HA 230I Cross-Linked in Slovakia on Transmissible Background

Last Updated
2011-02-09

The UK National Institute for Medical Research published a group of sequences on 2010-12-30 at GISAID.  One group originated from the National Public Health Institute of Slovakia.

An unusual and persistent background pivoting around 8 polymorphisms on 5 sequences arose during March 2010 in Slovakia pairing two silent polymorphisms for the first time (syn23L and syn177L (CTt)). The Slovakian sequences are all cross-linked with the HA syn413K and the NA syn407V.

Of particular interest is the Slovakia1625_56X_2010_03_30_xL from a 56 year old of unspecified gender due to the 9th polymorphism, a very rare HA 230I.  As of this deposit, the multiple backgrounds that are permissive to the HA 230I change extends to a new platform that appears to transmit (5 geographically similar sequences in 5 days).

GeneWurx has prepared an Excel spreadsheet investigating potential genetic acquisition in the currently uncharted severe Pandemic H1N1 wave in the UK.  In Version 1 of this spreadsheet, the Slovakian 230I sequence takes Column U and provides homology to one UK White Chapel sequence of interest.

GeneWurx_UK_December_Emerging_Genetics_v1.xls

. . . . Slovakia1625_56X_2010_03_30_xL (
. . . . . . . . syn23L,
. . . . . . . . 100N,
. . . . . . . . syn177L (CTt),
. . . . . . . . syn216E,
. . . . . . . . 230I (ATa),
. . . . . . . . 324I,
. . . . . . . . syn400F,
. . . . . . . . syn413K,
. . . . . . . . 461E [UKEngland712_2009_09 with 24K])

. . . . Slovakia1623_39X_2010_03_30_xL (
. . . . . . . . syn23L,
. . . . . . . . 100N,
. . . . . . . . syn177L (CTt),
. . . . . . . . syn216E,
. . . . . . . . 324I,
. . . . . . . . syn400F,
. . . . . . . . syn413K,
. . . . . . . . 452I,
. . . . . . . . 461E [UKEngland712_2009_09 with 24K])

. . . . Slovakia1624_61X_2010_03_30_xL (
. . . . . . . . syn23L,
. . . . . . . . 100N,
. . . . . . . . syn177L (CTt),
. . . . . . . . syn216E,
. . . . . . . . 324I,
. . . . . . . . syn400F,
. . . . . . . . syn413K,
. . . . . . . . 461E [UKEngland712_2009_09 with 24K])

. . . . Slovakia1626_59X_2010_03_30_xL (
. . . . . . . . syn23L,
. . . . . . . . 100N,
. . . . . . . . syn177L (CTt),
. . . . . . . . syn216E,
. . . . . . . . 324I,
. . . . . . . . syn400F,
. . . . . . . . syn413K,
. . . . . . . . 461E [UKEngland712_2009_09 with 24K])

. . . . Slovakia1634_42X_2010_04_03_xL (
. . . . . . . . syn23L,
. . . . . . . . 100N,
. . . . . . . . syn177L (CTt),
. . . . . . . . syn216E,
. . . . . . . . 324I,
. . . . . . . . syn400F,
. . . . . . . . syn413K,
. . . . . . . . 461E [UKEngland712_2009_09 with 24K])

Supporting Sequences

. . . . UKEngland712_2009_09 (
. . . . . . . . 24K,
. . . . . . . . syn413K,
. . . . . . . . syn456L,
. . . . . . . . 461E [Slovakia1625_56X_2010_03_30_xL with 230I])

. . . . DenmarkHvidovreINS141_2009_11_20_xL (
. . . . . . . . syn23L,
. . . . . . . . syn238E,
. . . . . . . . 324I,
. . . . . . . . syn413K,
. . . . . . . . syn484N,
. . . . . . . . syn549R)

. . . . Victoria508_2010_07_24 (
. . . . . . . . 35I [H5N1],
. . . . . . . . 88P [H2N3, H5N1, H11],
. . . . . . . . . . . [HunanHechengSWL1616_2009-11-23,
. . . . . . . . . . . KoreaAF2376_2009_10_27
. . . . . . . . . . . . . . . with 280A and 290K],
. . . . . . . . syn102E [SingON2407_2009_12_13,
. . . . . . . . . . . . . . . Singapore544_2009_12_10,
. . . . . . . . . . . . . . . Brussels243_2009_11_09
. . . . . . . . . . . . . . . . . . . . with syn44L and 89G],
. . . . . . . . syn152I [CalifVRDL115_2009_12_04,
. . . . . . . . . . . . . . . NY6939_2009_12_11,
. . . . . . . . . . . . . . . tkOntarioFAV117_1C_2009_12_07
. . . . . . . . . . . . . . . . . . . . with 35I, syn219I, syn276H, syn456L, 463V, 523A,
. . . . . . . . . . . . . . . England1050_2009_12,
. . . . . . . . . . . . . . . Scotland103_2009_12,
. . . . . . . . . . . . . . . England1051_2009_12,
. . . . . . . . . . . . . . . ItalyAncona451_2009_11_27_f,
. . . . . . . . . . . . . . . NY6607_2009_11_24,
. . . . . . . . . . . . . . . CalifVRDL107_2009_11_15,
. . . . . . . . . . . . . . . CalifVRDL101_2009_11_05,
. . . . . . . . . . . . . . . DC_114_2009_11_04,
. . . . . . . . . . . . . . . England94800096_2009_11,
. . . . . . . . . . . . . . . Calif_SD35_2009_10_26,
. . . . . . . . . . . . . . . NY5447_2009_10_23,
. . . . . . . . . . . . . . . CalifVRDL84_2009_10_09,
. . . . . . . . . . . . . . . CalifVRDL87_2009_10_09,
. . . . . . . . . . . . . . . IndiaPune6196_2009_08,
. . . . . . . . . . . . . . . IndiaDhule9433_2009_08,
. . . . . . . . . . . . . . . SantoDomingoWR1057N_2009_07_02,
. . . . . . . . . . . . . . . SantoDomingoWR1058N_2009_07_02,
. . . . . . . . . . . . . . . SantoDomingoWR1059N_2009_06_30],
. . . . . . . . 206S,
. . . . . . . . syn219I [CalifVRDL115_2009_12_04
. . . . . . . . . . . . . . . . . with 35I, syn152I, syn276H, syn456L, 463V, 523A,
. . . . . . . . . . . . . . FL_Pen213_2009_11_17
. . . . . . . . . . . . . . . . . . . . with 35I, syn152I, 273A, syn456L, 463V, 523A,
. . . . . . . . . . . . . . CalifVRDL107_2009_11_15
. . . . . . . . . . . . . . . . . . . . with 35I, syn152I, syn276H, syn456L, 463V, 523A,
. . . . . . . . 238D (GAc) [H2N3, H7N3, H7N7],
. . . . . . . . . . . . . . . . . . [Belgorod2_2010-03-15 (GAt),
. . . . . . . . . . . . . . . . . . Kaliningrad01_2009_11_02 (GAt)
. . . . . . . . . . . . . . . . . . . . . . . . with 225E and 226R,
. . . . . . . . . . . . . . . . . . AthensINS398_2010-01-24 GAt),
. . . . . . . . . . . . . . . . . . KaliningradCRIE_DA_2009-09-26 (GAt),
. . . . . . . . . . . . . . . . . . KaliningradCRIE_KG_2009-09-25 (GAt),
. . . . . . . . . . . . . . . . . . KaliningradCRIE_MA_2009-09-25 (GAt),
. . . . . . . . . . . . . . . . . . KaliningradCRIE_SHD_2009-09-25 (GAt),

. . . . . . . . . . . . . . . . . . KaliningradCRIE_ZD_2009-09-25 (GAt)],
. . . . . . . . syn247A [Belize8756_2009_10_08,
. . . . . . . . . . . . . . . Singapore93_2009_06_22]
. . . . . . . . syn254P,
. . . . . . . . 272G [Niigata19_2009_12_31,
. . . . . . . . . . . . GuangdongSWL36_2009_11_29],
. . . . . . . . syn276H,
. . . . . . . . syn388K [H5N1],
. . . . . . . . . . . . . . . [NagasakiHA_10_28_2010_03_23
. . . . . . . . . . . . . . . . . . . . . with 22I,
. . . . . . . . . . . . . . . NagasakiHA_10_26_2010_03_15
. . . . . . . . . . . . . . . . . . . . . with 22I, syn103E,
. . . . . . . . . . . . . . . NagasakiHA_10_24_2010_03_08
. . . . . . . . . . . . . . . . . . . . . with syn103E,
. . . . . . . . . . . . . . . GuangxiLonganSWL1990_2010_02_08
. . . . . . . . . . . . . . . . . . . . . with 453K, syn462E,
. . . . . . . . . . . . . . . JiangxiDonghuSWL15_2010_01_04
. . . . . . . . . . . . . . . . . . . . . with syn106E, 149R, syn456L (TTg),
. . . . . . . . . . . . . . . ViennaINS142_2009_11_26
. . . . . . . . . . . . . . . . . . . . . with syn97D, 99T,
. . . . . . . . . . . . . . . CzechUsti208_2009_11_25
. . . . . . . . . . . . . . . . . . . . . with 268T,
. . . . . . . . . . . . . . . GhanaFS_1921_2009_11_11,
. . . . . . . . . . . . . . . Alaska44_2009_11_17
. . . . . . . . . . . . . . . . . . . . . with syn275V, 276N,
. . . . . . . . . . . . . . . CalifVRDL76_2009_09_21
. . . . . . . . . . . . . . . . . . . . . with syn283Q,
. . . . . . . . . . . . . . . Taiwan206_2009_09_18,
. . . . . . . . . . . . . . . Taiwan177_2009_09_18,
. . . . . . . . . . . . . . . Taiwan167_2009_09_18,
. . . . . . . . . . . . . . . Taiwan156_2009_09_18,
. . . . . . . . . . . . . . . Taiwan143_2009_09_15
. . . . . . . . . . . . . . . . . . . . . with 205E mix,
. . . . . . . . . . . . . . . Utah20_C2_2_2009_07_25_VxX
. . . . . . . . . . . . . . . . . . . . . with 159D, 206S, 227G
. . . . . . . . . . . . . . . Slovenia2687_2009_07_01
. . . . . . . . . . . . . . . . . . . . . with 35I, 206S],
. . . . . . . . syn456L,
. . . . . . . . 463V,
. . . . . . . . 523A [Nebraska02_2010_03_11,
. . . . . . . . . . . . NagasakiHA1022_2010_03_01_syn413K,
. . . . . . . . . . . . DomRepublic3768_2009_12_15,
. . . . . . . . . . . . NY6939_2009_12_11,
. . . . . . . . . . . . CalifVRDL115_2009_12_04,
. . . . . . . . . . . . NY6607_2009_11_24,
. . . . . . . . . . . . RheinlandPfalz81_2009_11_23,
. . . . . . . . . . . . Berlin210_2009_11_16,
. . . . . . . . . . . . BadenWurttemberg511_2009_11_16,
. . . . . . . . . . . . CalifVRDL107_2009_11_15,
. . . . . . . . . . . . FL_Pensacola40_2009_11_09,
. . . . . . . . . . . . CalifVRDL101_2009_11_05,
. . . . . . . . . . . . DC114_2009_11_04,
. . . . . . . . . . . . Calif_SD35_2009_10_26,
. . . . . . . . . . . . NY5447_2009_10_23,
. . . . . . . . . . . . CalifVRDL84_2009_10_09,
. . . . . . . . . . . . CalifVRDL87_2009_10_09,
. . . . . . . . . . . . KuwaitN13013_2009_08_31_syn413K]),

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HA 225G Paired with 156E & 188T in Diverse Deposit from Australia

Last Updated 2010-12-16

A WHO Collaborating Centre for Reference and Research on Influenza released a large group of sequences at GISAID on 2010-12-14 primarily from Australia. 225G appears on two different backgrounds during the same timeframe, one with the H7N7 polymorphism that has been associated with viral conjunctivitis, 188T.  OzBrisbane209_51F_2010_08_09 also demonstrates a 156E polymorphism just upstream from the section at aa158 and aa159 that has produced so many "Low Reactor" / Vaccine Escape strains.

156E was found in the 1976 Swine Flu with 225G, but until now has not been documented in the pH1N1 with 225G, though the individual change has been located in 9 sequences [New Zealand, Japan (2), China 2010, Hungary, Germany (2) and the United States (2)].  Changes at residues 156, 157 and 158 are known to increase viral replication speed and success on the pandemic H1N1 background.  At the MedImmune growth speed experiments preparing for the 2009 Live Attenuated Influenza Vaccine, the combination of 156E and 225G created the highest pathological output (V5-153E) (J Virol. 2010 January; 84(1): 44–51). Though the V5-153E strain produced the most beneficial viral output, the lineage was impeached due to a 16 fold titers reduction in the antigenicity tests indicating a profound level of "Low Reactor".
 
This Brisbane sample has not yet been tagged for Vaccine Escape.

As a set of coincident events, several zoonotic Influenza reservoirs have also gained 156E in recent years.  This group of reservoirs appears to parallel individual changes coming into the human H1N1 pandemic.  H5N1 human cases in Vietnam carry this change from 2004.  The most current updates of Avian sequences from Egypt H5N1 in 2009 up to July 2010 demonstrate emergent 156E with 225G (Ggg).  One particular Egyptian bird, ckEgypt10135ss_2010_03, shows 156E, 225G and a variant coding for syn338G (GGg).

H3N8 equine and swine samples are on record producing this emergent change.  H7N3 and H7N7 each provide material for nucleotide donation at the first codon base while an extensive percentage of the H10N7 sequences on file carry the 156E.  A hybrid swine H1N1 sequence from Iowa,
swIowa44837_1_2009_11_08_xL, was recently published after a one year lag with 156E, 188R, 225N, 230I & syn346G.

This Brisbane strain is emergent and aggregates 225G with markers found throughout the coastal United States during late 2009 and 2010.  On a similar note, a sub-clade may perhaps be forming from Jiangsu Province, China using 225G paired with 158E and a change at amino acid position 454.

The 215T found in the sequence from the 9 year old boy, Sydney202_9M_2010_07_18, confirms an increase in the genetic diversity of the post-pandemic reservoir found during the official pandemic on an eastern European sequence, PolandWarsawINS316_2009_12_08.

As we have previously reported, 100% of the Hemagglutinin positions between 186 and 248, including antigenic areas of the Receptor Binding Domain (RBD/RBS), are on record as polymorphic. No position in that range is stable.  Many positions rate multiple changes.  Protein revision is documented at 60 of the 63 positions (95%), engaging the potential for antibody resistance (natural immune escape and vaccine escape). 

. . . . OzBrisbane209_51F_2010_08_09 (
. . . . . . . . 156E [H2N3, H3N8, H5N1, H10N7],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . 225G,
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . . . . . . . . [OzVictoria670_30M_2010_11_14
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . Emergent across Australia
. . . . . . . . . . . . . . . . . . . . . during late 2010 season,
. . . . . . . . . . . . . . . Florida14_24M_2010_08_05
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . OZVictoria512_2010_07_30
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . NZChristchurch15_2010_07_12
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . India5107_2010_06_28
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . MississippiAF2474_2010_03_10
. . . . . . . . . . . . . . . . . . . . . with syn235T,
. . . . . . . . . . . . . . . FloridaAF2197_2010_03_07
. . . . . . . . . . . . . . . . . . . . . with 156T,
. . . . . . . . . . . . . . . CalifVRDL9_2010_02_09
. . . . . . . . . . . . . . . . . . . . . with syn193S,
. . . . . . . . . . . . . . . Georgia06_2010_02_05
. . . . . . . . . . . . . . . . . . . . . with syn161Y,
. . . . . . . . . . . . . . . NY4662_2010_02_03
. . . . . . . . . . . . . . . . . . . . . with 97N, syn276H, syn283Q, syn304G,
. . . . . . . . . . . . . . . TexasJMS406_2010_01_10
. . . . . . . . . . . . . . . . . . . . . with 187A, syn193S, syn283Q,
. . . . . . . . . . . . . . . TexasJMS405_2010_01_09
. . . . . . . . . . . . . . . . . . . . . with 187A, syn283Q,
. . . . . . . . . . . . . . . CalifVRDL131_2009_12_30
. . . . . . . . . . . . . . . . . . . . . with 225G, syn455Q,
. . . . . . . . . . . . . . . LouisianaAF2435_2009_11_30
. . . . . . . . . . . . . . . . . . . . . with syn13N,
. . . . . . . . . . . . . . . Vienna291_2009_11_19
. . . . . . . . . . . . . . . catOregon29573_2009_11_09
. . . . . . . . . . . . . . . . . . . . . with 226R, syn283Q,
. . . . . . . . . . . . . . . Calif_SanDiegoINS63_2009_10_26
. . . . . . . . . . . . . . . . . . . . . with syn283Q, et al],
. . . . . . . . 377K,
. . . . . . . . 454N [H7N3, H7N7, H9N2]
. . . . . . . . . . [Florida14_24M_2010_08_05
. . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . FL_Pen210_2009_11_10
. . . . . . . . . . . . . . . . . . with 225E,
. . . . . . . . . . SouthCarolina18_2009_09_16_VxX
. . . . . . . . . . . . . . . . . . with 159D, 224K,
. . . . . . . . . . Texas45131774_2009_09_13
. . . . . . . . . . . . . . . . . . with syn223V,
. . . . . . . . . . IndiaPune9355_2009_08
. . . . . . . . . . . . . . . . . . with 225G,
. . . . . . . . . . IndiaBlore236_2009_06_xL
. . . . . . . . . . . . . . . . . . with 226R, et al],
. . . . . . . . syn465N)

. . . . Sydney202_9M_2010_07_18 (
. . . . . . . . 34D,
. . . . . . . . syn44L,
. . . . . . . . 97N,
. . . . . . . . syn106E,
. . . . . . . . 128D,
. . . . . . . . 215T [PolandWarsawINS316_2009_12_08]
. . . . . . . . 225G,
. . . . . . . . 253A,
. . . . . . . . syn362S,
. . . . . . . . 377K,
. . . . . . . . 439G [Guangdong5024_2009_10_20])

Supporting Sequences

. . . . Florida14_24M_2010_08_05 (
. . . . . . . . 100N [H7N3, H7N7, H9N2],
. . . . . . . . syn161Y [H3N8 2009, H6N1, H9N2],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 442I mix,
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . OZVictoria512_2010_07_30 (
. . . . . . . . syn60I,
. . . . . . . . 100N [H7N3, H7N7, H9N2],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn285P,
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . Thailand34_9912_2010_07_14 (
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . 200T,
. . . . . . . . HA truncated after aa253)

. . . . Thailand34_9937_2010_07_14 (
. . . . . . . . 162Q [Unique to PF11 GenBank/GISAID],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . HA truncated after aa253)

. . . . NZChristchurch15_2010_07_12 (
. . . . . . . . 100N,
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . India5107_2010_06_28 (
. . . . . . . . syn60I,
. . . . . . . . 100N [H7N3, H7N7, H9N2],
. . . . . . . . syn135V,
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . India8910_2010_05_08 (
. . . . . . . . syn49G [H7N3, H7N7],
. . . . . . . . syn51A,
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . swThaiCURA75_2010_01 (
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . 263D,
. . . . . . . . syn350G [H7N3, H7N7],
. . . . . . . . 414I,
. . . . . . . . syn484N [H3N8, H4, H5N1 (E/A/H), H6, H7N7, H9N2, H11])

. . . . Texas45131774_2009_09_13 (
. . . . . . . . syn223V [H5N1, H6N1],
. . . . . . . . 454N [H7N3, H7N7, H9N2]
. . . . . . . . . . . . . . [IndiaPune9355_2009_08 with 225G,
. . . . . . . . . . . . . . IndiaBlore236_2009_06 with 226R,
. . . . . . . . . . . . . . SouthCarolina18_2009_09_16_VxX with 224K,
. . . . . . . . . . . . . . FL_Pen210_2009_11_10 with 225E])

. . . . PolandWarsawINS316_2009_12_08 (
. . . . . . . . 22I,
. . . . . . . . syn92T,
. . . . . . . . 119M,
. . . . . . . . 165N,
. . . . . . . . syn178V,
. . . . . . . . syn186S,
. . . . . . . . 215T,
. . . . . . . . syn256Y,
. . . . . . . . syn275V,
. . . . . . . . 463V)

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HA 225G with 158E Series in Jiangsu China

Last Updated 2010-12-15

The Jiangsu Provincial Center for Disease Prevention and Control released a small set of sequences at GenBank on 2010-12-06 from the late 2009 pH1N1 reservoir. These sequences are related to several of the most recent and most concerning Chinese sequences on file that also came from Jiangsu. In an unusual presentation, the early sequences appear to be more elaborate genetically than the later group. Are we seeing the PF11 reservoir select the most useful revisions to continue attacking humans while dropping extraneous or sub-optimal genetic material? 

Recall that the Ukraine produced an early Vaccine Escape strain, UkrLvivN6_26M_2009_10_27_xL_VxX_f, that carried only one amino acid change, 225G, and one silent change, syn413K.  A variant passage of that same UkrLvivN6 patient created a sequence, UkrLvivN6_2009_10_27_C3C1_xL_f, with an additional amino acid change producing the following polymorphisms.

UkrLvivN6_2009_10_27_C3C1_xL_f

• 158E
• 225G
• syn413K (AAg) - synonymous cross-linkage (xL) marker

The 158E and 225G amino acid combination came to be of interest to GeneWurx due to the variant sub-species produced from this Ukrainian sample. As additional sequences emerged in a similar geography including RussiaBelgorod2_2010_03_15 as predicted with 230I, emergent behaviour around these amino acid positions was noted for closer surveillance and the diverse nucleotide coding for 225G (Gga) from an overlay of 225G (GgT) onto a 225E (GAa) substrate was packaged onto the corresponding watch list.

The Chinese sequences discussed today have a limited set of metadata, and are perhaps more highly correlated than they appear. A slight possibility for duplicate submission exists. Six geographically-sited sequences with this type of combination is a set worthy of investigation. Although some potential exists for errors in the names and dates of these Chinese sequences, the data at hand suggests that a sub-clade may be emerging in the Jiangsu region with five polymorphisms traveling together in a group that boasts rarity and Vaccine Escape documentation.

Jiangsu province is on the east coast of China and boasts the highest population density of any province in the country. Water covers 18% of the province with another 68% as low-lying plains. Jiangsu is also known as the “land of water” due to a thousand kilometer coast line with the Yellow Sea, the Yangtze River passing through the south, an extensive irrigation system and the canals found throughout several of the cities. Nanjing, the capital, is situated within the Yangtze River Delta. [Jiangsu, Nanjing]

With this deposit, polymorphisms at amino acid position 454 may now be correlated with RBD changes. An affinity exists in the aa223 to aa226 range and with HA 188T. These Chinese sequences carry the 158E revision that is useful for infecting the human upper respiratory tract and the 225G that is equally as useful in deep lung infection.

The recent 230I bearing sequence from Russia also demonstrates that 158E and 225G combination.  A more current sequence from Australia, OzBrisbane209_51F_2010_08_09, shows a tendency toward this framing via domaining with 156E and matching the 225G while also carrying the H7N7 viral conjunctivitis-correlated polymorphism of HA 188T.  Perhaps the SNP coding for the Southern Hemisphere 156E will be discovered in the animal reservoir of H7N7 or H9N2, paralleling the potential donor pools for 188T and 454N onto the human pandemic.

Declaration of Pandemic conclusion via press release has not effectively prevented emergent behaviour in this zoonoticly-active disease reservoir.  Influenza Flux is apparently ongoing as the world remains in a pre-PF11_Ω phase. 

An enterprising question might be, “How many Hydra strains of Vaccine Escape capacity will co-circulate in this Northern Hemisphere winter?”

. . . . ChinaJiangsuNanjing1_2010_06_30 (
. . . . . . . . 131P,
. . . . . . . . 158E [H3N8, H5N1],
. . . . . . . . 225G,
. . . . . . . . 454G [Unique to PF11 Jiangsu],
. . . . . . . . 488N [H3N8 2009, H6, H9N2, NewJersey01_2010_01_01])

. . . . ChinaJiangsuNanjing2_2010_06_30 (
. . . . . . . . 131P,
. . . . . . . . 158E [H3N8, H5N1],
. . . . . . . . 225G,
. . . . . . . . 454G [Unique to PF11 Jiangsu],
. . . . . . . . 488N [H3N8 2009, H6, H9N2, NewJersey01_2010_01_01])

. . . . ChinaJiangsu1_2009_11_20_re (
. . . . . . . . 131P,
. . . . . . . . 158E [H3N8, H5N1],
. . . . . . . . 225G,
. . . . . . . . 454G [Unique to PF11 Jiangsu],
. . . . . . . . 488N [H3N8 2009, H6, H9N2, NewJersey01_2010_01_01])

. . . . ChinaJiangsu2_2009_11_13_re (
. . . . . . . . 131P,
. . . . . . . . 158E [H3N8, H5N1],
. . . . . . . . 225G,
. . . . . . . . 454G [Unique to PF11 Jiangsu],
. . . . . . . . 488N [H3N8 2009, H6, H9N2, NewJersey01_2010_01_01])

. . . . ChinaJiangsuS61_2009_11_10 (
. . . . . . . . 54R,
. . . . . . . . 84G [Unique to GenBank PF11],
. . . . . . . . 131P,
. . . . . . . . 158E [H3N8, H5N1],
. . . . . . . . 211R [swOR4060_2009_12_31],
. . . . . . . . 225G,
. . . . . . . . syn319T [MississippiAF2473_2010_03_04 with 60T, 225E,
. . . . . . . . . . . . . . . FloridaAF2199_2010_03_11 with 60T, 225E,
. . . . . . . . . . . . . . . YaroslavlIIV196_2009_12_04_f with 225G
. . . . . . . . . . . . . . . SpainCatS1236_2009_08_13 with 225E,
. . . . . . . . . . . . . . . Finland612_2009_07_21 with 225E,
. . . . . . . . . . . . . . . KazAstana818_2009_07,
. . . . . . . . . . . . . . . KazAlmati01_2009 with 225E],
. . . . . . . . 454G [Unique to PF11 Jiangsu],
. . . . . . . . 488N [H3N8 2009, H6, H9N2, NewJersey01_2010_01_01])

. . . . ChinaJiangsuS62_2009_11_10 (
. . . . . . . . 60T [MississippiAF2473_2010_03_04 with 225E, syn319T,
. . . . . . . . . . . FloridaAF2199_2010_03_11 with 225E, syn319T],
. . . . . . . . 131P,
. . . . . . . . 158E [H3N8, H5N1],
. . . . . . . . 225G,
. . . . . . . . 454G [Unique to PF11 Jiangsu],
. . . . . . . . 481G,
. . . . . . . . 488N [H3N8 2009, H6, H9N2, NewJersey01_2010_01_01])

Supporting Sequences

. . . . RussiaBelgorod2_2010_03_15 (
. . . . . . . . syn13N [WiscD0459_2009_12_18_xL
. . . . . . . . . . . . . . . . . . with 189T, 324I & 499K,
. . . . . . . . . . . . . . LouisianaAF2435_2009_11_30
. . . . . . . . . . . . . . . . . . with syn338G],
. . . . . . . . 77N [tn, swine, S5]
. . . . . . . . . . . [JapanOsaka60_2010_07_02
. . . . . . . . . . . . . . . . with syn276H,
. . . . . . . . . . . Maryland04_2010_02_08
. . . . . . . . . . . . . . . . with syn276H,
. . . . . . . . . . . ShandongShizhongSWL24_2010_01_24,
. . . . . . . . . . . NY7020_2009_12_14
. . . . . . . . . . . . . . . . with syn166K & 189T,
. . . . . . . . . . . CalifVRDL115_2009_12_04
. . . . . . . . . . . . . . . . with syn276H,
. . . . . . . . . . . JapanAF2267_2009_11_09
. . . . . . . . . . . . . . . . with 286E,
. . . . . . . . . . . NevadaAF2490_2009_11_02
. . . . . . . . . . . . . . . . with 100N & syn270I,
. . . . . . . . . . . AlaskaAF2093_2009_11_02
. . . . . . . . . . . . . . . . with 286E,
. . . . . . . . . . . Russia74_2009_11_01_xL,
. . . . . . . . . . . ThailandTHB0441_2009_07_28,
. . . . . . . . . . . Lisboa40_2009_06_23,
. . . . . . . . . . . AnhuiSWL1_2009_06_18
. . . . . . . . . . . . . . . . with 275I,
. . . . . . . . . . . Lithuania1942_2009,
. . . . . . . . . . . swKoreaSCJ10_2009_12,
. . . . . . . . . . . swKoreaSCJ09_2009_12]
. . . . . . . . 158E mix,
. . . . . . . . 225G (Gga) stepwise from 225E,
. . . . . . . . 230I (ATa),
. . . . . . . . 238D [H2N3, H7N3, H7N7, tn, swine],
. . . . . . . . . . . . [PNG_Goroka17_2010_04_14,
. . . . . . . . . . . . AthensINS398_2010_01_24,
. . . . . . . . . . . . AthensINS339_2009_12_30,
. . . . . . . . . . . . Kaliningrad01_11M_2009_11_02
. . . . . . . . . . . . . . . . . . with 225E & 226R,
. . . . . . . . . . . . KaliningradCRIE_DA_2009_09_26,
. . . . . . . . . . . . KaliningradCRIE_KG_2009_09_25,
. . . . . . . . . . . . KaliningradCRIE_SHD_2009_09_25,
. . . . . . . . . . . . KaliningradCRIE_MA_2009_09_25,
. . . . . . . . . . . . KaliningradCRIE_ZD_2009_09_25],
. . . . . . . . syn245F [H2N3, H5N1, H7N7, H10N7, H11]
. . . . . . . . . . . . . . [SingON2416_2009_12_15
. . . . . . . . . . . . . . . . . . . . . with syn166K & 300P,
. . . . . . . . . . . . . . . EgyptAswan2288_2009_11_02
. . . . . . . . . . . . . . . . . . . . . with 189T],
. . . . . . . . 300S [H7N3, H7N7 (tCt)],
. . . . . . . . 305N (AAc) [ThaiChiangRai226_2M_2010_03_04
. . . . . . . . . . . . . . . . . . . . . . . with 270T,
. . . . . . . . . . . . . . . . . . Brunei5_52M_2010,
. . . . . . . . . . . . . . . . . . SouthCarolinaAF2562_2009_11_15 (AAt),
. . . . . . . . . . . . . . . . . . DenmarkAalborgINS133_2009_12_02 (AAt)],
. . . . . . . . syn343G [H3N8, H5N1, H6N1, H7N3, H7N7, H10N7, H11, 1918],
. . . . . . . . . . . . . . . [Thuringen189_2009_11_24_xL,
. . . . . . . . . . . . . . . Thuringen227_11_17_xL])

. . . . Brisbane209_51F_2010_08_09 (
. . . . . . . . 156E,
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . 225G,
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . . . . . . . . [Victoria670_30M_2010_11_14
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . Emergent across Australia
. . . . . . . . . . . . . . . . . . . . . during late 2010 season,
. . . . . . . . . . . . . . . Florida14_24M_2010_08_05
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . OZVictoria512_2010_07_30
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . NZChristchurch15_2010_07_12
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . India5107_2010_06_28
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . MississippiAF2474_2010_03_10
. . . . . . . . . . . . . . . . . . . . . with syn235T,
. . . . . . . . . . . . . . . FloridaAF2197_2010_03_07
. . . . . . . . . . . . . . . . . . . . . with 156T,
. . . . . . . . . . . . . . . CalifVRDL9_2010_02_09
. . . . . . . . . . . . . . . . . . . . . with syn193S,
. . . . . . . . . . . . . . . Georgia06_2010_02_05
. . . . . . . . . . . . . . . . . . . . . with syn161Y,
. . . . . . . . . . . . . . . NY4662_2010_02_03
. . . . . . . . . . . . . . . . . . . . . with 97N, syn276H, syn283Q, syn304G,
. . . . . . . . . . . . . . . TexasJMS406_2010_01_10
. . . . . . . . . . . . . . . . . . . . . with 187A, syn193S, syn283Q,
. . . . . . . . . . . . . . . TexasJMS405_2010_01_09
. . . . . . . . . . . . . . . . . . . . . with 187A, syn283Q,
. . . . . . . . . . . . . . . CalifVRDL131_2009_12_30
. . . . . . . . . . . . . . . . . . . . . with 225G, syn455Q,
. . . . . . . . . . . . . . . LouisianaAF2435_2009_11_30
. . . . . . . . . . . . . . . . . . . . . with syn13N,
. . . . . . . . . . . . . . . Vienna291_2009_11_19
. . . . . . . . . . . . . . . catOregon29573_2009_11_09
. . . . . . . . . . . . . . . . . . . . . with 226R, syn283Q,
. . . . . . . . . . . . . . . Calif_SanDiegoINS63_2009_10_26
. . . . . . . . . . . . . . . . . . . . . with syn283Q, et al],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2],
. . . . . . . . . . [Florida14_24M_2010_08_05
. . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . FL_Pen210_2009_11_10
. . . . . . . . . . . . . . . . . . with 225E,
. . . . . . . . . . SouthCarolina18_2009_09_16_VxX
. . . . . . . . . . . . . . . . . . with 159D, 224K,
. . . . . . . . . . Texas45131774_2009_09_13
. . . . . . . . . . . . . . . . . . with syn223V,
. . . . . . . . . . IndiaPune9355_2009_08
. . . . . . . . . . . . . . . . . . with 225G,
. . . . . . . . . . IndiaBlore236_2009_06_xL
. . . . . . . . . . . . . . . . . . with 226R, et al],
. . . . . . . . syn465N)

Please visit GeneWurx.com for insight into the latest published studies.

HA 223E and 223M in Early Pandemic Suggest Correlation to H5N1 and H3N8 Polymorphisms

On 2010-11-29, a WHO Collaborating Centre for Reference and Research on Influenza deposited an aged sequence from an early Dalby pH1N1 sample, 2009-08-27, originated at the Queensland Health Scientific Services of Australia. The OzBrisbane2014_2009_08_27 sequence was published with no age, gender, antigenic characterisation or drug resistance information.

OzBrisbane2014_2009_08_27 carries a very early genetic revision in the Receptor Binding Domain just upstream of the much discussed amino acid position 225. The 223E on this sequence marks a novel instance at a position with very few recorded changes (223M).  This viral reservoir began to cycle through tested Immune Escape RBD changes at a very young age, though this data has only recently been made public. Protein revision is documented at 58 of the 63 amino acid positions (92%) within a critical Receptor Binding Domain area slotting from 186 to 248.

Zoonotic Influenza serotypes have also demonstrated changes corresponding to amino acid position 223, in animals and in humans.

H3N8 is consistently 223V, matching the amino acid value in the pH1N1 reservoir, except for two recent equine sequences from 2008 Egypt [eqEgypt6066NAMRU3VSVRI_2008] and 2009 Japan [eqYokohamaaq19_2009] that each revised at the first nucleotide from G to A, gTC->aTC producing 223I, Isoleucine.

H5N1 is also consistently 223V, except in a very small number of cases that show a similar first base revision of G to A, gTA->aTA producing also 223I, Isoleucine. These H5N1 cases with a revision at amino acid position 223 include at least 2 of the 2006 Gharbiyah, Egypt human death cluster [Egypt14724_2006 & Egypt14725_2006], avian samples from 2007 Egypt [ckEgypt1892N3_HK49_2007], an adult female from 2009 in Kafr El Sheikh, Egypt [EgyptN03434_33F_2009_04_15] and 2 Viet human cases [VietCL100_2004 & VietJPHN30321_2005].

H7N3 and H7N7 are also remarkably consistent as 223V, with a similar variation to H3N8 and H5N1 on H7N7 equine samples worldwide from 1956 to 1977. These older equine samples primarily show the now familiar first base revision of G to A, gTA->aTA (15) producing 223I, Isoleucine. A parallel situation occurs in the H11 reservoir with two sequences of birds from Ohio (1987 and 2001) moving from G to A, gTA->aTA.

That same G to A first base nucleotide revision onto a Pandemic H1N1 background, gTG->aTG, may have produced the 223M found in a human pH1N1 case from California early in the pandemic, California33_2009_08_06. The potential donor for the 223E remains unresolved. The probability is very low for true mutation / sloppy polymerase being involved because patterning throughout the remainder of the sequence leads to other considerations.

Influenza Flux is not necessarily a one-way street. Today’s donor may be tomorrow’s recipient. This particular zoonotic serotype variation pattern around amino acid position 223 that is overlaying onto human pH1N1 is but the tip of the iceburg considering the inter-serotype dynamics (animal <=> human) that GeneWurx.com has carefully documented over the past 20 months.

With 2 of the most recent H5N1 human cases (Hong Kong and Indonesia) presenting several novel and important clinical signals, a meritorious investigation would determine potential pH1N1 and H5N1 genetic interaction. The creation of a lower CFR H5N1 reservoir like Egypt of 2009 and other similar H5N1 genetics may begin allowing a more consistent and longer human incubation period like these two recent “walking H5N1” patients.

A longer human incubation period, with a commensurate slower burn through the H5N1 human host, increases the potential for co-infection with pH1N1. Co-infection, especially with pH1N1, creates the distinct risk of further human adaptation. PF11 is certainly considered capable of effective transmission. Thereby, a slightly more adept human H5N1, as seen in these 2 recent cases, may further optimise H2H (Human to Human) transmission genetics for the traditional Avian Influenza serotypes.

These reservoirs appear to be working in tandem and in earnest.

. . . . OzBrisbane2014_2009_08_27 (
. . . . . . . . 3T [GhanaFS1966_2010_04-06,
. . . . . . . . . . . Taiwan27_2010_03_01
. . . . . . . . . . . . . . . .with 189T, 218T, syn305K, 404D, syn494E,
. . . . . . . . . . . NY04_2010_02_25
. . . . . . . . . . . . . . . .with 100N, syn232Y, syn270I, 437N, syn484N,
. . . . . . . . . . . England1054_2009_12 with 225E,
. . . . . . . . . . . RussiaStPeter99_2009_11_30
. . . . . . . . . . . . . . . .with 225E, syn325P,
. . . . . . . . . . . SichuanWuhouSWL4401_2009_11_29 with syn413K,
. . . . . . . . . . . MarylandAF2457_2009_11_12,
. . . . . . . . . . . Mississippi03_2009_09_25,
. . . . . . . . . . . HongKong24705_2009_09_13,
. . . . . . . . . . . Netherlands1039_2009_08_25 with 430I,
. . . . . . . . . . . California36_2009_08_22 with syn413K,
. . . . . . . . . . . Suriname7534_2009_08_13,
. . . . . . . . . . . HenanSWL14_2009_07_17 with 225E,
. . . . . . . . . . . Surinam08_2009_06_11,
. . . . . . . . . . . Surinam02_2009_06_09,
. . . . . . . . . . . CanadaQCRV1759_2009_05_07,
. . . . . . . . . . . Ireland1_2009_05],
. . . . . . . . 223E mix wt [Unique to GISAID; Unique to GenBank],
. . . . . . . . 269V,
. . . . . . . . 414I)

Supporting Sequences

. . . . OzBrisbane2015_2009_08_28 (
. . . . . . . . 97N mix wt,
. . . . . . . . 269V,
. . . . . . . . 414I)

. . . . California33_2009_08_06 (
. . . . . . . . 223M,
. . . . . . . . 262K,
. . . . . . . . 285T,
. . . . . . . . 502K [UkrTernopilN10_2009_10_28_xL_f with 225G,
. . . . . . . . . . . Oz_Victoria800_2010_06_02,
. . . . . . . . . . . SingGP2362_2010_05_18,
. . . . . . . . . . . Scandinavia (7),
. . . . . . . . . . . CalifVRDL2_2010_01_11,
. . . . . . . . . . . Michigan21_2009_08_07,
. . . . . . . . . . . SouthCarolina36_2009_09_02,
. . . . . . . . . . . SouthCarolina38_2009_09_17,
. . . . . . . . . . . Haiti534_2009_10_19,
. . . . . . . . . . . AlgeriaG2902_2009_12_09 mix with 225E,
. . . . . . . . . . . Egypt114_2009_12_06 with 225E,
. . . . . . . . . . . JapanPR1070_2009_07_10,
. . . . . . . . . . . ThailandTHB0438_2009_07_28,
. . . . . . . . . . . Jiangyin34_2009_08_16,
. . . . . . . . . . . GuangxiLongan1870_2009_12_16])

. . . . swAlbertaOTH33_24_2009_05_03 (
. . . . . . . . 196H,
. . . . . . . . syn216E [H9N2],
. . . . . . . . 223M,
. . . . . . . . syn456L [H5N1])

. . . . swAlbertaOTH33_21_2009_05_05 (
. . . . . . . . 68R,
. . . . . . . . 223M,
. . . . . . . . 299V)

. . . . NY04_2010_02_25 (
. . . . . . . . 3T [OzBrisbane2014_2009_08_27, et al],
. . . . . . . . 50E,
. . . . . . . . syn53L [H2, H5N1 Viet Human, Avian, Civet, H6N1],
. . . . . . . . . . . . . . [TexasJMS380_2009_11_27 with 25R,
. . . . . . . . . . . . . . Tambov_SPN_2009_11_24_f with 225N],
. . . . . . . . 100N,
. . . . . . . . syn232Y,
. . . . . . . . syn270I,
. . . . . . . . 377K,
. . . . . . . . 437N,
. . . . . . . . syn484N [H3N8, H4, H5, H6, H7N7, H9N2, H11])

. . . . TexasJMS380_2009_11_27 (
. . . . . . . . 25R,
. . . . . . . . syn53L [H2, H5N1 Viet Human, Avian, Civet, H6N1])

. . . . Tambov_SPN_2009_11_24_f (
. . . . . . . . syn6L [H3N8],
. . . . . . . . 19I [H3N8],
. . . . . . . . syn53L [H2, H5N1 Viet Human, Avian, Civet, H6N1],
. . . . . . . . syn177L [H3N8, H6, H7N7],
. . . . . . . . 225N,
. . . . . . . . 324I,
. . . . . . . . syn413K [H2, H5N1, H9N2],
. . . . . . . . syn542S [H2, H5, H9N2])

. . . . Ukraine123_2010_02_14_xL (
. . . . . . . . syn0T [BangkokINS427_27M_2010_03_04
. . . . . . . . . . . . . . . . . with syn209Y, syn232Y, syn490P & syn506V,
. . . . . . . . . . . . . DenmarkHvidovreINS290_20F_2009_11_27
. . . . . . . . . . . . . . . . . with 35I, syn490P, 502K & 526T,
. . . . . . . . . . . . . LaReunion3479_2009
. . . . . . . . . . . . . . . . . with syn97D, syn139C & 225E]
. . . . . . . . 186P,
. . . . . . . . 208K,
. . . . . . . . 230I (ATa),
. . . . . . . . syn238E [Ukraine122_2010_01_15_xL
. . . . . . . . . . . . . . . . . . . with 186P, 252M, 324I, syn413K,
. . . . . . . . . . . . . . . . . . . . . . syn431L & syn484N,
. . . . . . . . . . . . . . . WiscD2424_2009_12_15
. . . . . . . . . . . . . . . . . . . with 225E, 300S & 463T,
. . . . . . . . . . . . . . . Netherlands2629_2009_12_04_xL
. . . . . . . . . . . . . . . . . . . with 225N, syn233Y, 324I, syn413K & 507E,
. . . . . . . . . . . . . . . RussiaAnadyrIIV177_2009_12_04_xL_f
. . . . . . . . . . . . . . . . . . . with 225G, 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . JapanNagasakiHA64_2009_11_27
. . . . . . . . . . . . . . . . . . . with syn35L, syn92T, 200T, 324I & 513V,
. . . . . . . . . . . . . . . Arkhangelsk_GNY_2009_11_25_xL_f
. . . . . . . . . . . . . . . . . . . with 324I, syn413K, 437N & syn484N,
. . . . . . . . . . . . . . . MoscowCHSN_2009_11_23_xL_f
. . . . . . . . . . . . . . . . . . . with 225G, 324I & syn413K & syn484N,
. . . . . . . . . . . . . . . DenmarkHvidovreINS141_2009_11_20_xL
. . . . . . . . . . . . . . . . . . . with syn23L, 324I, syn413K, syn484N & syn549R,
. . . . . . . . . . . . . . . Lipetsk_BVV_2009_11_10_xL_f
. . . . . . . . . . . . . . . . . . . with 225G, 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . Orel_KAI1_2009_11_05
. . . . . . . . . . . . . . . . . . . with 280A, 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . Russia4_2009_11_01_xL
. . . . . . . . . . . . . . . . . . . with 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . Russia14_2009_11_01_xL
. . . . . . . . . . . . . . . . . . . with 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . Russia191_2009_11_01_xL
. . . . . . . . . . . . . . . . . . . with syn103E, 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . Belarus220_2009_11,
. . . . . . . . . . . . . . . Belarus360_2009_11,
. . . . . . . . . . . . . . . EgyptN14648_2009_11
. . . . . . . . . . . . . . . . . . . with 225N, 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . Belarus131_2009_10,
. . . . . . . . . . . . . . . GuamNHRC0032_2009_09_14
. . . . . . . . . . . . . . . . . . . with 89G,
. . . . . . . . . . . . . . . Managua5295_02_2009_07_23,
. . . . . . . . . . . . . . . ThailandTHA0364_2009_07_22
. . . . . . . . . . . . . . . . . . . with #12E, 37N, 296H & syn348V,
. . . . . . . . . . . . . . . Missouri02_2009_05_01
. . . . . . . . . . . . . . . . . . . with syn215P, syn377E, syn456L & syn523V,
. . . . . . . . . . . . . . . Bayern62S3_2009_04_29_VxX
. . . . . . . . . . . . . . . . . . . with 158E mix & syn238E,
. . . . . . . . . . . . . . . GermanyRegensburg01_2009_04_27
. . . . . . . . . . . . . . . . . . . with syn456L,
. . . . . . . . . . . . . . . GermanyRegensburgD6_2009
. . . . . . . . . . . . . . . . . . . with syn456L],
. . . . . . . . 252M [Fixed in 2010 Illinois swine with 119M,
. . . . . . . . . . . . . Ukraine122_2010_01_15_xL
. . . . . . . . . . . . . . . . . . . with 186P, 252M, 324I, syn413K,
. . . . . . . . . . . . . . . . . . . . . . syn431L & syn484N,
. . . . . . . . . . . . . Seoul2883_2009_12_02,
. . . . . . . . . . . . . Seoul1829_2009_11_26,
. . . . . . . . . . . . . LagosWRAIR1982N_2009_11_23,
. . . . . . . . . . . . . . . . . . . with syn164L, syn244T [u], syn291T,
. . . . . . . . . . . . . LagosWRAIR1984N_2009_11_18,
. . . . . . . . . . . . . . . . . . . with syn164L, syn244T [u], syn291T,
. . . . . . . . . . . . . LagosWRAIR1984T_2009_11_18
. . . . . . . . . . . . . . . . . . . with syn164L, syn244T [u], syn291T,
. . . . . . . . . . . . . UkrChernihiv857_2009_11_14_xL_f
. . . . . . . . . . . . . . . . . . . with 186P, 225G, syn238E, 324I,
. . . . . . . . . . . . . . . . . . . . . . . syn413K, syn431L, syn484N,
. . . . . . . . . . . . . Texas45132202_2009_09_13,
. . . . . . . . . . . . . Ancona86_2009_08_31
. . . . . . . . . . . . . . . . . . . with 225E & 300S,
. . . . . . . . . . . . . TurkeyAnkara17_2009_08,
. . . . . . . . . . . . . BZ_SaoPaulo43812_2009_07_03_f],
. . . . . . . . 289V [HK1881_2010_04_18,
. . . . . . . . . . . . . EstoniaTallinnINS431_2010_02_05,
. . . . . . . . . . . . . Luxembourg184_2010_01_25,
. . . . . . . . . . . . . Saarland21_2009_12_11,
. . . . . . . . . . . . . IndiaPune21115_2009_12 with 233H,
. . . . . . . . . . . . . Hiroshima457 _2009_11_02,
. . . . . . . . . . . . . JiangsuNanjinggulouSWL11146_2009_09_17,
. . . . . . . . . . . . . Kobe91993_2009_08_18,
. . . . . . . . . . . . . Kobe91992_2009_08_17,
. . . . . . . . . . . . . UK_Glascow_SC10_2009_06 with 225G,
. . . . . . . . . . . . . UK_Glascow_SC19_2009_06,
. . . . . . . . . . . . . UK_Glascow_SC20_2009_06],
. . . . . . . . 324I,
. . . . . . . . syn413K [H2, H5N1, H9N2],
. . . . . . . . syn431L [Emergent],
. . . . . . . . . . . . . . . [OZ_Grafton2_20F_2010_08_05
. . . . . . . . . . . . . . . . . . . . . . . with 128D, syn173G & syn273T,
. . . . . . . . . . . . . . . OZ_Perth504_5M_2010_07_07
. . . . . . . . . . . . . . . . . . . . . . . with 128D, syn173G & syn273T,
. . . . . . . . . . . . . . . swIllinois03037_2010_06_24
. . . . . . . . . . . . . . . . . . . . . . . with 77G,
. . . . . . . . . . . . . . . swIowa03032_2010_06_04
. . . . . . . . . . . . . . . . . . . . . . . with 77G,
. . . . . . . . . . . . . . . PNG_Goroka16_1F__2010_04_07
. . . . . . . . . . . . . . . . . . . . . . . with 77G & 252L,
. . . . . . . . . . . . . . . PNG_Goroka16E3_1F_2010_04_07
. . . . . . . . . . . . . . . . . . . . . . . with 77G, 186P, 204M, syn205G & 252L,
. . . . . . . . . . . . . . . PNG_Goroka15_2010_02_24
. . . . . . . . . . . . . . . . . . . . . . . with 77G & 252L,
. . . . . . . . . . . . . . . Ukraine122_2010_01_15_xL,
. . . . . . . . . . . . . . . HainanDinganSWL123_2010_01_08,
. . . . . . . . . . . . . . . swOregon10_004060_2009_12_31
. . . . . . . . . . . . . . . . . . . . . . . with syn189A,
. . . . . . . . . . . . . . . AthensINS359_2009_12_26
. . . . . . . . . . . . . . . . . . . . . . . with syn189A,
. . . . . . . . . . . . . . . UkrChernihiv857_2009_11_14_xL_f,
. . . . . . . . . . . . . . . SpainCatS1632_2009_10_28,
. . . . . . . . . . . . . . . swHongKong2314_2009_10_22,
. . . . . . . . . . . . . . . ItalyAncona05_2009_07-12
. . . . . . . . . . . . . . . . . . . . . . . with 225E,
. . . . . . . . . . . . . . . England673_2009_07
. . . . . . . . . . . . . . . . . . . . . . . with 225E],
. . . . . . . . syn484N [H3N8, H4, H5, H6, H7N7, H9N2, H11]),
. . . . . . . . . . . . . . . [NY04_2010_02_25
. . . . . . . . . . . . . . . . . . . with 3T, 50E, syn53L, 100N, syn232Y,
. . . . . . . . . . . . . . . . . . . . . . . syn270I, 377K, 437N,
. . . . . . . . . . . . . . . RussiaStPeter204E2E2_2010_02_08_VxX,
. . . . . . . . . . . . . . . RussiaStPeter204E2E1_2010_02_08_VxX,
. . . . . . . . . . . . . . . RussiaStPeter204E2_2010_02_08_VxX,
. . . . . . . . . . . . . . . Saratov07E2E1_2010_02_01_VxX,
. . . . . . . . . . . . . . . Saratov07E2_2010_02_01_VxX,
. . . . . . . . . . . . . . . Ukraine122_2010_01_15_xL
. . . . . . . . . . . . . . . . . . . with 186P, 252M, 324I, syn413K,
. . . . . . . . . . . . . . . . . . . . . . syn431L & syn484N,
. . . . . . . . . . . . . . . RussiaAnadyrIIV177_2009_12_04_xL_f
. . . . . . . . . . . . . . . . . . . with 225G, syn238E, 324I & syn413K,
. . . . . . . . . . . . . . . Arkhangelsk_GNY_2009_11_25_xL_f
. . . . . . . . . . . . . . . . . . . with 324I, syn413K, 437N & syn484N,
. . . . . . . . . . . . . . . MoscowCHSN_2009_11_23_xL_f
. . . . . . . . . . . . . . . . . . . with 225G, 324I & syn413K,
. . . . . . . . . . . . . . . DenmarkHvidovreINS141_2009_11_20_xL
. . . . . . . . . . . . . . . . . . . with syn23L, 324I, syn413K, syn484N & syn549R,
. . . . . . . . . . . . . . . RussiaStPeterVMN_2009_11_19_f,
. . . . . . . . . . . . . . . UkrChernihiv857_2009_11_14_xL_f
. . . . . . . . . . . . . . . . . . . with 186P, 225G, syn238E, 252M,
. . . . . . . . . . . . . . . . . . . . . . . 324I, syn413K, syn431L,
. . . . . . . . . . . . . . . UkrChernihiv855L_2009_11_11_xL_f,
. . . . . . . . . . . . . . . Lipetsk_BVV_2009_11_10_xL_f
. . . . . . . . . . . . . . . . . . . with 225G, 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . OrelKAI1_2009_11_05,
. . . . . . . . . . . . . . . Russia4_2009_11_01_xL,
. . . . . . . . . . . . . . . Russia14_2009_11_01_xL,
. . . . . . . . . . . . . . . Russia191_2009_11_01_xL,
. . . . . . . . . . . . . . . EgyptN14648_2009_11
. . . . . . . . . . . . . . . . . . . with 225N, syn238E, 324I & syn413K,
. . . . . . . . . . . . . . . RussiaStPeterRII96_2009_10_29
. . . . . . . . . . . . . . . . . . . with 187N,
. . . . . . . . . . . . . . . NizhniNovgorodMEV_2009_07_30,
. . . . . . . . . . . . . . . ItalyAncona15_2009_07_17,
. . . . . . . . . . . . . . . Fixed in Thai Swine including
. . . . . . . . . . . . . . . . . . . swThaiCU_RA75_2010_01 with 188T],
. . . . . . . . syn500R [Unique to GenBank/GISAID]),

. . . . Saratov07E2_24X_2010_02_01_xL_VxX (
. . . . . . . . 158E mix,
. . . . . . . . 225G,
. . . . . . . . syn235T [H3N8],
. . . . . . . . syn238E,
. . . . . . . . 324I,
. . . . . . . . syn413K [H2, H5N1, H9N2],
. . . . . . . . syn419L (CTt),
. . . . . . . . syn484N [H3N8, H4, H5, H6, H7N7, H9N2, H11])

. . . . Saratov07E2E1_24X_2010_02_01_ xL_VxX (
. . . . . . . . 47I mix,
. . . . . . . . 157E,
. . . . . . . . 158E mix,
. . . . . . . . 225G,
. . . . . . . . syn235T [H3N8],
. . . . . . . . syn238E,
. . . . . . . . 324I,
. . . . . . . . syn413K [H2, H5N1, H9N2],
. . . . . . . . syn419L (CTt),
. . . . . . . . syn484N [H3N8, H4, H5, H6, H7N7, H9N2, H11])

. . . . RussiaStPeter204E2_2010_02_08_ xL_VxX (
. . . . . . . . 157E,
. . . . . . . . 225G,
. . . . . . . . syn238E,
. . . . . . . . syn240G
. . . . . . . . 324I,
. . . . . . . . 275F,
. . . . . . . . syn413K [H2, H5N1, H9N2],
. . . . . . . . syn484N [H3N8, H4, H5, H6, H7N7, H9N2, H11])

. . . . AnadyrIIV177_2009_12_04_xL_f (
. . . . . . . . 212T [H3N8],
. . . . . . . . 225G,
. . . . . . . . syn238E [H2, H4],
. . . . . . . . 324I,
. . . . . . . . syn413K [H2, H5N1, H9N2],
. . . . . . . . syn484N [H3N8, H4, H5, H6, H7N7, H9N2, H11])

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October 2010 Sequences from Thailand Increase Genetic Diversity with 232H

The Mahidol University in Bangkok deposited a group of 6 pH1N1 HA sequences at GenBank on 2010-11-22. The samples were all taken last month, October 2010, and produced partial sequences.

ThaiSN_0116_2010_10 deploys a rare polymorphism at aa163 that may be related to our discussion of change at that position in April of this year.  Only New Zealand reports another instance of 163T.  Each 163T-bearing sequence is recent indicating potential emergent behaviour at this key amino acid position.  A second Thai sequence, ThaiSN_0112_2010_10, corroborates another novel amino acid revision (found only in Cuba).  232H, just downstream of the recent critical RBD revisions to 230I, increases the genetic diversity of the ΣPF11 reservoir.  The post-pandemic H1N1 virus appears to be as unstable as during the early pandemic.

Previously, we have detailed this genetic diversity and Vaccine Escape tendencies within this viral reservoir.  100% of the Hemagglutinin positions between 186 and 248, including antigenic areas of the Receptor Binding Domain (RBD/RBS), are on record as polymorphic.  No position in that range is stable.  Many positions rate multiple changes.   Protein revision is documented at 58 of the 63 positions (92%), engaging a wide potential for antibody resistance (natural Immune Escape and Vaccine Escape).

The related 232H-bearing Cuban sequence is from 2010 and mirrors directly and via domaining the emerging post-pandemic sub-clade recently profiled.

. . . . ThaiSN_0116_2010_10 (
. . . . . . . . HA truncated before aa119,
. . . . . . . . 163T [NZChristchurch16_2010_07_12],
. . . . . . . . syn177L,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . HA truncated after aa237)

. . . . ThaiSN_0112_2010_10 (
. . . . . . . . HA truncated before aa103,
. . . . . . . . 137T,
. . . . . . . . 186P,
. . . . . . . . 232H [CubaHabana7374_2010_01],
. . . . . . . . HA truncated after aa239)

Supporting Sequences

. . . . NZChristchurch16_2010_07_12 (
. . . . . . . . #4H,
. . . . . . . . syn44L,
. . . . . . . . 97N,
. . . . . . . . syn106E,
. . . . . . . . 128D,
. . . . . . . . 163T,
. . . . . . . . 225N,
. . . . . . . . 253A,
. . . . . . . . syn362S,
. . . . . . . . 377K)

. . . . CubaHabana7374_2010_01 (
. . . . . . . . HA truncated before aa05,
. . . . . . . . 28P,
. . . . . . . . syn32S,
. . . . . . . . 33G,
. . . . . . . . 165N,
. . . . . . . . 232H,
. . . . . . . . 275I,
. . . . . . . . syn287G,
. . . . . . . . syn305K,
. . . . . . . . syn346G,
. . . . . . . . 421M,
. . . . . . . . 432W,
. . . . . . . . 444Y,
. . . . . . . . HA truncated after aa535)

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HA 230I Demonstrated in Ukraine Cross-Linkage and in Russia with 225G

Last Updated
2011-02-09

The National Institute for Medical Research in the UK published a group of sequences on 2010-08-20 that included two instances of HA 230I from 2010 samples.  As predicted using GeneWurx RnR heuristics against the ΣPF11 reservoir (pH1N1), the Ukrainian reservoir and the Russian reservoir each now demonstrates support of the M230I polymorphism.  At this moment, this allegedly unpredictable disease has now been predicted in detail 3 times as to specific time, location and genetic change in addition to the original prediction of 230I emergence.

Previously, one military sequence from Texas, TexasAF2579_2009_10_04, was documented as the first 230I to meet the GeneWurx geographic prediction.  A dual RBD change (230I & 225E) is carried on the Texas sequence.  The Russian sequence detailed in this analysis is the first 230I with 225G, demonstrating multiple supports for dual RBD changes on these related backgrounds.

As early as November 2009 when less than 30 sequences with 225G had been published, our team discussed the high potential and variant mechanisms, including avian lateral transfer, for this pandemic to produce a recombinant with both 225G and 230I.  The change to 225G in pH1N1 has been associated with higher severity of disease and fatality potentially due to an increased ability to infect the ciliated cells of the respiratory system.  In effect, the 225G variants of Pandemic Influenza 2009 have a wider affinity for α2-3-linked sialic acid binding variety than the 1918 225G sample from New York.

The GeneWurx RnR model is now validated with predicted 230I data points within three geographic regions. The original emergence of 230I in the Pandemic H1N1 reservoir was accurately predicted using a model predating the RnR.  Furthermore, the M230I polymorphism count in this reservoir (H1N1pdm, pH1N1, PF11), increases to 8 at the same time that the H3N2 reservoir is building toward immune escape with an emerging sub-clade by revising at the same amino acid position (I230V).  Meanwhile, the Pandemic H1N1 reservoir is actively establishing an emergent sub-clade now crossing 9 distinct geographic regions, including the United States, Germany, South Africa and the Ukraine.  This emergent H1N1 sub-clade is permissive to 230I and 225G RBD changes.  One instance of this new pandemic H1N1 sub-clade is documented in Pennsylvania, a location where the H3N2 reservoir has begun the I230V revision.

A cursory contemporary analysis shows additional instances of H1N1 v. H3N2 reversals at similar positions or similar domains within particular geographic regions.  Will we find that the two serotypes (H1N1, H3N2) are in communication and are richly interactive?  Science has an unparalleled and unprecedented opportunity today to surveil, in real-time, a post-pandemic period.  Will deep surveillance and analysis be conducted or will the status quo be maintained, continuing with the same outdated models limited to the same inputs?

Age Factor and Mechanism Hypothesis

The 230I genetic modification appears to have a higher potential among children and young adults (0-24 years old).  The mechanism remains only in postulation due to sparsity of patient meta-data, treatment modality and clinical outcomes.  The pattern of revision on the known 230I sequences and on an emerging permissive background is suggestive that 230I is a tertiary immune escape polymorphism, whether developed in situ via a stepwise escape program or acquired via recombination from zoonotic sources.  Among individuals who have formed a wide, but only partially competent, series of antibodies, the longer viral infectious period due to incomplete clearance establishes the ideal incubation frame for a stepwise, hyper-morphic and/or novel viral revision.

Very generalised assays from various countries have reported pandemic virus exposure in their younger citizens at rates between 60% and 70%, seemingly a profound rate of protection or so-called herd immunity. However, the re-infection rates clarify that exposure does not equate to protection, though frequently the numbers are reported as protective due to assay titers results that have been deemed as “protective”. As the present evidence has demonstrated, the course of a pandemic viral disease is unaffected by the resulting outdated measures from these overly generalised assays that assume protection.

The younger group’s multiplicity of exposure to a wider variation of influenza strains may factor into the host response/viral revision equation.  Viral exertion against a complex host response challenges the reservoir subset to revise toward an optimal solution.  In short, for a virus to successfully replicate within a younger person today, increasing novelty may be required.  And this viral reservoir has demonstrated a very high capacity for continual novelty.

Additionally, studies have shown that anti-viral usage, specifically the neuraminidase inhibitors in wide usage, through the artificial mechanism of stalling the virus inside infected cells, may be involved in reducing the secondary immune response due to antigen sparsity and limiting the host ability to develop fully competent and protective antibodies. Given the Pandemic H1N1 reservoir’s demonstrated ability to hobble the early innate response (Natural Killer cells, Plasmocytoid Dendritic cells, et al) in combination with the NI anti-viral’s handicapping of the secondary (adaptive) response and the clinical outcomes are more explainable.

Ergo, take the wider exposure of the young population (antibody complexity/variety) and the TamiFlu blanketing used in schools and other institutions around the world (partial antibody competence) as synergistic factors toward a mechanism moulding the environment for 230I emergence as a tertiary immune escape revision.  Take the concern another step and consider the prospect of host latency due to viral-induced immune handicap . . . a simmering virus is a variable virus.  Furthermore, additional markers from fatalities and vaccine escape strains appear to be accumulating onto these 230I sequences and the sub-clades that are permissive to 230I.

Recall that a mature H5N1 strain in Gharbiyah, Egypt adapted to this same RBD revision under discussion here (230I) and increased the fatality rate substantially above worldwide baseline. Single genetic changes (SNP) are well-represented as fatality markers in this pandemic reservoir and in other zoonotic emergences.

230I Additions

The Institute of Epidemiology and Infectious Diseases AMS of Ukraine originated Ukraine123_2010_02_14_xL and the Russian Academy of Medical Sciences originated RussiaBelgorod2_2010_03_15.  Age and gender information remain undisclosed on each sequence of interest.

The hyper-morphic Ukraine123_2010_02_14_xL sequence carries 12 changes on the HA gene segment alone (6 silent).  This Ukrainian sample is the first instance of a cross-linked sequence with 230I and the first instantiation of a 230I-bearing strain carrying the 289V signature from India.  The synonymous 0T on the Ukrainian sequence is quite rare, but is found in two geographic locations that also demonstrate within their geographic pool the synonymous 238E found on the Ukrainian sequence: Thailand and Hvidovre.

. . . . Ukraine123_2010_02_14_xL (
. . . . . . . . syn0T [BangkokINS427_27M_2010_03_04
. . . . . . . . . . . . . . . . . with syn209Y, syn232Y, syn490P & syn506V,
. . . . . . . . . . . . . DenmarkHvidovreINS290_20F_2009_11_27
. . . . . . . . . . . . . . . . . with 35I, syn490P, 502K & 526T,
. . . . . . . . . . . . . LaReunion3479_2009
. . . . . . . . . . . . . . . . . with syn97D, syn139C & 225E]
. . . . . . . . 186P,
. . . . . . . . 208K,
. . . . . . . . 230I (ATa),
. . . . . . . . syn238E [Ukraine122_2010_01_15_xL
. . . . . . . . . . . . . . . . . . . with 186P, 252M, 324I, syn413K,
. . . . . . . . . . . . . . . . . . . . . . syn431L & syn484N,
. . . . . . . . . . . . . . . WiscD2424_2009_12_15
. . . . . . . . . . . . . . . . . . . with 225E, 300S & 463T,
. . . . . . . . . . . . . . . Netherlands2629_2009_12_04_xL
. . . . . . . . . . . . . . . . . . . with 225N, syn233Y, 324I, syn413K & 507E,
. . . . . . . . . . . . . . . RussiaAnadyrIIV177_2009_12_04_xL_f
. . . . . . . . . . . . . . . . . . . with 225G, 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . JapanNagasakiHA64_2009_11_27
. . . . . . . . . . . . . . . . . . . with syn35L, syn92T, 200T, 324I & 513V,
. . . . . . . . . . . . . . . Arkhangelsk_GNY_2009_11_25_xL_f
. . . . . . . . . . . . . . . . . . . with 324I, syn413K, 437N & syn484N,
. . . . . . . . . . . . . . . MoscowCHSN_2009_11_23_xL_f
. . . . . . . . . . . . . . . . . . . with 225G, 324I & syn413K & syn484N,
. . . . . . . . . . . . . . . DenmarkHvidovreINS141_2009_11_20_xL
. . . . . . . . . . . . . . . . . . . with syn23L, 324I, syn413K, syn484N & syn549R,
. . . . . . . . . . . . . . . Lipetsk_BVV_2009_11_10_xL_f
. . . . . . . . . . . . . . . . . . . with 225G, 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . Orel_KAI1_2009_11_05
. . . . . . . . . . . . . . . . . . . with 280A, 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . Russia4_2009_11_01_xL
. . . . . . . . . . . . . . . . . . . with 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . Russia14_2009_11_01_xL
. . . . . . . . . . . . . . . . . . . with 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . Russia191_2009_11_01_xL
. . . . . . . . . . . . . . . . . . . with syn103E, 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . Belarus220_2009_11,
. . . . . . . . . . . . . . . Belarus360_2009_11,
. . . . . . . . . . . . . . . EgyptN14648_2009_11
. . . . . . . . . . . . . . . . . . . with 225N, 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . Belarus131_2009_10,
. . . . . . . . . . . . . . . GuamNHRC0032_2009_09_14
. . . . . . . . . . . . . . . . . . . with 89G,
. . . . . . . . . . . . . . . Managua5295_02_2009_07_23,
. . . . . . . . . . . . . . . ThailandTHA0364_2009_07_22
. . . . . . . . . . . . . . . . . . . with #12E, 37N, 296H & syn348V,
. . . . . . . . . . . . . . . Missouri02_2009_05_01
. . . . . . . . . . . . . . . . . . . with syn215P, syn377E, syn456L & syn523V,
. . . . . . . . . . . . . . . Bayern62_2009_04_29_VxX
. . . . . . . . . . . . . . . . . . . with 158E & syn456L,
. . . . . . . . . . . . . . . GermanyRegensburg01_2009_04_27
. . . . . . . . . . . . . . . . . . . with syn456L,
. . . . . . . . . . . . . . . GermanyRegensburgD6_2009
. . . . . . . . . . . . . . . . . . . with syn456L],
. . . . . . . . 252M [Fixed in 2010 Illinois swine with 119M,
. . . . . . . . . . . . . Ukraine122_2010_01_15_xL
. . . . . . . . . . . . . . . . . . . with 186P, 252M, 324I, syn413K,
. . . . . . . . . . . . . . . . . . . . . . syn431L & syn484N,
. . . . . . . . . . . . . Seoul2883_2009_12_02,
. . . . . . . . . . . . . Seoul1829_2009_11_26,
. . . . . . . . . . . . . LagosWRAIR1982N_2009_11_23,
. . . . . . . . . . . . . . . . . . . with syn164L, syn244T [u], syn291T,
. . . . . . . . . . . . . LagosWRAIR1984N_2009_11_18,
. . . . . . . . . . . . . . . . . . . with syn164L, syn244T [u], syn291T,
. . . . . . . . . . . . . LagosWRAIR1984T_2009_11_18
. . . . . . . . . . . . . . . . . . . with syn164L, syn244T [u], syn291T,
. . . . . . . . . . . . . UkrChernihiv857_2009_11_14_xL_f
. . . . . . . . . . . . . . . . . . . with 186P, 225G, syn238E, 324I,
. . . . . . . . . . . . . . . . . . . . . . . syn413K, syn431L, syn484N,
. . . . . . . . . . . . . Texas45132202_2009_09_13,
. . . . . . . . . . . . . Ancona86_2009_08_31
. . . . . . . . . . . . . . . . . . . with 225E & 300S,
. . . . . . . . . . . . . TurkeyAnkara17_2009_08,
. . . . . . . . . . . . . BZ_SaoPaulo43812_2009_07_03_f],
. . . . . . . . 289V [HK1881_2010_04_18,
. . . . . . . . . . . . . EstoniaTallinnINS431_2010_02_05,
. . . . . . . . . . . . . Luxembourg184_2010_01_25,
. . . . . . . . . . . . . Saarland21_2009_12_11,
. . . . . . . . . . . . . IndiaPune21115_2009_12 with 233H,
. . . . . . . . . . . . . Hiroshima457 _2009_11_02,
. . . . . . . . . . . . . JiangsuNanjinggulouSWL11146_2009_09_17,
. . . . . . . . . . . . . Kobe91993_2009_08_18,
. . . . . . . . . . . . . Kobe91992_2009_08_17,
. . . . . . . . . . . . . UK_Glascow_SC10_2009_06 with 225G,
. . . . . . . . . . . . . UK_Glascow_SC19_2009_06,
. . . . . . . . . . . . . UK_Glascow_SC20_2009_06],
. . . . . . . . 324I,
. . . . . . . . syn413K,
. . . . . . . . syn431L [Emergent],
. . . . . . . . . . . . . . . [OZ_Grafton2_20F_2010_08_05
. . . . . . . . . . . . . . . . . . . . . . . with 128D, syn173G & syn273T,
. . . . . . . . . . . . . . . OZ_Perth504_5M_2010_07_07
. . . . . . . . . . . . . . . . . . . . . . . with 128D, syn173G & syn273T,
. . . . . . . . . . . . . . . swIllinois03037_2010_06_24
. . . . . . . . . . . . . . . . . . . . . . . with 77G,
. . . . . . . . . . . . . . . swIowa03032_2010_06_04
. . . . . . . . . . . . . . . . . . . . . . . with 77G,
. . . . . . . . . . . . . . . PNG_Goroka16_1F__2010_04_07
. . . . . . . . . . . . . . . . . . . . . . . with 77G & 252L,
. . . . . . . . . . . . . . . PNG_Goroka16E3_1F_2010_04_07
. . . . . . . . . . . . . . . . . . . . . . . with 77G, 186P, 204M, syn205G & 252L,
. . . . . . . . . . . . . . . PNG_Goroka15_2010_02_24
. . . . . . . . . . . . . . . . . . . . . . . with 77G & 252L,
. . . . . . . . . . . . . . . Ukraine122_2010_01_15_xL,
. . . . . . . . . . . . . . . HainanDinganSWL123_2010_01_08,
. . . . . . . . . . . . . . . swOregon10_004060_2009_12_31
. . . . . . . . . . . . . . . . . . . . . . . with syn189A,
. . . . . . . . . . . . . . . AthensINS359_2009_12_26
. . . . . . . . . . . . . . . . . . . . . . . with syn189A,
. . . . . . . . . . . . . . . UkrChernihiv857_2009_11_14_xL_f,
. . . . . . . . . . . . . . . SpainCatS1632_2009_10_28,
. . . . . . . . . . . . . . . swHongKong2314_2009_10_22,
. . . . . . . . . . . . . . . ItalyAncona05_2009_07-12
. . . . . . . . . . . . . . . . . . . . . . . with 225E,
. . . . . . . . . . . . . . . England673_2009_07
. . . . . . . . . . . . . . . . . . . . . . . with 225E],
. . . . . . . . syn484N [H3N8, H4, H5, H6, H7N7, H9N2, H11]),
. . . . . . . . . . . . . . . [NY04_2010_02_25
. . . . . . . . . . . . . . . . . . . with 3T, 50E, syn53L, 100N, syn232Y,
. . . . . . . . . . . . . . . . . . . . . . . syn270I, 377K, 437N,
. . . . . . . . . . . . . . . RussiaStPeter204E2E2_2010_02_08_VxX,
. . . . . . . . . . . . . . . RussiaStPeter204E2E1_2010_02_08_VxX,
. . . . . . . . . . . . . . . RussiaStPeter204E2_2010_02_08_VxX,
. . . . . . . . . . . . . . . Saratov07E2E1_2010_02_01_VxX,
. . . . . . . . . . . . . . . Saratov07E2_2010_02_01_VxX,
. . . . . . . . . . . . . . . Ukraine122_2010_01_15_xL
. . . . . . . . . . . . . . . . . . . with 186P, 252M, 324I, syn413K,
. . . . . . . . . . . . . . . . . . . . . . syn431L & syn484N,
. . . . . . . . . . . . . . . RussiaAnadyrIIV177_2009_12_04_xL_f
. . . . . . . . . . . . . . . . . . . with 225G, syn238E, 324I & syn413K,
. . . . . . . . . . . . . . . Arkhangelsk_GNY_2009_11_25_xL_f
. . . . . . . . . . . . . . . . . . . with 324I, syn413K, 437N & syn484N,
. . . . . . . . . . . . . . . MoscowCHSN_2009_11_23_xL_f
. . . . . . . . . . . . . . . . . . . with 225G, 324I & syn413K,
. . . . . . . . . . . . . . . DenmarkHvidovreINS141_2009_11_20_xL
. . . . . . . . . . . . . . . . . . . with syn23L, 324I, syn413K, syn484N & syn549R,
. . . . . . . . . . . . . . . RussiaStPeterVMN_2009_11_19_f,
. . . . . . . . . . . . . . . UkrChernihiv857_2009_11_14_xL_f
. . . . . . . . . . . . . . . . . . . with 186P, 225G, syn238E, 252M,
. . . . . . . . . . . . . . . . . . . . . . . 324I, syn413K, syn431L,
. . . . . . . . . . . . . . . UkrChernihiv855L_2009_11_11_xL_f,
. . . . . . . . . . . . . . . Lipetsk_BVV_2009_11_10_xL_f
. . . . . . . . . . . . . . . . . . . with 225G, 324I, syn413K & syn484N,
. . . . . . . . . . . . . . . OrelKAI1_2009_11_05,
. . . . . . . . . . . . . . . Russia4_2009_11_01_xL,
. . . . . . . . . . . . . . . Russia14_2009_11_01_xL,
. . . . . . . . . . . . . . . Russia191_2009_11_01_xL,
. . . . . . . . . . . . . . . EgyptN14648_2009_11
. . . . . . . . . . . . . . . . . . . with 225N, syn238E, 324I & syn413K,
. . . . . . . . . . . . . . . RussiaStPeterRII96_2009_10_29
. . . . . . . . . . . . . . . . . . . with 187N,
. . . . . . . . . . . . . . . NizhniNovgorodMEV_2009_07_30,
. . . . . . . . . . . . . . . ItalyAncona15_2009_07_17,
. . . . . . . . . . . . . . . Fixed in Thai Swine including
. . . . . . . . . . . . . . . . . . . swThaiCU_RA75_2010_01 with 188T],
. . . . . . . . syn500R [Unique to GenBank/GISAID])

. . . . RussiaBelgorod2_2010_03_15 (
. . . . . . . . syn13N [WiscD0459_2009_12_18_xL
. . . . . . . . . . . . . . . . . . with 189T, 324I & 499K,
. . . . . . . . . . . . . . LouisianaAF2435_2009_11_30
. . . . . . . . . . . . . . . . . . with syn338G],
. . . . . . . . 77N [tn, swine, S5]
. . . . . . . . . . . [JapanOsaka60_2010_07_02
. . . . . . . . . . . . . . . . with syn276H,
. . . . . . . . . . . Maryland04_2010_02_08
. . . . . . . . . . . . . . . . with syn276H,
. . . . . . . . . . . ShandongShizhongSWL24_2010_01_24,
. . . . . . . . . . . NY7020_2009_12_14
. . . . . . . . . . . . . . . . with syn166K & 189T,
. . . . . . . . . . . CalifVRDL115_2009_12_04
. . . . . . . . . . . . . . . . with syn276H,
. . . . . . . . . . . JapanAF2267_2009_11_09
. . . . . . . . . . . . . . . . with 286E,
. . . . . . . . . . . NevadaAF2490_2009_11_02
. . . . . . . . . . . . . . . . with 100N & syn270I,
. . . . . . . . . . . AlaskaAF2093_2009_11_02
. . . . . . . . . . . . . . . . with 286E,
. . . . . . . . . . . Russia74_2009_11_01_xL,
. . . . . . . . . . . ThailandTHB0441_2009_07_28,
. . . . . . . . . . . Lisboa40_2009_06_23,
. . . . . . . . . . . AnhuiSWL1_2009_06_18
. . . . . . . . . . . . . . . . with 275I,
. . . . . . . . . . . Lithuania1942_2009,
. . . . . . . . . . . swKoreaSCJ10_2009_12,
. . . . . . . . . . . swKoreaSCJ09_2009_12]
. . . . . . . . 158E mix,
. . . . . . . . 225G (Gga) stepwise from 225E,
. . . . . . . . 230I (ATa),
. . . . . . . . 238D [H2N3, H7N3, H7N7, tn, swine],
. . . . . . . . . . . . [PNG_Goroka17_2010_04_14,
. . . . . . . . . . . . AthensINS398_2010_01_24,
. . . . . . . . . . . . AthensINS339_2009_12_30,
. . . . . . . . . . . . Kaliningrad01_11M_2009_11_02
. . . . . . . . . . . . . . . . . . with 225E & 226R,
. . . . . . . . . . . . KaliningradCRIE_DA_2009_09_26,
. . . . . . . . . . . . KaliningradCRIE_KG_2009_09_25,
. . . . . . . . . . . . KaliningradCRIE_SHD_2009_09_25,
. . . . . . . . . . . . KaliningradCRIE_MA_2009_09_25,
. . . . . . . . . . . . KaliningradCRIE_ZD_2009_09_25],
. . . . . . . . syn245F [H2N3, H5N1, H7N7, H10N7, H11]
. . . . . . . . . . . . . . [SingON2416_2009_12_15
. . . . . . . . . . . . . . . . . . . . . with syn166K & 300P,
. . . . . . . . . . . . . . . EgyptAswan2288_2009_11_02
. . . . . . . . . . . . . . . . . . . . . with 189T],
. . . . . . . . 300S [H7N3, H7N7 (tCt)],
. . . . . . . . 305N (AAc) [ThaiChiangRai226_2M_2010_03_04
. . . . . . . . . . . . . . . . . . . . . . . with 270T,
. . . . . . . . . . . . . . . . . . Brunei5_52M_2010,
. . . . . . . . . . . . . . . . . . SouthCarolinaAF2562_2009_11_15 (AAt),
. . . . . . . . . . . . . . . . . . DenmarkAalborgINS133_2009_12_02 (AAt)],
. . . . . . . . syn343G [H3N8, H5N1, H6N1, H7N3, H7N7, H10N7, H11, 1918],
. . . . . . . . . . . . . . . [Thuringen189_2009_11_24_xL,
. . . . . . . . . . . . . . . Thuringen227_11_17_xL])

Prediction

• 2010-09-26 HA 230I RBS Polymorphism Potential for Pennsylvania
• 2010-08-31 HA 230I RBS Polymorphism Potential for Europe
• 2010-08-09 HA 230I Receptor Binding Domain Polymorphism Potential for Spread
• 2010-02-25 HA 230I Receptor Binding Domain Polymorphism Probable for PF11
• 2009-11-20 225G New to Norway and Ukraine; Worldwide Evaluation Concerning Range and Co-Circulation with 225E

Prediction Validation

• 2010-08-27 HA 230I Documented in Texas with 225E RBD Revision
• 2010-05-10 pH1N1 Surpasses 95% Instability In Critical Genetics Range with Extensive Bird Flu Inclusions
• 2010-05-05 90% Change Rate on Unstable HA Antigen Range with H9N2 and H5N1 Bird Flu Matches
• 2010-03-31 Zoonotic H9N2 Avian Influenza Further Destabilises H1N1 Pandemic Genetics

Supporting Sequences

. . . . Fukuoka_C34_2010_04_09 (
. . . . . . . . syn#12K,
. . . . . . . . 22I,
. . . . . . . . syn103E,
. . . . . . . . 115K,
. . . . . . . . 165N,
. . . . . . . . 230I (ATa),
. . . . . . . . 274S [Iowa14_2009_12_07
. . . . . . . . . . . . . . . . with 119M],
. . . . . . . . HA truncated after aa329)

. . . . Minnesota04_18M_2010_03_22 (
. . . . . . . . 34D,
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F,
. . . . . . . . 218V,
. . . . . . . . 230I (ATa),
. . . . . . . . syn305K,
. . . . . . . . 313I [Orenburg2974_2009_11_16_xL
. . . . . . . . . . . . . . . . with 225N],
. . . . . . . . syn346G)

. . . . Wisc0337_09M_2009_12_15 (
. . . . . . . . 230I (ATa),
. . . . . . . . 275A,
. . . . . . . . 377K [H9N2])

. . . . TexasAF2579_18M_2009_10_04 (
. . . . . . . . syn20D,
. . . . . . . . 225E,
. . . . . . . . 230I (ATa),
. . . . . . . . syn246E,
. . . . . . . . 264D,
. . . . . . . . 300S,
. . . . . . . . HA truncated after aa386)

. . . . Guangdong2282_20M_2009_11_23 (
. . . . . . . . 131P,
. . . . . . . . 202A,
. . . . . . . . 230I (ATt),
. . . . . . . . 244I,
. . . . . . . . 275A)

. . . . LiaoningShuncheng1148_17F _2009_10_14 (
. . . . . . . . 131P,
. . . . . . . . 202A,
. . . . . . . . 230I (ATt),
. . . . . . . . 244I,
. . . . . . . . 275A)

Related Sequences

. . . . RussiaAnadyrIIV177_2009_12_04_xL_f (
. . . . . . . . 212T [H3N8],
. . . . . . . . 225G,
. . . . . . . . syn238E [H2, H4],
. . . . . . . . 324I,
. . . . . . . . syn413K [H9N2],
. . . . . . . . syn484N [H3N8, H4, H5, H6, H7N7, H9N2, H11])

. . . . Moscow_CHSN_2009_11_23_xL_f (
. . . . . . . . syn177L [H3N8, H6, H7N7],
. . . . . . . . 225G,
. . . . . . . . 324I,
. . . . . . . . syn376D [H2, H3N8, H4, H5, H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . syn413K [H2, H5N1, H9N2],
. . . . . . . . syn484N [H3N8, H4, H5N1 (E/A/H), H6, H7N7, H9N2, H11]),
. . . . . . . . syn542S [H2, H5N1, H9N2])

. . . . Lipetsk_BVV_2009_11_10_xL_f (
. . . . . . . . syn177L [H3N8, H6, H7N7],
. . . . . . . . 225G mix,
. . . . . . . . syn238E [H2, H4],
. . . . . . . . syn240G [H3N8, H6, H9N2, H11],
. . . . . . . . 324I,
. . . . . . . . syn413K [H2, H5N1, H9N2],
. . . . . . . . syn542S [H2, H5N1, H9N2])

. . . . Arkhangelsk_GNY_2009_11_25_xL_f (
. . . . . . . . syn134G [H2, H3N8, H4, H5N1 (E/A/H), H6, H9N2, H11],
. . . . . . . . syn177L [H3N8, H6, H7N7],
. . . . . . . . syn238E [H2, H4],
. . . . . . . . syn240G [H3N8, H6, H9N2, H11],
. . . . . . . . 324I,
. . . . . . . . syn413K [H2, H5N1, H9N2],
. . . . . . . . 437N,
. . . . . . . . syn484N [H3N8, H4, H5N1 (E/A/H), H6, H7N7, H9N2, H11])

. . . . Orel_KAI1_2009_11_05 (
. . . . . . . . syn238E,
. . . . . . . . 280A,
. . . . . . . . 324I,
. . . . . . . . syn406R,
. . . . . . . . syn413K,
. . . . . . . . syn484N,
. . . . . . . . syn542S)

. . . . Saratov07E2E1_2010_02_01_ xL_VxX (
. . . . . . . . 46I mix,
. . . . . . . . 157E,
. . . . . . . . 158E mix,
. . . . . . . . 225G,
. . . . . . . . syn235T,
. . . . . . . . syn238E,
. . . . . . . . 324I,
. . . . . . . . syn413K [H2, H5N1, H9N2],
. . . . . . . . syn419L (CTt),
. . . . . . . . syn484N),

. . . . StPeter_VMN_2009_11_19_f (
. . . . . . . . syn202V,
. . . . . . . . syn238E,
. . . . . . . . syn240G,
. . . . . . . . 275F,
. . . . . . . . 324I,
. . . . . . . . syn413K,
. . . . . . . . syn484N,
. . . . . . . . syn542S [H2, H5, H9N2])

. . . . RussiaStPeter204E2_2010_02_08_ xL_VxX (
. . . . . . . . 157E,
. . . . . . . . 225G,
. . . . . . . . syn238E,
. . . . . . . . syn240G
. . . . . . . . 324I,
. . . . . . . . 275F,
. . . . . . . . syn413K [H2, H5N1, H9N2],
. . . . . . . . syn484N),

. . . . Netherlands2629_2009_12_04_xL (
. . . . . . . . syn58C [H2N3, H3N8, H4, H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . 225N,
. . . . . . . . syn233Y,
. . . . . . . . syn238E,
. . . . . . . . 324I,
. . . . . . . . 377K [H9N2],
. . . . . . . . syn413K [H9N2],
. . . . . . . . 507E),

. . . . EgyptN14648_2009_11 (
. . . . . . . . 225N,
. . . . . . . . syn238E,
. . . . . . . . 285S,
. . . . . . . . 324I,
. . . . . . . . syn413K,
. . . . . . . . syn484N [H3N8, H4, H5, H6, H7N7, H9N2, H11])

. . . . RussiaStPeterRII96_2009_10_29 (
. . . . . . . . syn23L,
. . . . . . . . syn91G,
. . . . . . . . syn166K,
. . . . . . . . 187N,
. . . . . . . . syn305K,
. . . . . . . . syn484N)

. . . . UkrChernihiv857_2009_11_14_xL_f (
. . . . . . . . 186P,
. . . . . . . . 225G mix wt,
. . . . . . . . syn238E,
. . . . . . . . 252M,
. . . . . . . . 324I,
. . . . . . . . syn413K,
. . . . . . . . syn431L,
. . . . . . . . syn484N)

. . . . Ukraine122_2010_01_15_xL (
. . . . . . . . 20Y,
. . . . . . . . 186P,
. . . . . . . . syn238E,
. . . . . . . . 252M,
. . . . . . . . 324I,
. . . . . . . . syn413K,
. . . . . . . . syn431L,
. . . . . . . . syn484N)

. . . . Ukraine221_2009_11_02_xL (
. . . . . . . . syn213F,
. . . . . . . . 324I,
. . . . . . . . syn413K)

. . . . Ukraine229_2009_12_25 (
. . . . . . . . syn19V,
. . . . . . . . syn213F,
. . . . . . . . syn346G,
. . . . . . . . 377K)

. . . . DenmarkHvidovreINS141_2009_11_20_xL (
. . . . . . . . syn23L,
. . . . . . . . syn238E,
. . . . . . . . 324I,
. . . . . . . . syn413K,
. . . . . . . . syn484N,
. . . . . . . . syn549R)

. . . . DenmarkAalborgINS133_2009_12_02 (
. . . . . . . . 305N (AAt) [SouthCarolinaAF2562_2009_11_15
. . . . . . . . . . . . . . . . . . RussiaBelgorod2_2010_03_15 (AAc)],
. . . . . . . . 377K,
. . . . . . . . syn472H,
. . . . . . . . 530I)

. . . . LouisianaAF2435_2009_11_30 (
. . . . . . . . syn13N,
. . . . . . . . syn256Y,
. . . . . . . . syn283Q,
. . . . . . . . syn338G,
. . . . . . . . syn339F,
. . . . . . . . 377K,
. . . . . . . . HA truncated after aa386)

. . . . WiscD0459_2009_12_18_xL (
. . . . . . . . syn13N,
. . . . . . . . syn32S,
. . . . . . . . 189T,
. . . . . . . . 324I,
. . . . . . . . syn413K,
. . . . . . . . syn474C,
. . . . . . . . 499K)

. . . . WiscD2424_2009_12_15 (
. . . . . . . . syn119I,
. . . . . . . . syn121P,
. . . . . . . . syn132N,
. . . . . . . . 225E,
. . . . . . . . syn238E,
. . . . . . . . 300S,
. . . . . . . . 463T)

. . . . SouthCarolinaAF2562_2009_11_15 (
. . . . . . . . syn177L (CTt),
. . . . . . . . 305N (AAt) [DenmarkAalborgINS133_2009_12_02,
. . . . . . . . . . . . . . . . . . RussiaBelgorod2_2010_03_15 (AAc)],
. . . . . . . . HA truncated after aa386)

. . . . Georgia4032_2009_12_09 (
. . . . . . . . syn27V,
. . . . . . . . syn71E [Moscow, Ivanovo graphic],
. . . . . . . . syn158G,
. . . . . . . . syn213F,
. . . . . . . . 214R,
. . . . . . . . 225E,
. . . . . . . . syn276H,
. . . . . . . . syn321L [MXinDRE797 2010 TmX,
. . . . . . . . . . . . . . . UkrSumy795_2009_11_13_f ,
. . . . . . . . . . . . . . . UkrRivne596_2009_11_12_f],
. . . . . . . . 377K)

. . . . NevadaAF2490_2009_11_02 (
. . . . . . . . 77N,
. . . . . . . . 100N,
. . . . . . . . syn270I,
. . . . . . . . 377K,
. . . . . . . . HA truncated after aa386)

. . . . Maryland04_2010_02_08
. . . . . . . . 35I,
. . . . . . . . 77N,
. . . . . . . . 88T,
. . . . . . . . syn152I,
. . . . . . . . 206S,
. . . . . . . . syn219I,
. . . . . . . . syn276H,
. . . . . . . . syn456L,
. . . . . . . . 463V,
. . . . . . . . 523A)

. . . . NY7020_2009_12_14 (
. . . . . . . . 77N,
. . . . . . . . syn166K,
. . . . . . . . 189T,
. . . . . . . . 377K)

. . . . FL_PenINS213_2009_11_17 (
. . . . . . . . . . . . 35I [H5N1],
. . . . . . . . . . . . syn152I,
. . . . . . . . . . . . syn219I,
. . . . . . . . . . . . 273A,
. . . . . . . . . . . . syn276H [1918, S5],
. . . . . . . . . . . . syn456L [H5N1],
. . . . . . . . . . . . 463V,
. . . . . . . . . . . . 523A)

. . . . CalifVRDL107_2009_11_15 (
. . . . . . . . . . . . 35I [H5N1],
. . . . . . . . . . . . 39N,
. . . . . . . . . . . . syn152I,
. . . . . . . . . . . . syn219I,
. . . . . . . . . . . . syn276H [1918, S5],
. . . . . . . . . . . . syn456L [H5N1],
. . . . . . . . . . . . 463V,
. . . . . . . . . . . . 523A)

. . . . CalifVRDL115_2009_12_04 (
. . . . . . . . . . . . 35I [H5N1],
. . . . . . . . . . . . 77N [NY7020_2009_12_14 with 189T],
. . . . . . . . . . . . syn152I,
. . . . . . . . . . . . syn219I,
. . . . . . . . . . . . syn276H [1918, S5],
. . . . . . . . . . . . syn456L [H5N1],
. . . . . . . . . . . . 463V,
. . . . . . . . . . . . 523A),

. . . . HongKong1881_2010_04_18 (
. . . . ~ FL_PenINS213_2009_11_17 with Ukraine and India additions
. . . . . . . . syn2N [SingON2416_2009_12_15,
. . . . . . . . . . . . . UkrSumy797_2009_11_13_f,
. . . . . . . . . . . . . UkrLviv673_2009_11_09_xL,
. . . . . . . . . . . . . UkrLviv673S2_2009_11_09,
. . . . . . . . . . . . . MongoliaJP5756_2009_10_15,
. . . . . . . . . . . . . UkrLvivN2_2009_10_28_xL_f,
. . . . . . . . . . . . . IndiaPune10604_2009_09,
. . . . . . . . . . . . . IndiaPune6196_2009_08,
. . . . . . . . . . . . . IndiaDhule9433_2009_08,
. . . . . . . . . . . . . IndiaPune807_2009_07],
. . . . . . . . 35I,
. . . . . . . . syn152I,
. . . . . . . . 206S,
. . . . . . . . syn219I,
. . . . . . . . syn254P,
. . . . . . . . syn276H,
. . . . . . . . 289V,
. . . . . . . . syn456L,
. . . . . . . . 463V,
. . . . . . . . 523A)

. . . . GhanaFS1940_2009_11_13 (
. . . . . . . . syn139C,
. . . . . . . . syn213F,
. . . . . . . . syn228G,
. . . . . . . . 261K,
. . . . . . . . 296H,
. . . . . . . . syn346G,
. . . . . . . . syn404E)

. . . . GhanaFS09_1181_2009_08_07 (
. . . . . . . . syn213F,
. . . . . . . . 380D mix wt [Unique to GISAID])

. . . . EgyptAswan2288_2009_11_02 (
. . . . . . . . 189T,
. . . . . . . . syn245F,
. . . . . . . . 377K [H9N2]),

. . . . JapanOsaka60_2010_07_02 (
. . . . . . . . 35I,
. . . . . . . . 77N,
. . . . . . . . 115K,
. . . . . . . . syn152I,
. . . . . . . . 206S,
. . . . . . . . syn214K,
. . . . . . . . syn219I,
. . . . . . . . syn254P,
. . . . . . . . syn276H,
. . . . . . . . HA truncated after aa330)

. . . . JapanNagasakiHA64_2009_11_27 (
. . . . . . . . syn35L,
. . . . . . . . syn92T,
. . . . . . . . syn136T,
. . . . . . . . 200T,
. . . . . . . . syn238E,
. . . . . . . . 324I,
. . . . . . . . 513V),

. . . . ShandongShizhongSWL24_2010_01_24 (
. . . . . . . . HA truncated until aa23,
. . . . . . . . 24A,
. . . . . . . . 25M,
. . . . . . . . 77N,
. . . . . . . . 131P,
. . . . . . . . syn439D,
. . . . . . . . HA truncated after aa526)

. . . . AnhuiSWL1_2009_06_18 (
. . . . . . . . 77N,
. . . . . . . . 206S,
. . . . . . . . 275I,
. . . . . . . . syn397G)

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