . 377K,
. . . . . . . . 476D,
. . . . . . . . 477K,
. . . . . . . . 523A)

. . . . CameroonLEID03111573_xM_2011_03_01 (
. . . . . . . . GISAID NA EPI346688
. . . . . . . . 4 Polymorphisms (0 Amino and 4 Silent)
. . . . . . . . syn6K (AAa),
. . . . . . . . syn22L (cTA),
. . . . . . . . syn262K (AAa),
. . . . . . . . syn398E (GAa))

. . . . UkraineOdessa5197_24F_2011_03_01 (
. . . . . . . . GISAID HA EPI346641
. . . . . . . . 3 Polymorphisms (1 Amino and 2 Silent)
. . . . . . . . syn391T (ACc),
. . . . . . . . syn413K (AAg),
. . . . . . . . 415E mix wt)

. . . . UkraineOdessa5197_24F_2011_03_01 (
. . . . . . . . GISAID NA EPI346642
. . . . . . . . 2 Polymorphisms (0 Amino and 2 Silent)
. . . . . . . . syn330D (GAc),
. . . . . . . . syn407V (GTc))


. . . . FranceLorraine1176_50x_2011_02_23_TmX (
. . . . . . . . GISAID HA EPI346699
. . . . . . . . Clade2: 188T
. . . . . . . . 11 Polymorphisms (6 Amino and 5 Silent)
. . . . . . . . 100N,
. . . . . . . . 158E mix wt,
. . . . . . . . 188T,
. . . . . . . . 227G,
. . . . . . . . syn245F (TTt),
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn461K (AAa),
. . . . . . . . syn470F (TTc),
. . . . . . . . syn537S (AGc))

. . . . FranceLorraine1176_50x_2011_02_23_TmX (
. . . . . . . . GISAID NA EPI346700
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 275Y,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . LithuaniaKlaipeda1067_xF_2011_02_22 (
. . . . . . . . GISAID HA EPI346673
. . . . . . . . Clade3: 186P
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . 137T,
. . . . . . . . 186P,
. . . . . . . . syn279N (AAc),
. . . . . . . . syn288A (GCc),
. . . . . . . . syn352Y (TAt),
. . . . . . . . 377G,
. . . . . . . . syn408E (GAa),
. . . . . . . . syn474C (TGt),
. . . . . . . . syn475D (GAc),
. . . . . . . . 512M,
. . . . . . . . 530I)

. . . . LithuaniaKlaipeda1067_xF_2011_02_22 (
. . . . . . . . GISAID NA EPI346674
. . . . . . . . 14 Polymorphisms (3 Amino and 11 Silent)
. . . . . . . . syn20A (GCc),
. . . . . . . . syn66Y (TAc),
. . . . . . . . syn124C (TGt),
. . . . . . . . syn130R (AGg),
. . . . . . . . syn157T (ACt),
. . . . . . . . syn175E (GAa),
. . . . . . . . 232V,
. . . . . . . . syn302P (CCa),
. . . . . . . . syn382G (GGa),
. . . . . . . . 389V,
. . . . . . . . 394I,
. . . . . . . . syn425E (GAg),
. . . . . . . . syn428R (AGg),
. . . . . . . . syn430R (CGg))

. . . . LithuaniaTelsiai1038_xM_2011_02_19 (
. . . . . . . . GISAID HA EPI346671
. . . . . . . . Clade2: 188T
. . . . . . . . 9 Polymorphisms (4 Amino and 5 Silent)
. . . . . . . . syn#6L (CTa),
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . syn245F (TTt),
. . . . . . . . syn321L (cTG),
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))

. . . . LithuaniaTelsiai1038_xM_2011_02_19 (
. . . . . . . . GISAID NA EPI346672
. . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . syn436I (ATa))

. . . . LithuaniaTelsiai1037_xM_2011_02_19 (
. . . . . . . . GISAID HA EPI346669
. . . . . . . . Clade2: 188T
. . . . . . . . 9 Polymorphisms (4 Amino and 5 Silent)
. . . . . . . . syn#6L (CTa),
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . syn245F (TTt),
. . . . . . . . syn321L (cTG),
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))

. . . . LithuaniaTelsiai1037_xM_2011_02_19 (
. . . . . . . . GISAID NA EPI346670
. . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . syn436I (ATa))

. . . . LithuaniaKaunas146s_xM_2011_02_17 (
. . . . . . . . GISAID HA EPI346675
. . . . . . . . Clade2: 188T
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . 152M,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N)

. . . . LithuaniaKaunas146s_xM_2011_02_17 (
. . . . . . . . GISAID NA EPI346676
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . syn162P (CCc),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . 453M)

. . . . LithuaniaKaunas988_xM_2011_02_15 (
. . . . . . . . GISAID HA EPI346667
. . . . . . . . Clade2: 188T
. . . . . . . . . . . . crossed with Clade4:128D
. . . . . . . . 9 Polymorphisms (6 Amino and 3 Silent)
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa) [Upsilon?],
. . . . . . . . 100N,
. . . . . . . . 128D,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))

. . . . LithuaniaKaunas988_xM_2011_02_15 (
. . . . . . . . GISAID NA EPI346668
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . FranceParis940_16x_2011_02_11 (
. . . . . . . . GISAID HA EPI346722
. . . . . . . . Clade2: 188T
. . . . . . . . 15 Polymorphisms (8 Amino and 7 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 76T,
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . 205E mix wt,
. . . . . . . . 277N,
. . . . . . . . syn338G (GGc),
. . . . . . . . syn358N (AAc),
. . . . . . . . 377K,
. . . . . . . . syn418F (TTt),
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn538F (TTt))

. . . . FranceParis940_16x_2011_02_11 (
. . . . . . . . GISAID NA EPI346723
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . FranceCentre869_60x_2011_02_08 (
. . . . . . . . GISAID HA EPI346681
. . . . . . . . Clade2: 188T
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . syn31H (CAt),
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 205E,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N)

. . . . FranceCentre869_60x_2011_02_08 (
. . . . . . . . GISAID NA EPI346682
. . . . . . . . 10 Polymorphisms (3 Amino and 7 Silent)
. . . . . . . . syn162P (CCc),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn316Y (TAt),
. . . . . . . . 344K,
. . . . . . . . syn365I (ATc),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn390K (AAa),
. . . . . . . . syn416D (GAc))

. . . . FranceHauteNormandie774_3x_2011_02_01 (
. . . . . . . . GISAID HA EPI346679
. . . . . . . . Clade5: 208K_219V
. . . . . . . . 14 Polymorphisms (7 Amino and 7 Silent)
. . . . . . . . syn41N (AAt),
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . 133E,
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . syn319T (ACg),
. . . . . . . . 352F,
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))

. . . . FranceHauteNormandie774_3x_2011_02_01 (
. . . . . . . . GISAID NA EPI346680
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . syn60T (ACc),
. . . . . . . . 81A,
. . . . . . . . syn138A (GCt),
. . . . . . . . 151N mix wt,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . Hungary13_xM_2011_01_31 (
. . . . . . . . GISAID HA EPI346711
. . . . . . . . Clade2: 188T
. . . . . . . . 9 Polymorphisms (6 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . 157E,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 226R,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N)

. . . . Hungary13_xM_2011_01_31 (
. . . . . . . . GISAID NA EPI346712
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . syn162P (CCc),
. . . . . . . . syn191L (tTA),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))


. . . . Hungary7_xM_2011_01_31 (
. . . . . . . . GISAID HA EPI346709
. . . . . . . . Clade2: 188T
. . . . . . . . 11 Polymorphisms (8 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . 157E mix wt,
. . . . . . . . 158E mix wt,
. . . . . . . . 159D mix wt,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 226R,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N)

. . . . Hungary7_xM_2011_01_31 (
. . . . . . . . GISAID NA EPI346710
. . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
. . . . . . . . syn162P (CCc),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . TurkeyMalatyaTR_29_28M_2011_01_28 (
. . . . . . . . GISAID HA EPI346659
. . . . . . . . Clade3: 186P
. . . . . . . . 11 Polymorphisms (8 Amino and 3 Silent)
. . . . . . . . syn16T (ACg),
. . . . . . . . 137T,
. . . . . . . . 167F,
. . . . . . . . 186P,
. . . . . . . . 263K,
. . . . . . . . 377G,
. . . . . . . . syn408E (GAa),
. . . . . . . . 413R mix wt,
. . . . . . . . syn474C (TGt),
. . . . . . . . 512M,
. . . . . . . . 530I)

. . . . TurkeyMalatyaTR_29_28M_2011_01_28 (
. . . . . . . . GISAID NA EPI346660
. . . . . . . . 13 Polymorphisms (4 Amino and 9 Silent)
. . . . . . . . syn20A (GCc),
. . . . . . . . syn66Y (TAc),
. . . . . . . . syn124C (TGt),
. . . . . . . . syn130R (AGg),
. . . . . . . . syn157T (ACt),
. . . . . . . . syn175E (GAa),
. . . . . . . . 232V,
. . . . . . . . 267I,
. . . . . . . . syn382G (GGa),
. . . . . . . . 389V,
. . . . . . . . 394I,
. . . . . . . . syn425E (GAg),
. . . . . . . . syn430R (CGg))

. . . . CameroonLEID01111467_28F_2011_01_27 (
. . . . . . . . GISAID HA EPI346705
. . . . . . . . Clade1: 189T
. . . . . . . . 11 Polymorphisms (7 Amino and 4 Silent)
. . . . . . . . 1T,
. . . . . . . . 189T,
. . . . . . . . syn238E (GAa),
. . . . . . . . 275A,
. . . . . . . . syn286K (AAa),
. . . . . . . . syn340I (ATc),
. . . . . . . . 377K,
. . . . . . . . syn403L (tTG),
. . . . . . . . 476D,
. . . . . . . . 477K,
. . . . . . . . 523A)

. . . . CameroonLEID01111467_28F_2011_01_27 (
. . . . . . . . GISAID NA EPI346706
. . . . . . . . 4 Polymorphisms (0 Amino and 4 Silent)
. . . . . . . . syn22L (cTA),
. . . . . . . . syn262K (AAa),
. . . . . . . . syn271A (GCt),
. . . . . . . . syn398E (GAa))

. . . . Kazakhstan2081_xF_2011_01_23 (
. . . . . . . . GISAID HA EPI346713
. . . . . . . . Clade3: 186P
. . . . . . . . 10 Polymorphisms (4 Amino and 6 Silent)
. . . . . . . . 137T,
. . . . . . . . 186P,
. . . . . . . . syn297N (AAc),
. . . . . . . . syn316R (AGg),
. . . . . . . . syn326S (TCc),
. . . . . . . . syn383N (AAc),
. . . . . . . . syn388K (AAa),
. . . . . . . . 433K,
. . . . . . . . 444K,
. . . . . . . . syn474C (TGt))

. . . . Kazakhstan2081_xF_2011_01_23 (
. . . . . . . . GISAID NA EPI346714
. . . . . . . . 7 Polymorphisms (1 Amino and 6 Silent)
. . . . . . . . syn6K (AAa),
. . . . . . . . syn139L (cTG),
. . . . . . . . syn202A (GCt),
. . . . . . . . syn274Y (TAc),
. . . . . . . . syn275H (CAt),
. . . . . . . . syn372E (GAa),
. . . . . . . . 394I)

. . . . CameroonLEID01111450_3F_2011_01_19 (
. . . . . . . . GISAID HA EPI346649
. . . . . . . . Clade1: 189T
. . . . . . . . 12 Polymorphisms (9 Amino and 3 Silent)
. . . . . . . . 1T,
. . . . . . . . 159S,
. . . . . . . . 189T,
. . . . . . . . 205E,
. . . . . . . . syn238E (GAa),
. . . . . . . . 275A,
. . . . . . . . syn286K (AAa),
. . . . . . . . 377K,
. . . . . . . . syn403L (tTG),
. . . . . . . . 476D,
. . . . . . . . 477K,
. . . . . . . . 523A)

. . . . CameroonLEID01111450_3F_2011_01_19 (
. . . . . . . . GISAID NA EPI346650
. . . . . . . . 4 Polymorphisms (1 Amino and 3 Silent)
. . . . . . . . syn22L (cTA),
. . . . . . . . 59R,
. . . . . . . . syn262K (AAa),
. . . . . . . . syn398E (GAa))

. . . . Iceland9_xF_2011_01_19 (
. . . . . . . . GISAID HA EPI346695
. . . . . . . . Clade2: 188T
. . . . . . . . 15 Polymorphisms (10 Amino and 5 Silent)
. . . . . . . . 100N,
. . . . . . . . 159D,
. . . . . . . . syn179L (tTA),
. . . . . . . . 188T,
. . . . . . . . 225N,
. . . . . . . . syn245F (TTt),
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 437I (Atc) mix wt,
. . . . . . . . 437I (Att) mix wt,
. . . . . . . . 437N (Aac) mix wt,
. . . . . . . . 437N (Aat) mix wt,
. . . . . . . . syn437T (Acc) mix wt,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))

. . . . Iceland9_xF_2011_01_19 (
. . . . . . . . GISAID NA EPI346696
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . TurkeyTokatTR_26_26M_2011_01_19 (
. . . . . . . . GISAID HA EPI346657
. . . . . . . . Clade5: 208K_219V
. . . . . . . . . . . . crossing Clade4: 128D
. . . . . . . . 14 Polymorphisms (8 Amino and 6 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . 128D,
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 210I mix wt,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . 431Q mix wt,
. . . . . . . . syn446K (AAa))

. . . . TurkeyTokatTR_26_26M_2011_01_19 (
. . . . . . . . GISAID NA EPI346658
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . syn60T (ACc),
. . . . . . . . 81A,
. . . . . . . . syn138A (GCt),
. . . . . . . . 211T mix wt,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . Iceland7_xM_2011_01_16 (
. . . . . . . . GISAID HA EPI346661
. . . . . . . . Clade2: 188T
. . . . . . . . 10 Polymorphisms (7 Amino and 3 Silent)
. . . . . . . . #7I,
. . . . . . . . 100N,
. . . . . . . . 157N mix wt,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn448L (TTg),
. . . . . . . . 449C mix wt,
. . . . . . . . 454N)

. . . . Iceland7_xM_2011_01_16 (
. . . . . . . . GISAID NA EPI346662
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . 117M,
. . . . . . . . syn162P (CCc),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . Iceland3_xM_2011_01_10 (
. . . . . . . . GISAID HA EPI346677
. . . . . . . . Clade2: 188T
. . . . . . . . 12 Polymorphisms (6 Amino and 6 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . syn122K (AAa),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn379T (ACc),
. . . . . . . . 440H,
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn538F (TTt))

. . . . Iceland3_xM_2011_01_10 (
. . . . . . . . GISAID NA EPI346678
. . . . . . . . 10 Polymorphisms (6 Amino and 4 Silent)
. . . . . . . . syn38I (ATc),
. . . . . . . . 44S,
. . . . . . . . 151E mix wt,
. . . . . . . . 151K mix wt,
. . . . . . . . 151N mix wt,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn274Y (TAc),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . TurkeyAnkaraTR_23_20M_2010_12_30 (
. . . . . . . . GISAID HA EPI346693
. . . . . . . . Clade5: 208K_219V
. . . . . . . . . . . . crossing Clade3: 186P
. . . . . . . . 15 Polymorphisms (9 Amino and 6 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . 159D mix wt,
. . . . . . . . syn170N (AAc),
. . . . . . . . 186P mix wt,
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn346G (GGa),
. . . . . . . . 377K,
. . . . . . . . 426V,
. . . . . . . . syn446K (AAa),
. . . . . . . . syn507K (AAa),
. . . . . . . . 530I)

. . . . TurkeyAnkaraTR_23_20M_2010_12_30 (
. . . . . . . . GISAID NA EPI346694
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . syn238C (TGt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . UKEngland687_2010_12_15 (
. . . . . . . . GISAID HA EPI346665
. . . . . . . . Clade2: 188T
. . . . . . . . 11 Polymorphisms (7 Amino and 4 Silent)
. . . . . . . . syn#7V (GTc),
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa),
. . . . . . . . 100N,
. . . . . . . . 158E mix wt,
. . . . . . . . 179I,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))

. . . . UKEngland687_2010_12_15 (
. . . . . . . . GISAID NA EPI346666
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . syn161C (TGc),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn398E (GAa),
. . . . . . . . syn416D (GAc))


This analysis catalysed with ingenuity from 2 lead Professors of Group10 at Ion₂₀₃.  We never cease to find inspiration in your halls of instruction.

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Greece Deposits pH1N1 Clade5 from 2011 Hospitalisation with Novel Diversity

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 Update
2011-11-05

On 2011-10-31, the Institut Pasteur Hellenique deposited one human pH1N1 HA fragment sequence at GISAID of 216 amino acids (aa35 to aa220), documenting roughly 38% of a full pH1N1 Hemagglutinin segment.  GreeceAthens7033_75M_2011_02_22_s was sampled from a 75 year old male, hospital inpatient.  This hypermorphic fragment patterns onto Clade5: 208K_219V, a highly zoonotic, recently emergent series with a sequence count that has quickly accumulated to triple digits.

Two dispersed polymorphisms, each novel to pH1N1.Clade5, appear on this Greek sequence.  HA 77R, a novel Clade5 revision, is rare to the human pandemic and is emergent on Clade2 (3 instances).  Those 3 Clade2, HA 77R-bearing HA segment sequences are hypermorphic (accounting for 48 total HA changes); however, no HA cross-over onto this Greek sequence occurs from the full superset of polymorphisms with HA 77R.  HA 169T, also novel to Clade5, is rare to the human pandemic and is found once on Clade2, the numerically dominant series for human pH1N1.

Avian H13 serotypes share significant homology with pH1N1.Clade5 and this Greek sequence.  Given the serology background of the more recently discovered Hemagglutinin forms above H12 (~30 years for H13 to ~6 years for H16), question arise concerning cross-serotype compatibility.  Returning to the archives after these recent discoveries, investigators repeatedly found that H16 samples from the past had been mis-typed on first inspection to various Hemagglutinin forms (H1, H7, H13) due to cross-reactive serology on various inhibition panels.  Serotypes known to infect humans, including H1 and H7, featured in those earlier mistaken categorisations. 

Precise discernment of the exact relationship between the current human pandemic H1N1 and the more recently discovered Hemagglutinin forms (H13 to H16) merits evaluation due to the significant H13 homology with the heavily zoonotic and rapidly emergent pH1N1.Clade5 and the High CFR pH1N1.Clade1.Upsilon.

Sequence

. . . . GreeceAthens7033_75M_2011_02_22_s (
. . . . . . . . Clade5: 208K_219V
. . . . . . . . GISAID HA EPI340964
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . HA Truncated before aa35,
. . . . . . . . syn47L (CTg) [H1N1 Avian],
. . . . . . . . 77R (AGa) [Rare to Human pH1N1 (11 Total / 5 Asia)],
. . . . . . . . . . . . . . . [Novel to pH1N1.Clade5],
. . . . . . . . . . . . . . . [Emergent pH1N1.Clade2 (3)],
. . . . . . . . . . . . . . . [H9N2 Avian and Human wt
. . . . . . . . . . . . . . . . . . . . with pH1N1υ polymorphisms],
. . . . . . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . . . . [WSN_1933, WSZ_1933],
. . . . . . . . 100N [H5N1 Egypt Avian 2009-2010
. . . . . . . . . . . . . . . . . with syn40H, syn55L, 192I, 196K],
. . . . . . . . . . . . [H5N1 Egypt Avian 2008 with syn40H, syn55L],
. . . . . . . . . . . . [H5N2 Italy Avian 2005-2007],
. . . . . . . . . . . . [H7N3, H7N7, H9N2],
. . . . . . . . . . . . [H13N2 Mammal],
. . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . syn102E (GAa) [H5N1 wt],
. . . . . . . . . . . . . . . . . . . [H9N2 Early Human wt, Human 2008],
. . . . . . . . . . . . . . . . . . . [H9N2 Avian wt],
. . . . . . . . . . . . . . . . . . . [H10N7 Avian 2008
. . . . . . . . . . . . . . . . . . . . . . with 87N, 100N, syn102E,
. . . . . . . . . . . . . . . . . . . . . . . . 156E, 157E, 163T, 165N,
. . . . . . . . . . . . . . . . . . . . . . . . syn177L, 188T, syn221P, syn207S, syn213F,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, 230I, 233H, 237I, syn239P,
. . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn356H,
. . . . . . . . . . . . . . . . . . . . . . . . syn390N, syn391T],
. . . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 169T [Rare to Human pH1N1 (6 Total / 3 Asia)],
. . . . . . . . . . . [Novel to pH1N1.Clade5],
. . . . . . . . . . . [Singular to pH1N1.Clade2],
. . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . . . . [H1N1 swine],
. . . . . . . . syn170N (AAc) [H5N1 Egypt Human 2009],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . . . [H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . . . with 225G & 252L],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K (AaA) [pH1N1 Canine 2009],
. . . . . . . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . . . . . . . . . [H3N2 Avian 2006, 2009],
. . . . . . . . 219V (gTA) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . [H13N2, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . syn221P (CCt) [H3N2 Avian
. . . . . . . . . . . . . . . . . . . . . with 157S, 159S, syn287G],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human and Avian (tCt)],
. . . . . . . . . . . . . . . . . . [H5N1 Nigeria Avian (tCt)],
. . . . . . . . . . . . . . . . . . [H10N7 Avian 2008
. . . . . . . . . . . . . . . . . . . . . . . with #1V, 87N, syn94Y, 100N, syn102E,
. . . . . . . . . . . . . . . . . . . . . . . . . . . 156E, 157E, 163T, 165N,
. . . . . . . . . . . . . . . . . . . . . . . . . . . syn177L, 188T, syn221P, syn207S, syn213F,
. . . . . . . . . . . . . . . . . . . . . . . . . . . 225G, 230I, 233H, 237I, syn239P,
. . . . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn356H,
. . . . . . . . . . . . . . . . . . . . . . . . . . . syn390N, syn391T],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal],
. . . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . HA Truncated after aa250)

Supporting Sequences

HA 169T

. . . . Montana03_2011_02_02 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI310031
. . . . . . . . 8 Polymorphisms (6 Amino and 2 Silent)
. . . . . . . . 100N,
. . . . . . . . 169T,
. . . . . . . . 188T,
. . . . . . . . 213S,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))

. . . . Lebanon09L_29_2009_11_05 (
. . . . . . . . GISAID HA EPI320624
. . . . . . . . 4 Polymorphisms (4 Amino and 0 Silent)
. . . . . . . . #1T,
. . . . . . . . 169T,
. . . . . . . . 225E,
. . . . . . . . 300S,
. . . . . . . . HA Truncated after aa355)

. . . . ShanxiChengquSWL547_2009_10_19 (
. . . . . . . . GISAID HA EPI256314
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . 57N,
. . . . . . . . 131P,
. . . . . . . . 169T,
. . . . . . . . syn238E (GAa))

. . . . TianjinTangguSWL1110_2009_10_13 (
. . . . . . . . GISAID HA EPI256126
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . 169T,
. . . . . . . . 206S,
. . . . . . . . 447K,
. . . . . . . . syn455Q (CAa))

. . . . BeijingHuairouSWL1805_2009_10_01 (
. . . . . . . . GISAID HA EPI256274
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . 169T,
. . . . . . . . 206S,
. . . . . . . . 447K,
. . . . . . . . syn455Q (CAa))

. . . . Russia01_MA_2009 (
. . . . . . . . GISAID HA EPI297205
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . 169T,
. . . . . . . . 208K,
. . . . . . . . syn359E (GAa))

HA 77R on Clade2

. . . . OzBrisbane500_2011_06_22 (
. . . . . . . . GISAID HA EPI333109
. . . . . . . . 18 Polymorphisms (8 Amino and 10 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn33V (GTc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 77R,
. . . . . . . . syn99I (ATt),
. . . . . . . . syn115E (GAg),
. . . . . . . . 146G,
. . . . . . . . 171G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn338G (GGc),
. . . . . . . . syn346G (GGa),
. . . . . . . . 377K,
. . . . . . . . syn413K (AAg),
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn508L (tTG),
. . . . . . . . 523A,
. . . . . . . . HA Truncated after aa552)

. . . . OzNewcastle1_2011_04_11 (
. . . . . . . . GISAID HA EPI331558
. . . . . . . . 21 Polymorphisms (9 Amino and 12 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn33V (GTc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 77R,
. . . . . . . . syn99I (ATt),
. . . . . . . . syn115E (GAg),
. . . . . . . . 146G,
. . . . . . . . 157Q mix wt,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn338G (GGc),
. . . . . . . . syn346G (GGa),
. . . . . . . . 377K,
. . . . . . . . syn413K (AAg),
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn508L (tTG),
. . . . . . . . 523A,
. . . . . . . . syn538F (TTt),
. . . . . . . . syn549R (AGg),
. . . . . . . . 550S,
. . . . . . . . HA Truncated after aa550)

. . . . JapanHiroshimaC2_2011_01_05 (
. . . . . . . . GISAID HA EPI305466
. . . . . . . . 9 Polymorphisms (6 Amino and 3 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 71D,
. . . . . . . . 77R,
. . . . . . . . 102G mix wt,
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa348)

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Mexico Evaluates Upper Respiratory Swabs from Fatal and Severe Cases with 225A, 225G, 225N & 225V

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 Update
2011-11-03

On 2011-10-27, the Instituto Nacional de Enfermedades Respiratorias from the Centro de Investigacion en Enfermedades Infecciosas of Mexico deposited a group of human pH1N1 sequences at GenBank and GISAID.  The deposit is composed of HA segments, 14 sequence fragments of 232 amino acids (aa38 to aa269), each documenting roughly 41% of a full pH1N1 Hemagglutinin segment.  Various homology to Clade1.Upsilon exists on 5 of the sequences.

This Mexican genetic data supports an investigation entitled, H1N1pdm HA D222 variants associated with severity and mortality in patients during a second wave in Mexico and their pathogenicity in mouse model.  Mexico City, Mexico is the geography indicated on the sequence names.  Each sequence is annotated with gender and isolation source (nasopharyngeal swab), while 12 of the 14 also indicate the subject age.  Subject ages range from 23 to 54 years old, all outside the general severity range for seasonal influenza (under 2 years old or over 60 years old).  The sample dates span 2009-10-01 to 2010-04-05 with no case-level specification of treatment protocol, clinical progression or clinical outcome.

The severity and fatality correlation in cases with polymorphisms at amino acid position 222 (aa225 in H3 numbering) was established very early in the pandemic.  The issue of sample location has been repeatedly posed, with ongoing discussion that samples taken from the lower respiratory tract are more probable to produce valid evidence of aa225 revisions.  This INER deposit, relying entirely on upper respiratory swabs, documents cases where aa225 revisions are found in the upper airway.  The individual details of clinical progression and outcome (severe v. fatal) will establish measurable correlation to the upper respiratory sample location.

Four of the samples show multi-nucleotide ambiguity at amino acid position 225 (contiguous mixed traces, residues 715 and 716) producing a codon of rrT.  That sequencing outcome of rrT demonstrates the presence of wild type D225 with both 225G and 225N, hypermorphism at a single amino acid position.  Overall, ten of the fourteen sequences demonstrate a mixed peak (ambiguity) at one or more nucleotides that build aa225.  MexicoCityINER3_NP_47M_2009_10_15 [EPI341034] illustrates the highly variant nature of the pH1N1 reservoir Receptor Binding Site aa225 with two rare values, 225A and 225V, in a mixture without wild type (D225) and with no additional polymorphisms.

Sequences

. . . . MexicoCityINER14_NP_xF_2010_04_05 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341023
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn71E (GAg) mix wt [H6N1],
. . . . . . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . syn100D (GAc) [H1N1 Avian Farm],
. . . . . . . . 165N,
. . . . . . . . 181S,
. . . . . . . . 189T,
. . . . . . . . syn198A (GCg) mix wt,
. . . . . . . . syn213F (TTt),
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER13_NP_48F_2010_03_25 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341024
. . . . . . . . 6 Polymorphisms (5 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER12_NP_37M_2010_03_23 (
. . . . . . . . GISAID HA EPI341025
. . . . . . . . 2 Polymorphisms (2 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 122R,
. . . . . . . . 225N,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER11_NP_34F_2010_02_09 (
. . . . . . . . GISAID HA EPI341026
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn214K (AAa) [H9N2],
. . . . . . . . . . . . . . . . . . [H13N2 Avian],
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER10_NP_39M_2010_02_09 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341027
. . . . . . . . 4 Polymorphisms (2 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn58C (TGc) [H2N3, H3N8, H4, H6],
. . . . . . . . . . . . . . . . . [H7N3, H7N7],
. . . . . . . . . . . . . . . . . [H9N2, H11],
. . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 225G,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER8_NP_23F_2009_11_23 (
. . . . . . . . GISAID HA EPI341029
. . . . . . . . 3 Polymorphisms (1 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn106E (GAa) [H1N1 Avian],
. . . . . . . . syn189A (GCc),
. . . . . . . . 225G,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER9_NP_49M_2010_01_18 (
. . . . . . . . GISAID HA EPI341028
. . . . . . . . 1 Polymorphisms (1 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER7_NP_54F_2009_11_09 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341030
. . . . . . . . 3 Polymorphisms (3 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 157T,
. . . . . . . . 165N,
. . . . . . . . 225G,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER6_NP_22F_2009_11_06 (
. . . . . . . . GISAID HA EPI341031
. . . . . . . . 3 Polymorphisms (1 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn106E (GAa) [H1N1 Avian],
. . . . . . . . syn189A (GCc),
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER5_NP_52F_2009_10_27 (
. . . . . . . . GISAID HA EPI341032
. . . . . . . . 1 Polymorphisms (1 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER4_NP_xM_2009_10_16 (
. . . . . . . . GISAID HA EPI341033
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn145K (AAg),
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER3_NP_47M_2009_10_15 (
. . . . . . . . GISAID HA EPI341034
. . . . . . . . 2 Polymorphisms (2 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 225A mix,
. . . . . . . . 225V mix,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER2_NP_44F_2009_10_12 (
. . . . . . . . GISAID HA EPI341035
. . . . . . . . 3 Polymorphisms (3 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER1_NP_40M_2009_10_01 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341036
. . . . . . . . 4 Polymorphisms (4 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 165N,
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . HA Truncated after aa269)

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Morocco Reports Hypermorphism on pH1N1 HA and NA Fragments

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 Update
2011-11-03

On 2011-10-25, the Institute Pasteur of Morocco deposited a group of human pH1N1 sequences at GenBank and GISAID.  HA segments include 14 fragments.  The NA segment is represented with 15 fragments, 7 that are related to a deposited HA fragment.  All sequences are marked geographically as Casablanca.  The sample dates span 2010-12-20 to 2011-04-01 with no specification of treatment protocol, clinical progression or clinical outcome.

Hypermorphic behaviour is found on 71% of the sequences that have both HA and NA segments, notwithstanding the fact that both segments are fragments across this deposit.  These 5 hypermorphic representatives are on two separate lineages. Additionally, the NA fragment of  MoroccoCasablanca69_11F_2011_01_26  [EPI340865] demonstrates significant, rare zoonotic homology to Avian H1N1, H5N1 and Avian H9N2.

Multi-clade hypermorphism in a single geography and within a contemporaneous time span merits careful evaluation.

Zoonoses of Polymorphisms

The mammal and avian database of Influenza A H13 covering all Neuraminidase forms comprises only 93 sequences, yet shares homology to pH1N1 human polymorphisms on Clade1.Upsilon as well as rare and novel pH1N1 human polymorphisms on Clade2, Clade4 and Clade5 sequences in this Moroccan deposit.  Several of these shared polymorphisms, e.g. markers for Clade5 (HA 219V and HA 252L), are previously uncharacterised as to potential Ultimate Origin.  The identification of multi-clade hypermorphism in this geography with wide homology to a single candidate animal reservoir (A/H13) solidifies the clear requirement for higher levels of avian surveillance.

Cladistics

10 - Clade2: 188T
01 - Clade4: 128D [EPI340861]
03 - Clade5: 208K_219V [EPI340881], [EPI340860], [EPI340876]

HA   84 Polymorphisms Averaging ~6.0 per Segment Fragment
NA 118 Polymorphisms Averaging ~7.9 per Segment Fragment

HA and NA 202 Total Polymorphisms Averaging ~13.9 per Sequence (Fragments)

Diversity

HA Superset – 36 Distinct Values
NA Superset - 47 Distinct Values

Two Receptor Binding Site items of interest are syn221P and 224K.  No indication is found of revisions at aa225, aa226 or aa230.  The Clade5 sequence bearing HA syn221P is contemporary in timing and homology to a small group of European Clade5 sequences.  A hypermorphic, Clade2 Moroccan sequence bears HA 224K, a polymorphism previously found in pH1N1 swine Clade5, suggesting a potential cross-clade transfer or compatibility.  The HA 224K may signal tissue tropism issues, having been documented on a lethal, neurotropic experimental strain (WSN_1933).

• [EPI340860] MoroccoCasablanca91_15mM_2011_02_02 – HA syn221P
• [EPI340866] MoroccoCasablanca69_11F_2011_01_26    – HA 224K

Hypermorphic Behaviour

04 HA Fragments >= 7 polymorphisms (29%)
13 NA Segments  >= 7 polymorphisms (87%)

Combined Polymorphic Count >= 15
5 of 7 Sequences with HA and NA Fragments (71%)
Total (HA / NA)

• 16 (HA 09 / NA 07): [EPI340881] MoroccoCasablanca117_10m_2011_02_15
• 16 (HA 07 / NA 09): [EPI340860] MoroccoCasablanca91_15mM_2011_02_02
• 16 (HA 05 / NA 11): [EPI340866] MoroccoCasablanca69_11F_2011_01_26
• 16 (HA 09 / NA 07): [EPI340876] MoroccoCasablanca23_3F_2011_01_13
• 15 (HA 09 / NA 07): [EPI340868] MoroccoCasablanca63_47F_2011_01_20

Sequences

. . . . MoroccoCasablanca124_5M_2011_04_01 (
. . . . . . . . GISAID NA EPI340879
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . NA Truncated before aa36,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca211_15M_2010_12_20 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340885
. . . . . . . . 4 Polymorphisms (2 Amino and 2 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa354)

. . . . MoroccoCasablanca117_10m_2011_02_15 (
. . . . . . . . Clade5: 208K_219V crossing with
. . . . . . . . . . . Clade2: 188T Defining Marker syn338G
. . . . . . . . GISAID HA EPI340881
. . . . . . . . 9 Polymorphisms (4 Amino and 5 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian],
. . . . . . . . syn82I (ATc) [H5N2 Avian],
. . . . . . . . syn93C (TGc) [H5N1 Avian Domestic & Wild],
. . . . . . . . . . . . . . . . . [H9N2 Avian Emergent 2009],
. . . . . . . . . . . . . . . . . [H13N2 Mammal],
. . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . 100N [H5N1 Egypt Avian 2009-2010
. . . . . . . . . . . . . . . with syn40H, syn55L, 192I, 196K],
. . . . . . . . . . . . [H5N1 Egypt Avian 2008 with syn40H, syn55L],
. . . . . . . . . . . . [H5N2 Italy Avian 2005-2007],
. . . . . . . . . . . . [H7N3, H7N7, H9N2],
. . . . . . . . . . . . [H13N2 Mammal],
. . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 141Q (CAa) [H13 Avian (gAa, gga)],
. . . . . . . . syn170N (AAc) [H5N1 Egypt Human 2009],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . . . [H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . . . with 225G & 252L],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K (AaA) [pH1N1 Canine 2009],
. . . . . . . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . . . . . . . . . [H3N2 Avian 2006, 2009],
. . . . . . . . 219V (gTA) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . [H13N2, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . syn338G (GGc) [Clade2, Rare to Clade5],
. . . . . . . . HA Truncated after aa342)

. . . . MoroccoCasablanca117_10m_2011_02_15 (
. . . . . . . . GISAID NA EPI340880
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . NA Truncated before aa33,
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H1N1 Avian (Cat)],
. . . . . . . . . . . . . . . . . .[H9N2 Avian (Ctt)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 299A,
. . . . . . . . 454V [Rare to pH1N1 (1)],
. . . . . . . . NA Truncated after aa454)

. . . . MoroccoCasablanca110_3F_2011_02_09 (
. . . . . . . . GISAID NA EPI340882
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa38,
. . . . . . . . 38V [H9N2 Avian],
. . . . . . . . syn60T (ACc) [H1N1 Avian Farm],
. . . . . . . . 81A [H1N1 Avian],
. . . . . . . . syn138A (GCt) [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . 192N [H9N2 Avian (cac)],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca107_xF_2011_02_09 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340883
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#4,
. . . . . . . . 100N,
. . . . . . . . 173R,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa341)

. . . . MoroccoCasablanca103_5M_2011_02_07 (
. . . . . . . . GISAID HA EPI340884
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#7,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 324D [Novel to pH1N1],
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa350)

. . . . MoroccoCasablanca92_52F_2011_02_02 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340858
. . . . . . . . 8 Polymorphisms (6 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#3,
. . . . . . . . 22E [Novel to pH1N1],
. . . . . . . . 34T [Novel to pH1N1 2011],
. . . . . . . . 47Q [Novel to pH1N1],
. . . . . . . . 60V [H1N1 Avian],
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa341)

. . . . MoroccoCasablanca91_15mM_2011_02_02 (
. . . . . . . . Clade5: 208K_219V
. . . . . . . . GISAID HA EPI340860
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa82,
. . . . . . . . 100F [Novel to pH1N1],
. . . . . . . . syn102E (GAa) [H5N1 wt],
. . . . . . . . . . . . . . . . . [H9N2 Early Human wt, Human 2008],
. . . . . . . . . . . . . . . . . [H9N2 Avian wt],
. . . . . . . . . . . . . . . . . [H10N7 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 87N, 100N, syn102E,
. . . . . . . . . . . . . . . . . . . . . . 156E, 157E, 163T, 165N,
. . . . . . . . . . . . . . . . . . . . . . syn177L, 188T, syn221P, syn207S, syn213F,
. . . . . . . . . . . . . . . . . . . . . . 225G, 230I, 233H, 237I, syn239P,
. . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn356H,
. . . . . . . . . . . . . . . . . . . . . . syn390N, syn391T],
. . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn170N (AAc) [H5N1 Egypt Human 2009],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . . . [H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . . . with 225G & 252L],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K (AaA) [pH1N1 Canine 2009],
. . . . . . . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . . . . . . . . . [H3N2 Avian 2006, 2009],
. . . . . . . . 219V (gTA) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . [H13N2, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . syn221P (CCt) [H3N2 Avian
. . . . . . . . . . . . . . . . . . . . . with 157S, 159S, syn287G],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human and Avian (tCt)],
. . . . . . . . . . . . . . . . . . [H5N1 Nigeria Avian (tCt)],
. . . . . . . . . . . . . . . . . . [H10N7 Avian 2008
. . . . . . . . . . . . . . . . . . . . . . . with #1V, 87N, syn94Y, 100N, syn102E,
. . . . . . . . . . . . . . . . . . . . . . . . . . . 156E, 157E, 163T, 165N,
. . . . . . . . . . . . . . . . . . . . . . . . . . . syn177L, 188T, syn221P, syn207S, syn213F,
. . . . . . . . . . . . . . . . . . . . . . . . . . . 225G, 230I, 233H, 237I, syn239P,
. . . . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn356H,
. . . . . . . . . . . . . . . . . . . . . . . . . . . syn390N, syn391T],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive Upsilon polymorphisms],
. . . . . . . . 252L (tTG) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . HA Truncated after aa352)

. . . . MoroccoCasablanca91_15mM_2011_02_02 (
. . . . . . . . GISAID NA EPI340859
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa36,
. . . . . . . . 69V [H1N1 Avian],
. . . . . . . . 81A [H1N1 Avian],
. . . . . . . . 106M,
. . . . . . . . syn138A (GCt) [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn395G (GGg),
. . . . . . . . NA Truncated after aa452)

. . . . MoroccoCasablanca76_13M_2011_01_26 (
. . . . . . . . Clade4: 128D
. . . . . . . . GISAID HA EPI340861
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa13,
. . . . . . . . 28P [Novel to pH1N1.Clade4],
. . . . . . . . . . . [pH1N1 with Avian Influence (3)],
. . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . with 188T, syn210S, 225G & 252L],
. . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . with 188T, syn210S, 225G & 252L],
. . . . . . . . syn60I (ATc) [H9N2 Human and Avian Emergent],
. . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6,
. . . . . . . . . . . . . . . . . . . H13N8, H13N9 Avian (tTc)
. . . . . . . . . . . . . . . . . . . . . . with 28P, 188T, syn210S],
. . . . . . . . . . . . . . . . [1918],
. . . . . . . . 128D,
. . . . . . . . syn210S (AGt) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . . . with 28P, 188T, 225G & 252L],
. . . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . . . with 28P, 188T, 225G & 252L],
. . . . . . . . 298V [H3N2 Avian, Canine, Feline & Mink],
. . . . . . . . . . . [H3N8],
. . . . . . . . . . . [H5 Avian, H6 Avian],
. . . . . . . . . . . [H9N2],
. . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . HA Truncated after aa341)

. . . . MoroccoCasablanca73_43F_2011_01_26 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340863
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa0,
. . . . . . . . 11L [Novel to pH1N1],
. . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . with 28P, 188T, syn210S, 225G & 252L],
. . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . with 28P, 188T, syn210S, 225G & 252L],
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 259T [Recently Novel to pH1N1υ],
. . . . . . . . . . . . [H9N2 Avian and Human (att)
. . . . . . . . . . . . . . . . with syn40H],
. . . . . . . . . . . . [Not Found in H1N1 Swine with 124N],
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa338)

. . . . MoroccoCasablanca73_43F_2011_01_26 (
. . . . . . . . GISAID NA EPI340862
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . NA Truncated before aa44,
. . . . . . . . syn126P (CCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn293R (AGa) [H1N1 Avian Farm],
. . . . . . . . . . . . . . . . . . . [H5N1 Avian],
. . . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca69_11F_2011_01_26 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340866
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#5,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 224K [swine pH1N1.Clade5]
. . . . . . . . . . . . [WSN_1933],
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa339)

. . . . MoroccoCasablanca69_11F_2011_01_26 (
. . . . . . . . GISAID NA EPI340865
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . NA Truncated before aa35,
. . . . . . . . 70N [H1N1 Avian],
. . . . . . . . syn137G (GGa) [H1N1 Avian],
. . . . . . . . syn215T (ACa) [H1N1 Avian],
. . . . . . . . 235D [H9N2 Avian],
. . . . . . . . syn240T (ACc) [H1N1 Avian],
. . . . . . . . 241I [H1N1 Avian],
. . . . . . . . 260R [H1N1 Avian],
. . . . . . . . 369K [H1N1 Avian],
. . . . . . . . syn377P (CCa) [H1N1 Avian],
. . . . . . . . syn386N (AAt) [H1N1 Environment],
. . . . . . . . syn416D (GAc) [H5N1 wt],
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca63_47F_2011_01_20 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340868
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa3,
. . . . . . . . syn90N (AAc) [Rare to pH1N1],
. . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa339)

. . . . MoroccoCasablanca63_47F_2011_01_20 (
. . . . . . . . GISAID NA EPI340867
. . . . . . . . 10 Polymorphisms (6 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa20,
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 262N,
. . . . . . . . 263V [H1N1 Avian],
. . . . . . . . . . . . [H5N1 wt],
. . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . 269I [H5N1 (tTa)],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . 420C,
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca60_43F_2011_01_20 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340869
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa#3,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn205G (GGa),
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa338)

. . . . MoroccoCasablanca54_23F_2011_01_20 (
. . . . . . . . GISAID NA EPI340870
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa17,
. . . . . . . . 54L,
. . . . . . . . 81A [H1N1 Avian],
. . . . . . . . syn138A (GCt) [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn395G (GGg),
. . . . . . . . NA Truncated after aa454)

. . . . MoroccoCasablanca52_25F_2011_01_20 (
. . . . . . . . GISAID NA EPI340871
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . NA Truncated before aa19,
. . . . . . . . 43R,
. . . . . . . . 44T,
. . . . . . . . 45L,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa452)

. . . . MoroccoCasablanca28_10M_2011_01_13 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340873
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#6,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 340M,
. . . . . . . . HA Truncated after aa340)

. . . . MoroccoCasablanca28_10M_2011_01_13 (
. . . . . . . . GISAID NA EPI340872
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . NA Truncated before aa21,
. . . . . . . . 54V [H1N1 Avian],
. . . . . . . . . . [H9N2 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . 454V [Rare to pH1N1 (1)],
. . . . . . . . NA Truncated after aa454)

. . . . MoroccoCasablanca26_24M_2011_01_13 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340874
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . syn136T (ACt),
. . . . . . . . 176I,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa353)

. . . . MoroccoCasablanca23_3F_2011_01_13 (
. . . . . . . . Clade5: 208K_219V
. . . . . . . . GISAID HA EPI340876
. . . . . . . . 9 Polymorphisms (4 Amino and 5 Silent)
. . . . . . . . HA Truncated before aa#7,
. . . . . . . . syn36L (tTA) [H5N1 Avian (tTg)],
. . . . . . . . syn47L (CTg) [H1N1 Avian],
. . . . . . . . 100N [H5N1 Egypt Avian 2009-2010
. . . . . . . . . . . . . . . . . with syn40H, syn55L, 192I, 196K],
. . . . . . . . . . . . [H5N1 Egypt Avian 2008 with syn40H, syn55L],
. . . . . . . . . . . . [H5N2 Italy Avian 2005-2007],
. . . . . . . . . . . . [H7N3, H7N7, H9N2],
. . . . . . . . . . . . [H13N2 Mammal],
. . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . syn102E (GAa) [H5N1 wt],
. . . . . . . . . . . . . . . . . . . [H9N2 Early Human wt, Human 2008],
. . . . . . . . . . . . . . . . . . . [H9N2 Avian wt],
. . . . . . . . . . . . . . . . . . . [H10N7 Avian 2008
. . . . . . . . . . . . . . . . . . . . . . with 87N, 100N, syn102E,
. . . . . . . . . . . . . . . . . . . . . . . . 156E, 157E, 163T, 165N,
. . . . . . . . . . . . . . . . . . . . . . . . syn177L, 188T, syn221P, syn207S, syn213F,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, 230I, 233H, 237I, syn239P,
. . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn356H,
. . . . . . . . . . . . . . . . . . . . . . . . syn390N, syn391T],
. . . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn170N (AAc) [H5N1 Egypt Human 2009],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . . . [H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . . . with 225G & 252L],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn184H (CAc) [Early pH1N1 Highly Zoonotic]
. . . . . . . . . . . . . . . . . . [swine pH1N1.Clade5],
. . . . . . . . . . . . . . . . . . [H2N3, H3N8],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Fatality 2010],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2009],
. . . . . . . . . . . . . . . . . . [H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal],
. . . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 208K (AaA) [pH1N1 Canine 2009],
. . . . . . . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . . . . . . . . . [H3N2 Avian 2006, 2009],
. . . . . . . . 219V (gTA) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . [H13N2, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . 252L (tTG) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . HA Truncated after aa335)

. . . . MoroccoCasablanca23_3F_2011_01_13 (
. . . . . . . . GISAID NA EPI340875
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa39,
. . . . . . . . syn87G (GGg) [H9N2 Avian (aag)],
. . . . . . . . syn138A (GCt) [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 242V [H9N2 Avian],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . NA Truncated after aa455)

. . . . MoroccoCasablanca17_12F_2011_01_07 (
. . . . . . . . GISAID NA EPI340877
. . . . . . . . 8 Polymorphisms (3 Amino and 5 Silent)
. . . . . . . . NA Truncated before aa35,
. . . . . . . . syn176S (TCg) [H1N1 Avian],
. . . . . . . . 213K,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn338V (GTg) [H1N1 Avian],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca15_35F_2011_01_06 (
. . . . . . . . GISAID NA EPI340878
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa35,
. . . . . . . . syn126P (CCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 263V [H1N1 Avian],
. . . . . . . . . . . . [H5N1 wt],
. . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . 269I [H5N1 (tTa)],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa454)

. . . . MoroccoCasablanca07_23F_2011_01_05 (
. . . . . . . . GISAID NA EPI340864
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . NA Truncated before aa34,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . 419S,
. . . . . . . . 420A,
. . . . . . . . 428I,
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca210_2010_12_20 (
. . . . . . . . GISAID NA EPI340886
. . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa17,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn273N (AAc) [H1N1 Avian],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa457)

Supporting Sequences

. . . . NewYork7420_2010_01_02 (
. . . . . . . . GenBank HA CY065067
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . 35I [H5N1 Egypt Human 2009-2010],
. . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . syn80S (TCt) [H5N1 Egypt Human 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H6N1, H7N3, H9N2, H11],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with #1T, 8V, 22I, syn31H,
. . . . . . . . . . . . . . . . . . . . . . . . syn40H, syn42G, 72L,
. . . . . . . . . . . . . . . . . . . . . . . . syn81Y, syn82I, 87N
. . . . . . . . . . . . . . . . . . . . . . . . syn118E, 144E, 158E,
. . . . . . . . . . . . . . . . . . . . . . . . 189T, 200T, 218S, 218V,
. . . . . . . . . . . . . . . . . . . . . . . . 237I, syn287G, syn346G,
. . . . . . . . . . . . . . . . . . . . . . . . 453K, 502K, 523A, 523I],
. . . . . . . . syn159N (AAc) [H3N8 Avian & Equine],
. . . . . . . . . . . . . . . [H9N2],
. . . . . . . . syn184H (CAc) [Early pH1N1 Highly Zoonotic]
. . . . . . . . . . . . . . . . . . [swine pH1N1.Clade5],
. . . . . . . . . . . . . . . . . . [H2N3, H3N8],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Fatality 2010],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2009],
. . . . . . . . . . . . . . . . . . [H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . 236I [H3N8],
. . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . [H5N1 Egypt Avian 2008-2010],
. . . . . . . . . . . . [H6, H7N7, H9N2 2009, H11],
. . . . . . . . syn413K (AAg) [H1N1 Avian, H2, H5N1, H9N2],
. . . . . . . . syn441H (CAt) [H1N1 Avian, H2, H5N1, H6, H9N2, H11])

. . . . NewYork7425_2009_12_20 (
. . . . . . . . GenBank HA CY065091
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . 35I [H5N1 Egypt Human 2009-2010],
. . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . syn113S (TCg) [1918],
. . . . . . . . syn159N (AAc) [H3N8 Avian & Equine],
. . . . . . . . . . . . . . . [H9N2],
. . . . . . . . syn184H (CAc) [Early pH1N1 Highly Zoonotic]
. . . . . . . . . . . . . . . . . . [swine pH1N1.Clade5],
. . . . . . . . . . . . . . . . . . [H2N3, H3N8],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Fatality 2010],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2009],
. . . . . . . . . . . . . . . . . . [H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . 236I [H3N8],
. . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . [H5N1 Egypt Avian 2008-2010],
. . . . . . . . . . . . [H6, H7N7, H9N2 2009, H11],
. . . . . . . . syn413K (AAg) [H1N1 Avian, H2, H5N1, H9N2],
. . . . . . . . syn441H (CAt) [H1N1 Avian, H2, H5N1, H6, H9N2, H11])

. . . . Texas43242018_2009_07_24 (
. . . . . . . . GenBank HA CY051823
. . . . . . . . 5 Polymorphisms (0 Amino and 5 Silent)
. . . . . . . . syn184H (CAc) [Early pH1N1 Highly Zoonotic]
. . . . . . . . . . . . . . . . . . [swine pH1N1.Clade5],
. . . . . . . . . . . . . . . . . . [H2N3, H3N8],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Fatality 2010],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2009],
. . . . . . . . . . . . . . . . . . [H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . syn239P (CCt) [H1N1 Avian],
. . . . . . . . syn297N (AAc) [H3N2 Asia Avian 1975-1977 with 159S, 453K],
. . . . . . . . . . . . . . . . . . [H3N8 Avian],
. . . . . . . . . . . . . . . . . . [H5N1],
. . . . . . . . . . . . . . . . . . [H9N2 Human, Avian, Equine and Seal wt],
. . . . . . . . . . . . . . . . . . [H9N2 Avian 2009],
. . . . . . . . syn453R (AGg) [H1N1 Avian],
. . . . . . . . syn525S (AGc) [H1N1 Avian])

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