UK and Iran Transmit Hyper-Zoonotic Genetics in Late 2010

The Tehran University of Medical Sciences has made available 3 sets of sequences at GenBank recently that were sampled on 2010_10_02 with 2 additional divergent samples taken on 2010-12-06.  These sequences directly parallel the developments from the UK Severe Wave and additionally feature hyper-zoonotic, sub-segment HA genetic acquisition.

Though considerable divergency is currently being demonstrated within the recent UK severe wave, two different sets of combinations have been coalescing throughout the world since late 2009 and have begun forming sub-clades in the past 4 months that are demonstrated well in these 3 Iranian sequences.

Do these Iranian sequences signal the type of zoonotic genetic behaviour that is driving some areas of the UK today to report an 800% rise in the number ill from Pandemic H1N1?

Though the origins of the primary branching polymorphisms begin much earlier, the later stages of transmission during late Summer and early Fall 2010 (Northern Hemisphere designations) more clearly distinguish the coalescence.  Florida13 and Florida14 during August 2010 are recorded as having progenitor co-circulation of these two divergent sub-clades that transmitted and continued into the UK and Iran.  Florida13_2010_08_02 has 4 of the same SNPs as IranBandarAbbas5096_2010_10_02. 100% of those matches [4 of 4 (137T, 186P, 377G, syn474C)] between Florida and Iran are also found in animal reservoirs.

Recall that small incursions of genetics from animal reservoirs are known to imbalance viral behaviour in the new human host. The HA 377G found on Florida13 and BandarAbbas5096 exists on the fatal UKEngland4500186_2010_11_f sequence and four other UK sequences from October and November of 2010, but was not notated on the HPA Ellis Figure3 ¹ phylogenetic tree.

• UKEngland83_2010_10
• UKEngland87_2010_10
• UKEngland5500192_2010_10
• UKEngland119_2010_11
• UKEngland4500186_2010_11_f

GeneWurx has annotated the Ellis Figure3 ¹ phylogenetic tree with green boxes next to the four fatal GISAID 2010-12-20 deposited sequences and has proposed polymorphism notations including the zoonotic HA 377G on various unmarked branches in an attempt to provide clarity.  Version 5 of the Emerging Genetics spreadsheet is available with the Iranian sequences, the 4 representative UK 377G sequences (UKEngland5500192_2010_10 is identical to UKEngland87_2010_10) and the majority of the released UK fatalities.

• UK_2010_Phylo_ELLIS_Fig3new_4_GISAID_Notated_2011_01_13.JPG
• GeneWurx_UK_December_Emerging_Genetics_v5.xls

The IranShahriar5336_2010_12_06 evaluation details a remarkable hyper-zoonosis. At least 78% of the polymorphisms (7 of 9) are clearly demonstrated as amino acid variation or single nucleotide polymorphisms in animal reservoirs, primarily H3N8, H5N1 and H7N7. Wisconsin08_2010_08_10 shares homology at 7 of the IranShahriar5336_2010_12_06 SNPs.  86% of those matches [6 of 7 (137T, 186P, syn297N, 388K, 444K, syn474C)] between Wisconsin and Iran are found in animals (5 in H3N8).

The homology between Iran and the UK is more striking than either of these vivid US examples and may be well visualised by scrolling through the GeneWurx v5 spreadsheet detailing these specific changes with combinational development over the course of this pandemic.

. . . . IranShahriar5336_2010_12_06 (
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . syn297N [H3N8 gadwallRussiaAltai1325_2007_09],
. . . . . . . . . . . . . . . [H5N1],
. . . . . . . . . . . . . . . [Wisconsin08_2010_08_10
. . . . . . . . . . . . . . . . . . . . . . with 39R, syn78S, 137T, 186P, syn297N,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn326S, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn413K, 444K, syn474C,
. . . . . . . . . . . . . . . CalifVRDL2_2010_01_11
. . . . . . . . . . . . . . . . . . . . . . with syn121P & 502K,
. . . . . . . . . . . . . . . YaroslavlIIV196_2009_12_04_f
. . . . . . . . . . . . . . . . . . . . . . with syn159N, 225G,
. . . . . . . . . . . . . . . WiscD0128_2009_11_15
. . . . . . . . . . . . . . . . . . . . . . with syn343G, 377G, 471H,
. . . . . . . . . . . . . . . Brussels243_2009_11_09
. . . . . . . . . . . . . . . . . . . . . . with syn44L, syn159N & syn323N,
. . . . . . . . . . . . . . . Australia6_2009_07_18
. . . . . . . . . . . . . . . . . . . . . . with syn159N, 233H]
. . . . . . . . syn326S [Wisconsin08_2010_08_10
. . . . . . . . . . . . . . . . . . . . . . with 39R, syn78S, 137T, 186P, syn297N,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn326S, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn413K, 444K, syn474C,
. . . . . . . . . . . . . . . Zhongyuan1643_2009_11_16
. . . . . . . . . . . . . . . . . . . . . . with 208G],
. . . . . . . . syn383N [H3N8],
. . . . . . . . syn388K [H3N8, H5N1, S7],
. . . . . . . . . . . . . . . [OzVictoria508_2010_07_24
. . . . . . . . . . . . . . . . . . . . . . . with 238D,
. . . . . . . . . . . . . . . swIowa44837_1_2009_11_08_xL
. . . . . . . . . . . . . . . . . . . . . . . with 188R, 225N & 230I,
. . . . . . . . . . . . . . . Utah20_C2_2_2009_07_25_VxX
. . . . . . . . . . . . . . . . . . . . . . . with 159D & 227G, et al],
. . . . . . . . syn411N (AAc) [H7N3 & H7N7 donor ATc],
. . . . . . . . 444K (AAg) [H3N8 gAg],
. . . . . . . . syn474C [H3N8, Avian H1N1 2010],
. . . . . . . . . . . . . . . [Michigan10_2009_06_03 with 137T, 225N, et al])

. . . . IranBandarAbbas5096_2010_10_02 (
. . . . . . . . 72P,
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . syn318A,
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . . . . . . [Florida13_2010_08_02
. . . . . . . . . . . . . . . . . . . with 137T, 186P, syn474C, 512M,
. . . . . . . . . . . . . . Iowa05_2010_05_04
. . . . . . . . . . . . . . . . . . . with 208K, syn516I,
. . . . . . . . . . . . . . swSouthDakota1_2010_04_27,
. . . . . . . . . . . . . . TexasAF2647_2010_04_11
. . . . . . . . . . . . . . . . . . . with 200S, syn214K, syn276H,
. . . . . . . . . . . . . . swIowa02999_2010_04_01,
. . . . . . . . . . . . . . UtahAF2653_2010_03_14
. . . . . . . . . . . . . . . . . . . with syn253V,
. . . . . . . . . . . . . . North Carolina05_2010_02_24
. . . . . . . . . . . . . . . . . . . with 259V,
. . . . . . . . . . . . . . Kentucky04_2010_02_22
. . . . . . . . . . . . . . . . . . . with syn488D,
. . . . . . . . . . . . . . Minnesota02_2010_02_17
. . . . . . . . . . . . . . . . . . . with 259V, 509D,
. . . . . . . . . . . . . . SouthCarolina01_2010_01_27
. . . . . . . . . . . . . . . . . . . with syn238E, syn488D,
. . . . . . . . . . . . . . AnasPlatBelgium04328_pcs17_2010_01_21
. . . . . . . . . . . . . . . . . . . with syn474C,
. . . . . . . . . . . . . . GermanyAF2208_2010_01_20
. . . . . . . . . . . . . . . . . . . with #1T, 225E,
. . . . . . . . . . . . . . NorthCarolina03_2010_01_20
. . . . . . . . . . . . . . . . . . . with 225G mix, 259V, syn275V,
. . . . . . . . . . . . . . NewMexico01_2010_01_05
. . . . . . . . . . . . . . . . . . . with 430I, syn445V, syn490P,
. . . . . . . . . . . . . . swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . with #1T, 0A, 189T, syn338G,
. . . . . . . . . . . . . . . . . . . . . . syn451K, syn474C, syn456L, syn529L,
. . . . . . . . . . . . . . Moldova5053_2009_12_11
. . . . . . . . . . . . . . . . . . with 173R, 176I, 225A, 225G mix wt, syn286K,
. . . . . . . . . . . . . . WiscD0128_2009_11_15
. . . . . . . . . . . . . . . . . . . with syn297N, syn343G, 471H,
. . . . . . . . . . . . . . KoreaAF2411_2009_11_11
. . . . . . . . . . . . . . . . . . . with 237I, syn286K,
. . . . . . . . . . . . . . England94840077_2009_11
. . . . . . . . . . . . . . . . . . . with 259T,
. . . . . . . . . . . . . . BahrainN11892_2009_10
. . . . . . . . . . . . . . . . . . . with 208K,
. . . . . . . . . . . . . . Nevada16_2009_10_02
. . . . . . . . . . . . . . . . . . . with 464R mix wt,
. . . . . . . . . . . . . . Tasmania2005_2009_07_03
. . . . . . . . . . . . . . . . . . . with 289M,
. . . . . . . . . . . . . . Texas42303371_2009
. . . . . . . . . . . . . . . . . . . with syn456L, syn507K],
. . . . . . . . syn449Y (TAc) [H3N8 Ttc],
. . . . . . . . syn474C [H3N8])

. . . . IranKaraj5327_2010_12_06 (
. . . . . . . . syn34N [JapanKanagawa74_2010_10_16, et al],
. . . . . . . . 146G [JapanKanagawa74_2010_10_16, et al],
. . . . . . . . 188T [H7N7],
. . . . . . . . 200T,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn465N [OzBrisbane209_51F_2010_08_09,
. . . . . . . . . . . . . . . . . . . . with 156E & 225G,
. . . . . . . . . . . . . . CalifVRDL131_2009_12_30, et al],
. . . . . . . . syn538F [Brunei218_2010 with 188T])

A significant correlation exists between syn474C and 137T.  26 of 42 sequences bearing syn474C also carry 137T.

Supporting Sequences

. . . . UKEngland4500186_2010_11_f (
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . 190Y [Avian H6N1],
. . . . . . . . . . [SwedenMalmoe1_2010_01_01_xL
. . . . . . . . . . . . with 377K, syn413K,
. . . . . . . . . . Brasil7450_2009_07_22
. . . . . . . . . . . . with 157E mix wt],
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . . . . . . [IranBandarAbbas5096_2010_10_02
. . . . . . . . . . . . . . . . . . . with 137T, 186P, syn474C,
. . . . . . . . . . . . . Florida13_2010_08_02
. . . . . . . . . . . . . . . . . . . with 137T, 186P, syn474C, 512M,
. . . . . . . . . . . . . . Iowa05_2010_05_04
. . . . . . . . . . . . . . . . . . . with 208K, syn516I,
. . . . . . . . . . . . . . swSouthDakota1_2010_04_27,
. . . . . . . . . . . . . . TexasAF2647_2010_04_11
. . . . . . . . . . . . . . . . . . . with 200S, syn214K, syn276H,
. . . . . . . . . . . . . . swIowa02999_2010_04_01,
. . . . . . . . . . . . . . UtahAF2653_2010_03_14
. . . . . . . . . . . . . . . . . . . with syn253V,
. . . . . . . . . . . . . . North Carolina05_2010_02_24
. . . . . . . . . . . . . . . . . . . with 259V,
. . . . . . . . . . . . . . Kentucky04_2010_02_22
. . . . . . . . . . . . . . . . . . . with syn488D,
. . . . . . . . . . . . . . Minnesota02_2010_02_17
. . . . . . . . . . . . . . . . . . . with 259V, 509D,
. . . . . . . . . . . . . . SouthCarolina01_2010_01_27
. . . . . . . . . . . . . . . . . . . with syn238E, syn488D,
. . . . . . . . . . . . . . AnasPlatBelgium04328_pcs17_2010_01_21
. . . . . . . . . . . . . . . . . . . with syn474C,
. . . . . . . . . . . . . . GermanyAF2208_2010_01_20
. . . . . . . . . . . . . . . . . . . with #1T, 225E,
. . . . . . . . . . . . . . NorthCarolina03_2010_01_20
. . . . . . . . . . . . . . . . . . . with 225G mix, 259V, syn275V,
. . . . . . . . . . . . . . NewMexico01_2010_01_05
. . . . . . . . . . . . . . . . . . . with 430I, syn445V, syn490P,
. . . . . . . . . . . . . . swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . with #1T, 0A, 189T, syn338G,
. . . . . . . . . . . . . . . . . . . . . . syn451K, syn474C, syn456L, syn529L,
. . . . . . . . . . . . . . Moldova5053_2009_12_11
. . . . . . . . . . . . . . . . . . with 173R, 176I, 225A, 225G mix wt, syn286K,
. . . . . . . . . . . . . . WiscD0128_2009_11_15
. . . . . . . . . . . . . . . . . . . with syn297N, syn343G, 471H,
. . . . . . . . . . . . . . KoreaAF2411_2009_11_11
. . . . . . . . . . . . . . . . . . . with 237I, syn286K,
. . . . . . . . . . . . . . England94840077_2009_11
. . . . . . . . . . . . . . . . . . . with 259T,
. . . . . . . . . . . . . . BahrainN11892_2009_10
. . . . . . . . . . . . . . . . . . . with 208K,
. . . . . . . . . . . . . . Nevada16_2009_10_02
. . . . . . . . . . . . . . . . . . . with 464R mix wt,
. . . . . . . . . . . . . . Tasmania2005_2009_07_03
. . . . . . . . . . . . . . . . . . . with 289M,
. . . . . . . . . . . . . . Texas42303371_2009
. . . . . . . . . . . . . . . . . . . with syn456L, syn507K],
. . . . . . . . syn408E,
. . . . . . . . syn474C,
. . . . . . . . 512M,
. . . . . . . . 530I)

. . . . UKEngland119_2010_11 (
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . 188N,
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . 391A,
. . . . . . . . syn408E,
. . . . . . . . syn474C,
. . . . . . . . 512M,
. . . . . . . . 530I)

. . . . UKEngland83_2010_10 (
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . syn272D,
. . . . . . . . syn279N,
. . . . . . . . syn352Y,
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . syn408E,
. . . . . . . . syn474C,
. . . . . . . . 509G,
. . . . . . . . 512M,
. . . . . . . . 530I)

. . . . UKEngland87_2010_10 (
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . syn279N,
. . . . . . . . syn352Y,
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . syn408E,
. . . . . . . . syn474C,
. . . . . . . . 509G,
. . . . . . . . 512M,
. . . . . . . . 530I)

. . . . UKEngland5500192_2010_10 (
. . . . . . . . 137T (aCA) [H3N8 donor aAT, aGT, aGC],
. . . . . . . . 186P [Avian H12 2008, 2009], [Avian H1N1],
. . . . . . . . syn279N,
. . . . . . . . syn352Y,
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . syn408E,
. . . . . . . . syn474C,
. . . . . . . . 509G,
. . . . . . . . 512M,
. . . . . . . . 530I)

. . . . Utah20_C2_2_2009_07_25_VxX (
. . . . . . . . #12E,
. . . . . . . . 0I [Latvia12_649_2009_12_09,
. . . . . . . . . NY7426_2009_12_08,
. . . . . . . . . Tambov_FOS_2009_12_01_xL,
. . . . . . . . . Slovenia5555_2009_12,
. . . . . . . . . Slovenia5559_2009_12,
. . . . . . . . . Ivanovo_RNA_2009_11_24_xL_f with 225G, 225N,
. . . . . . . . . Stockholm107_2009_11_24,
. . . . . . . . . GD_Yuncheng51_2009_11_19,
. . . . . . . . . Guangdong1271_2009_11_19,
. . . . . . . . . Austria528378_2009_11_19,
. . . . . . . . . Latvia11_1133_2009_11_16,
. . . . . . . . . Latvia11_1133M_2009_11_16,
. . . . . . . . . Latvia11_575_2009_11_11,
. . . . . . . . . England94600039_2009_10_27,
. . . . . . . . . SwedenUmea8_2009_10_07,
. . . . . . . . . Managua2323_02_2009_08_18,
. . . . . . . . . Texas42163291_2009_06_16,
. . . . . . . . . Marseille3416_2009],
. . . . . . . . 159D,
. . . . . . . . 206S,
. . . . . . . . 227G mix,
. . . . . . . . 296H,
. . . . . . . . syn388K [H5N1],
. . . . . . . . 470I)

. . . . Rome709_2009_07_14 (
. . . . . . . . 35I,
. . . . . . . . syn41N,
. . . . . . . . syn93C,
. . . . . . . . syn96G,
. . . . . . . . 206S,
. . . . . . . . 388M,
. . . . . . . . syn456L,
. . . . . . . . 516X (Ann),
. . . . . . . . 517X (nTG))

. . . . Aarhus241_2009_11_26_xL (
. . . . . . . . 176I, ** connecting Europe to North America xL **
. . . . . . . . syn177L,
. . . . . . . . 206T,
. . . . . . . . 324I,
. . . . . . . . syn383N [India PF11],
. . . . . . . . syn413K [H9N2])

. . . . IndiaPune21115_2009_12 (
. . . . . . . . syn147F [H3N8 Avian, H4, H5, H6, H11],
. . . . . . . . . . . . . . [Yaroslavl_KMP_2009_08_25,
. . . . . . . . . . . . . . IndiaJalna9436_2009_08_30 with 226R,
. . . . . . . . . . . . . . Texas44301765_2009_08_30,
. . . . . . . . . . . . . . CalifVRDL99_2009_11_05,
. . . . . . . . . . . . . . Athens943_2009_06_12],
. . . . . . . . syn163K,
. . . . . . . . 233H,
. . . . . . . . 271T,
. . . . . . . . 289V [Ukraine123_2010_02_14_xL with 230I,
. . . . . . . . . . . . .UK_Glascow_SC10_2009_06 with 225G, et al],
. . . . . . . . 377K [H9N2],
. . . . . . . . syn383N)

. . . . SwedenStockholm5_2010_08_27 (
. . . . . . . . 137T [41 sequences at GISAID],
. . . . . . . . syn163K,
. . . . . . . . 186P,
. . . . . . . . syn363G [21 sequences at GISAID],
. . . . . . . . syn474C,
. . . . . . . . 525G mix [Unique to GISAID; Unique to GenBank])

. . . . OzCanberra8_2010_08_15 (
. . . . . . . . 137T,
. . . . . . . . syn163K,
. . . . . . . . 186P,
. . . . . . . . syn363G,
. . . . . . . . syn397G,
. . . . . . . . syn474C)

. . . . Florida13_2010_08_02 (
. . . . . . . . 51T,
. . . . . . . . 137T,
. . . . . . . . 186P,
. . . . . . . . syn363G,
. . . . . . . . 377G,
. . . . . . . . syn474C,
. . . . . . . . 512M)

. . . . India007_2010_06_17 (
. . . . . . . . 137T,
. . . . . . . . syn163K,
. . . . . . . . 186P,
. . . . . . . . syn363G,
. . . . . . . . syn378I,
. . . . . . . . syn474C)

. . . . India3725_2010_04_03 (
. . . . . . . . 137T,
. . . . . . . . syn167S,
. . . . . . . . 186P,
. . . . . . . . syn474C,
. . . . . . . . syn526S [Malmoe2_2010_05_07 with 89G])

. . . . swItaly85437_2009_12_09 mix (
. . . . . . . . syn40H,
. . . . . . . . 225E,
. . . . . . . . 226R,
. . . . . . . . 300S,
. . . . . . . . syn434N,
. . . . . . . . syn474C,
. . . . . . . . 530I)

. . . . Salekhard01_2009_xL_f (
. . . . . . . . . . . 89N,
. . . . . . . . . . . 158E [H3N8, H5N1],
. . . . . . . . . . . 165N [H9N2],
. . . . . . . . . . . syn168Y [H9N2],
. . . . . . . . . . . 225G,
. . . . . . . . . . . syn413K [H9N2],
. . . . . . . . . . . 444D)

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

. . . . OzVictoria508_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])

. . . . Zhongyuan1643_2009_11_16 (131P, 208G, syn326S)

. . . . YaroslavlIIV196_2009_12_04_f (
. . . . . . . . . . . syn7C,
. . . . . . . . . . . 89G [H7N7],
. . . . . . . . . . . syn159N [H3N8, H9N2],
. . . . . . . . . . . 225G,
. . . . . . . . . . . syn297N [H5N1],
. . . . . . . . . . . syn319T [H5N1],
. . . . . . . . . . . syn428L [H5N1])

. . . . Australia6_2009_07_18 (
. . . . . . . . 89G [H7N7],
. . . . . . . . syn159N [H3N8, H9N2],
. . . . . . . . 233H,
. . . . . . . . syn297N [H5N1],
. . . . . . . . syn406R [1918, WSN33, S9, S7, M7])

. . . . CalifVRDL2_2010_01_11 (
. . . . . . . . syn121P,
. . . . . . . . syn193S [H3N8, H6N1],
. . . . . . . . 206T,
. . . . . . . . syn297N,
. . . . . . . . 377K [H9N2],
. . . . . . . . 502K [UkrTernopilN10_2009_10_28_xL_f with 225G,
. . . . . . . . . . . Oz_Victoria800_2010_06_02,
. . . . . . . . . . . SingGP2362_2010_05_18,
. . . . . . . . . . . Scandinavia (7),
. . . . . . . . . . . California33_2009_08_06,
. . . . . . . . . . . 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])

. . . . Brussels243_2009_11_09 (
. . . . . . . . #10T [KyrgyzstanBishkekWR0881T_2009_12_02,
. . . . . . . . . . . . IndiaPune9355_2009_08 with 225G,
. . . . . . . . . . . . IndiaPune8489_2009_08 with 237I,
. . . . . . . . . . . . IndiaPune6447_2009_08],
. . . . . . . . syn44L,
. . . . . . . . 89G [H7N7],
. . . . . . . . syn102E,
. . . . . . . . syn159N [H3N8, H9N2],
. . . . . . . . 202A,
. . . . . . . . 252L,
. . . . . . . . syn297N [H5N1],
. . . . . . . . syn323N,
. . . . . . . . syn413K [H2, H5N1, H9N2],
. . . . . . . . syn490P (CCg))

. . . . Tunisia1064_2010_01_18 (
. . . . . . . . syn30T,
. . . . . . . . syn181G,
. . . . . . . . syn182I,
. . . . . . . . 208K,
. . . . . . . . 225G,
. . . . . . . . 318S)

. . . . swThaiCURA4_2009_11 (
. . . . . . . . 226R,
. . . . . . . . 263D,
. . . . . . . . syn317L,
. . . . . . . . 318T,
. . . . . . . . syn350G,
. . . . . . . . 392H,
. . . . . . . . 414I,
. . . . . . . . syn484N)

. . . . Kansas03_2009_04_24_GQ168644 (
. . . . . . . . #1T,
. . . . . . . . syn161Y [H3N8 2009, H6N1, H9N2],
. . . . . . . . 186P mix,
. . . . . . . . syn456L)

. . . . Egypt114_2009_12_06 (
. . . . . . . . #1T,
. . . . . . . . 225E,
. . . . . . . . 300S,
. . . . . . . . 502K
. . . . . . . . syn512R)

. . . . SingGP2362_2010_05_18 (
[HA match to Oz_Victoria800_2010_06_02]
. . . . . . . . syn44L,
. . . . . . . . syn106E,
. . . . . . . . 128D,
. . . . . . . . 377K,
. . . . . . . . 502K,
. . . . . . . . syn529L (CTa) [UKWhiteChapel4880374_2010_11_28]

Lab Notes

377G
Origination Eval
[H2N3],
[H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
[H6N1 2009],
[Avian H1N1, tn]
[UKLiverpool_1951],
[1918]

H2N3 Extensive incl
swMO4296424_2006
avian Alaska 2007
avian MN 2008

H5N1 wt GGA
CAAAAGGCAATAGATGgG
CAAAgGGCAATAGATGgG = 4526
Indonesia160H_2005_11_08
EgyptN04823_4M_2009_05_25, Sharqeya
EgyptN04526_4M_2009_05_18, Daqahleya.
dkEgypt0877NLQP_2008_04_15
140727_muscdkViet48_2007

H6N1 wt GGA
tkBelgium1865/2009
tkBelgium19842/2008
mallMaryland887_2002
mallOhio249/1998
mallALB730/1981
tealAustralia1/1979
dkPA486/1969


1. Ellis J, Galiano M, Pebody R, Lackenby A, Thompson C, Bermingham A, McLean E, Zhao H, Bolotin S, Dar O, Watson JM, Zambon M. Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010/11. Euro Surveill. 2011;16(1):pii=19760. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19760

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

UK Severe Wave Demonstrates Diversity with Vaccine Escape Positional Changes

Last Updated 2011-01-12

The UK Health Protection Agency released a group of 37 sequences at GISAID dated 2010-01-05 that appeared sometime after that date. Some of the sequences in this deposit also appear on the Figure 3 Phylogenetic Tree from the HPA Eurosurveilance paper requested to be cited as:

Ellis J, Galiano M, Pebody R, Lackenby A, Thompson C, Bermingham A, McLean E, Zhao H, Bolotin S, Dar O, Watson JM, Zambon M. Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010/11. Euro Surveill. 2011;16(1):pii=19760.
Available online:
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19760
Date of submission: 31 December 2010

Amino acid positions 156, 158 and 159 have been tracked in the ΣPF11 reservoir with changes associated to multiple "Low Reactor" specimens. 

188T with 225G - UKEngland4880378_2010_12 [Link]
188T with 158E - UKEngland106_2010_11

Where is 188T with 158E and 225G similar to domained 156E, 188T and 225G on OzBrisbane209_51F_2010_08_09?

GeneWurx_UK_December_Emerging_Genetics_v4.xls

. . . . UKEngland106_2010_11 (
. . . . . . . . 0A,
. . . . . . . . syn55L,
. . . . . . . . 158E mix wt,
. . . . . . . . 188T,
. . . . . . . . syn258F [RussiaPermCREI_ZTS_2009_11_30
. . . . . . . . . . . . . . . . . . with 0A, 377K],
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . 452I [H3N8 nucleotide donor],
. . . . . . . . . . . . [H11 nucleotide donor],
. . . . . . . . 454N,
. . . . . . . . syn529L)

. . . . UKEngland3380426_2010_08 (
. . . . . . . . syn44L,
. . . . . . . . syn106E,
. . . . . . . . 128D,
. . . . . . . . 159K [NY3230_2010_01_25
. . . . . . . . . . . . with 100N, syn177L, syn231N],
. . . . . . . . 377K)

Though neither of these two UK sequences are specfied as "Low Reactor", their inclusion indicates not only the divergency of the reservoir at this point, but also the ongoing potential for Vaccine Escape.

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

UK Severe Wave Sequences Show No Fatalities with 225G

Last Updated 2011-01-12

The UK Health Protection Agency released a group of 37 sequences at GISAID dated 2010-01-05 that appeared sometime after that date. Some of the sequences in this deposit also appear on the Figure 3 Phylogenetic Tree from the HPA Eurosurveilance paper requested to be cited as:

Ellis J, Galiano M, Pebody R, Lackenby A, Thompson C, Bermingham A, McLean E, Zhao H, Bolotin S, Dar O, Watson JM, Zambon M. Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010/11. Euro Surveill. 2011;16(1):pii=19760.
Available online:
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19760
Date of submission: 31 December 2010

The science community expected a full deposit to back the paper, but not all sequences noted on the phylogenetic table were in place at GISAID as of this 2nd deposit.

The recent GISAID deposit added 4 of the fatalities noted on the Ellis Figure3 ¹ phylogenetic tree to the 4 fatalities previously released on 2010-12-20.  The previously released sequences were not marked at GISAID with a fatality notation, but now have been notated as "Deceased" as of yesterday.  Oddly enough, on the 2010-01-05 deposit, none of the sequences notated as fatal on the phylogenetic tree were marked as to outcome at GISAID?  This dys-synchronicity and cycling of outcome data is less than optimal for worldwide communication.

None of the sequences at the GISAID database that correspond to notated fatalities on the Eurosurveillance paper carry the severity marker of HA 225G.

225G is found on identical HA sequences noted as 2 severe cases.

• UKEngland4940476_2010_12
• UKEngland4880378_2010_12

. . . . UKEngland4940476_2010_12 (
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg) [Regional Marker 2009 (tTA)]
. . . . . . . . . . . . . . . . . . . . [TexasAF2588_2009_10_04,
. . . . . . . . . . . . . . . . . . . . TexasJMS404_2010_01_08],
. . . . . . . . 188T,
. . . . . . . . 225G,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L [Regional Marker 2009]
. . . . . . . . . . . . . . . [UKEngland4880378_2010_12 with syn179L, 188T,
. . . . . . . . . . . . . . . UKEngland4640543_2010_11_f with syn179L, 188T, 190G
. . . . . . . . . . . . . . . UKEngland4920303_2010_11 with syn179L, 188T,
. . . . . . . . . . . . . . . UKEngland142_2010_11 with syn179L, 188T,
. . . . . . . . . . . . . . . UKEngland4860049_2010_11 with syn179L, 188T,
. . . . . . . . . . . . . . . UKEngland126_2010_11 with syn179L, 188T,
. . . . . . . . . . . . . . . NZChristchurch8_2010_07_08
. . . . . . . . . . . . . . . . . . . with syn44L, 97N, syn99I, syn106E, 128D,
. . . . . . . . . . . . . . . . . . . . . . . syn214K, 253A, syn362S, 377K,
. . . . . . . . . . . . . . . Calif06_2010_04_05 with 269V
. . . . . . . . . . . . . . . Hawaii08_2010_04_12
. . . . . . . . . . . . . . . . . . . with 159D, 269V, 312R, 313K,
. . . . . . . . . . . . . . . Ethiopia13_2010_02_10
. . . . . . . . . . . . . . . . . . . with 100N, syn163K, 269V, 324I, syn360Q, syn455Q,
. . . . . . . . . . . . . . . Philippines824_2010_02_17 with 165N,
. . . . . . . . . . . . . . . Kosova876_2009_12_22,
. . . . . . . . . . . . . . . RussiaYakutsk_EAV_2009_11_18,
. . . . . . . . . . . . . . . Netherlands2143_2009_11_16 with syn179L (tTA),
. . . . . . . . . . . . . . . RussiaYaroslavl_CHMV_2009_11_10_f with 224K & 225G mix
. . . . . . . . . . . . . . . AntwerpINS221_2009_10_28 with syn179L (tTA)],
. . . . . . . . 454N)

. . . . UKEngland4880378_2010_12 (
. . . . . . . . 100N,
. . . . . . . . syn179L,
. . . . . . . . 188T,
. . . . . . . . 225G,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L,
. . . . . . . . 454N)

With 8 fatalities noted on the tree and none of them coming from cases manifesting an HA 225G severity marker, we must ask for more data while looking elsewhere for causality.  The common theme in recent UK and other geographies is hyper-zoonosis creating divergency.  Animal reservoirs (H3N8, H5N1, H7N7) carry change values matching the recent intake into the pH1N1 circulation.  Data suggests that this human disease is rapidly diversifying by accumulating genetic information from multiple animal reservoirs.

For example, the 377G that is emergent in 2009 Human H5N1 from Dakahlia, Egypt is also emergent in England and Iran in the Pandemic H1N1 reservoir. A recent fatal case from England, UKEngland4500186_2010_11_f, carries the same coding for 377G combined with a 190Y that is found only elsewhere in 2010 Malmoe, Sweden pH1N1, in early pH1N1 with HA 157E in Brasil and in Avian H6N1.

. . . . UKEngland4500186_2010_11_f  (
. . . . . . . . 137T,
. . . . . . . . 186P,
. . . . . . . . 190Y [Avian H6N1],
. . . . . . . . . . [SwedenMalmoe1_2010_01_01_xL
. . . . . . . . . . . . with 377K, syn413K,
. . . . . . . . . . Brasil7450_2009_07_22
. . . . . . . . . . . . with 157E mix wt],
. . . . . . . . 377G [H2N3],
. . . . . . . . . . . . . [H5N1 Human Egypt Preschool 2009, H5N1 Human Indonesia 2005],
. . . . . . . . . . . . . [H6N1 2009],
. . . . . . . . . . . . . [US Swine 1957-1978],
. . . . . . . . . . . . . [IranBandarAbbas5096_2010_10_02
. . . . . . . . . . . . . . . . . . . with 137T, 186P, syn474C,
. . . . . . . . . . . . . Florida13_2010_08_02
. . . . . . . . . . . . . . . . . . . with 137T, 186P, syn474C, 512M,
. . . . . . . . . . . . . . Iowa05_2010_05_04
. . . . . . . . . . . . . . . . . . . with 208K, syn516I,
. . . . . . . . . . . . . . swSouthDakota1_2010_04_27,
. . . . . . . . . . . . . . TexasAF2647_2010_04_11
. . . . . . . . . . . . . . . . . . . with 200S, syn214K, syn276H,
. . . . . . . . . . . . . . swIowa02999_2010_04_01,
. . . . . . . . . . . . . . UtahAF2653_2010_03_14
. . . . . . . . . . . . . . . . . . . with syn253V,
. . . . . . . . . . . . . . North Carolina05_2010_02_24
. . . . . . . . . . . . . . . . . . . with 259V,
. . . . . . . . . . . . . . Kentucky04_2010_02_22
. . . . . . . . . . . . . . . . . . . with syn488D,
. . . . . . . . . . . . . . Minnesota02_2010_02_17
. . . . . . . . . . . . . . . . . . . with 259V, 509D,
. . . . . . . . . . . . . . SouthCarolina01_2010_01_27
. . . . . . . . . . . . . . . . . . . with syn238E, syn488D,
. . . . . . . . . . . . . . AnasPlatBelgium04328_pcs17_2010_01_21
. . . . . . . . . . . . . . . . . . . with syn474C,
. . . . . . . . . . . . . . GermanyAF2208_2010_01_20
. . . . . . . . . . . . . . . . . . . with #1T, 225E,
. . . . . . . . . . . . . . NorthCarolina03_2010_01_20
. . . . . . . . . . . . . . . . . . . with 225G mix, 259V, syn275V,
. . . . . . . . . . . . . . NewMexico01_2010_01_05
. . . . . . . . . . . . . . . . . . . with 430I, syn445V, syn490P,
. . . . . . . . . . . . . . swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . with #1T, 0A, 189T, syn338G,
. . . . . . . . . . . . . . . . . . . . . . syn451K, syn474C, syn456L, syn529L,
. . . . . . . . . . . . . . Moldova5053_2009_12_11
. . . . . . . . . . . . . . . . . . with 173R, 176I, 225A, 225G mix wt, syn286K,
. . . . . . . . . . . . . . WiscD0128_2009_11_15
. . . . . . . . . . . . . . . . . . . with syn297N, syn343G, 471H,
. . . . . . . . . . . . . . KoreaAF2411_2009_11_11
. . . . . . . . . . . . . . . . . . . with 237I, syn286K,
. . . . . . . . . . . . . . England94840077_2009_11
. . . . . . . . . . . . . . . . . . . with 259T,
. . . . . . . . . . . . . . BahrainN11892_2009_10
. . . . . . . . . . . . . . . . . . . with 208K,
. . . . . . . . . . . . . . Nevada16_2009_10_02
. . . . . . . . . . . . . . . . . . . with 464R mix wt,
. . . . . . . . . . . . . . Tasmania2005_2009_07_03
. . . . . . . . . . . . . . . . . . . with 289M,
. . . . . . . . . . . . . . Texas42303371_2009
. . . . . . . . . . . . . . . . . . . with syn456L, syn507K],
. . . . . . . . syn408E,
. . . . . . . . syn474C,
. . . . . . . . 512M,
. . . . . . . . 530I)

The HPA Ellis Figure3 ¹ phylogenetic tree did not notate the 377G branch though 5 English sequences, including this fatal one, appear on the chart carrying the H5N1 Human adaptation.

• UKEngland83_2010_10
• UKEngland87_2010_10
• UKEngland5500192_2010_10
• UKEngland119_2010_11
• UKEngland4500186_2010_11_f

GeneWurx has annotated the Ellis Figure3 ¹ phylogenetic tree with green boxes next to the four fatal GISAID 2010-12-20 deposited sequences and has proposed polymorphism notations on various unmarked branches in an attempt to provide clarity.

UK_2010_Phylo_ELLIS_Fig3new_4_GISAID_Notated_2011_01_08.JPG

Is the Hydra Effect providing Immune Escape capacity for this circulating viral reservoir?  Has an accelerant been insinuated into the reservoir?

In many locales around the United Kingdom, half of the ICU beds are occupied by Influenza patients.  Only 1 of 12 ICU beds was occupied by an Influenza patient at the peak of last year's pandemic.  100% of the ECMO capacity (heart/lung machine) has been utilised for more than 2 weeks.  Hospitals have moved to "Black Alert" status.  Ireland has set new records for the number of ER (Casualty, A&E) patients left on gurneys due to room capacity problems. 

Do these facts move the HPA to quickly derive plausible causality and workable next steps?

Usable data streams with matched clinicals to the sequences are the primary inputs required to investigate and validate causality.  An explanation is deserved from the HPA on their removal of this valuable data from the science community?

Supporting Sequences


. . . . Florida13_2010_08_02 (
. . . . . . . . 51T,
. . . . . . . . 137T,
. . . . . . . . 186P,
. . . . . . . . syn363G,
. . . . . . . . 377G,
. . . . . . . . syn474C,
. . . . . . . . 512M)

. . . . SwedenMalmoe1_2010_01_01_xL (
. . . . . . . . 190Y mix wt [Avian H6N1],
. . . . . . . . 324I,
. . . . . . . . 377K,
. . . . . . . . syn413K)

. . . . Brasil7450_2009_07_22 (
. . . . . . . . 157E mix wt,
. . . . . . . . 190Y [Avian H6N1])


1. Ellis J, Galiano M, Pebody R, Lackenby A, Thompson C, Bermingham A, McLean E, Zhao H, Bolotin S, Dar O, Watson JM, Zambon M. Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010/11. Euro Surveill. 2011;16(1):pii=19760. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19760

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

Fatal Divergency on 4 UK Zoonotic Sequences

The UK Health Protection Agency released an analysis of the early severe wave today in Eurosurveillance. The requested citation is:

Ellis J, Galiano M, Pebody R, Lackenby A, Thompson C, Bermingham A, McLean E, Zhao H, Bolotin S, Dar O, Watson JM, Zambon M. Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010/11. Euro Surveill. 2011;16(1):pii=19760.
Available online:
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19760
Date of submission: 31 December 2010

No additional sequences appear to have been released with the paper though a very useful phylogenetic chart is provided as Figure 3: Phylogenetic relationship of full-length HA sequences of influenza A(H1N1)2009 viruses from fatal, severe and mild cases in the United Kingdom during 2010.

All four previously released UK sequences from 2010-12-20 are on the Ellis Figure3 ¹ chart marked as fatality and all four were updated yesterday on GISAID as "Deceased".  Two were recent and all four are divergent.

Fatal Sequences from Ellis Figure 3 In GISAID 2010-12-20 Deposit

* UKWhiteChapel4880374_2M_2010_11_28_f	= A/England/4880374/2010
* UKCambridge118_4F_2010_11_19_f	= A/England/118/2010
* UKWhiteChapel4780352_5M_2010_10_26_f	= A/England/4780352/2010
* UKBirmingham3220137_44F_2010_08_07_f	= A/England/3220137/2010

GeneWurx has annotated the Ellis Figure3 ¹ phylogenetic chart with green boxes next to the four fatal GISAID 2010-12-20 deposited sequences and has proposed a 225G branch due to lack of data transparency.

• UK_2010_Phylo_ELLIS_Fig3new_4_GISAID_Notated.jpg
• GeneWurx_UK_December_Emerging_Genetics_v3.xls

Preliminary Comments on the Ellis Figure 3
(without the essential corroborating sequences)

The numbering system employed in our analyses requires adding 3 to the amino acid positions indicated in the UK chart. 

Notice that the branch polymorphisms are not labeled from that top D97N (100N) upwardly.

The accumulation of 100N, 188T, 377K, 225G and 454N patterns onto the OzBrisbane209_51F_2010_08_09 sequence from the late winter in the Southern Hemisphere.  Though parameters are adjustable for the phylogenetic chart, the top section may indicate one or more unmarked branches near the top right.  Either publication of the sequences or the notation for the branching polymorphism would be very useful at this time.  Are these strictly indicative of the high variability head and tail changes being seen frequently (under aa100, over aa499)?

Is it probable that no instance of change at any amino acid position from 156 to 159 has been elucidated from this wide inspection of the severe wave?

Alternate sub-clade:

By chart appearances, the accumulation of 128D onto the more established backgrounds with 100N and 377K (lower section) creates a fatality risk similar to more recognised severity markers. The bottom fatal sequence designated on the lower branch as A/England/4780352/2010 is identified as UKWhiteChapel4780352_2010_10_26_f in v3 of the GeneWurx Emerging Genetics spreadsheet within column AY and carries three additional silent (synonymous) changes at syn58C, syn131S and syn210S.

Hyper-Zoonotic Polymorphism Details

Please excuse the intermediate markings on these sequences. The following are rough lab notes, but divergence may be ascertained easily.

The common ground among these sequences and those in the database on either side of them temporally, from Cameroon (Sub-clade 1 & Sub-clade 2) and especially Iran, is the high quantity of polymorphisms that are novel or rare to pH1N1 and that also appear in zoonotic reservoirs, particularly H3N8, H5N1 and H7N7.

Even small genetic adjustments from animal vectors into human infections, especially H3N8, may create variant behaviour. This potential era of zoonotic sub-segment spillover merits as much investigation for severity (in combination) as does the recognised 225G.

. . . . UKWhiteChapel4880374_2M_2010_11_28_f (
. . . . . . . . 0A (gCC) [1918 (GCT), S7 (GCT), S5 (GCA)]
. . . . . . . . syn55L [S9, H5N1],
. . . . . . . . . . . . . . [Darwin47_2010_08_09 with syn529L,
. . . . . . . . . . . . . . Iran16273_2009_11_22 with 226R
. . . . . . . . . . . . . . NZ_Waikato2_2010_01_04 with 233H,
. . . . . . . . . . . . . . tkOntarioFAV117_1C_2009_12_07 mult domain matches, et al],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . . . . . . . . [OzBrisbane209_51F_2010_08_09
. . . . . . . . . . . . . . . . . . . . with 156E & 225G,
. . . . . . . . . . . . . . . Arizona05_2010_05_11 with 0A,
. . . . . . . . . . . . . . . Swine Asia 2005 with 0A, 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, et al],
. . . . . . . . syn529L (CTt) [Unique to PF11]
. . . . . . . . . . . . . . . . . . . . [S7 (CTt), tn with syn338G (GGg)]
. . . . . . . . . . . . . . . . . . . . [PF11 32 Worldwide (CTa),
. . . . . . . . . . . . . . . . . . . . PF11 5 North America (tTG)],
. . . . . . . . . . . . . . . . . . . . [swThailandCU_CHK4_2009_01 (tTG)
. . . . . . . . . . . . . . . . . . . . . . . . . . with 0A, syn338G, 189T, 377G, syn451K, syn456L])

. . . . UKCambridge118_4F_2010_11_19_f (
. . . . . . . . syn118E tcatttgaaaggtttgaA,
. . . . . . . . 137T [MoldovaG170_2009,
. . . . . . . . . . . . . 41 sequences at GISAID],
. . . . . . . . syn163K,
. . . . . . . . 186P,
. . . . . . . . syn251L gaagcaactggaaatctG,
. . . . . . . . syn293L gctataaacaccagcctT,
. . . . . . . . syn363G [21 sequences at GISAID],
. . . . . . . . syn455Q caAttaaaaaacaatgcc ,
. . . . . . . . syn474C [H3N8],
. . . . . . . . 504G ttaaacagagaagaaatagGt,
. . . . . . . . 513V [1918, S5, tn] Gtttaccagattttggcgatc)

. . . . UKWhiteChapel4780352_5M_2010_10_26_f (
. . . . . . . . syn58C,
. . . . . . . . 100N,
. . . . . . . . 128D,
. . . . . . . . syn131S tcaaacaaaggtgtaacggca,
. . . . . . . . syn210S,
. . . . . . . . 377K)

. . . . UKBirmingham3220137_44F_2010_08_07_f (
. . . . . . . . #8A gcagttctgctatatacattt,
. . . . . . . . 175K aaagtcctcgtgctatgg,
. . . . . . . . 311E Gaaagcacaaaattgaga,
. . . . . . . . 377K,
. . . . . . . . syn385V gtCattgaaaagatgaat,
. . . . . . . . syn451K aagaacttatatgaaaaA,
. . . . . . . . syn454S agTcagttaaaaaacaatgcc,
. . . . . . . . syn494E,
. . . . . . . . 537G [S5] tccctgggggcaatcGgt)

1. Ellis J, Galiano M, Pebody R, Lackenby A, Thompson C, Bermingham A, McLean E, Zhao H, Bolotin S, Dar O, Watson JM, Zambon M. Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010/11. Euro Surveill. 2011;16(1):pii=19760. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19760

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

UK Sequences from 2009 Document Transmission of TamiFlu Resistance

The UK Health Protection Agency released a set of 38 English sequences on 2010-01-04 at GenBank, but not from the current 2010 severe wave. These 38 HA and NA publications are delayed more than one year, covering September 10 to November 25, 2009. No sequences are included from the pandemic wave currently circulating.

65% of the English sequences are cross-linked with HA syn413K and NA syn407V.  225E occurs in 5 sequences and 225G in 2 sequences. Person to person transmission of oseltamivir-resistance via NA H275Y is noted within a hematology unit that encompasses 15 of these 38 sequences. All but one of the anti-viral resistant sequences are on a cross-linked background. One simple drug resistant sequence carries 225G on the cross-linked background.

The drug-resistant 15 are unremarkable, but for their simplicity.  The 225G sequences and a representative sample of the anti-viral resistant sequences is presented after the complete listing of TmX sequence names sorted by date.


TamiFlu-Resistance by Date

• UKEngland94640080_2009_11_04_xL_TmX
• UKEngland94640078_2009_11_05_xL_TmX
• UKEngland94740137_2009_11_07_xL_TmX
• UKEngland00380009_2009_11_07_xL_TmX
• UKEngland94740049_2009_11_10_xL_TmX
• UKEngland94740139_2009_11_10_xL_TmX
• UKEngland00380013_2009_11_12_xL_TmX
• UKEngland94740138_2009_11_16_xL_TmX
• UKEngland94740140_2009_11_16_xL_TmX
• UKEngland94780019_2009_11_17_xL_TmX
• UKEngland00380015_2009_11_17_xL_TmX
• UKEngland00380018_2009_11_19_xL_TmX
• UKEngland94840152_2009_11_19_TmX
• UKEngland00380020_2009_11_20_xL_TmX
• UKEngland94840153_2009_11_20_xL_TmX

Representative Sequences

. . . . UKEngland93960032_2009_09_10_xL (
. . . . . . . . 225G,
. . . . . . . . 273A,
. . . . . . . . syn413K)

. . . . UKEngland94640080_2009_11_04_xL_TmX (
. . . . . . . . syn77S,
. . . . . . . . 225G,
. . . . . . . . syn413K)

. . . . UKEngland94740049_2009_11_10_xL_TmX (
. . . . . . . . syn77S,
. . . . . . . . syn413K,
. . . . . . . . 475N mix wt)

. . . . UKEngland00380018_2009_11_19_xL_TmX (
. . . . . . . . syn77S,
. . . . . . . . syn96G,
. . . . . . . . 237I,
. . . . . . . . syn413K)

. . . . UKEngland94840152_2009_11_19_TmX (
. . . . . . . . syn77S)

. . . . UKEngland94840153_2009_11_20_xL_TmX (
. . . . . . . . syn77S,
. . . . . . . . syn331G,
. . . . . . . . syn413K)

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

Cameroon 230I Permissive Sequences Carry H3N8 and H7N7 Zoonotic Matches

Recently published sequences from Cameroon show homology to backgrounds that have supported HA 230I.  Several of these backgrounds carry homology to animal reservoirs and Cameroon follows suit.  These two young boys, ages 10 and 7, who were part of a transmission chain extended over 13 days may or may not have had close contact with animals. Cameroon10v_00812_7M_2010_03_23 is an exact HA match with Cameroon10v_00751_10M_2010_03_10.

The sequences are potentially related to the severe wave in the UK that has filled hospitals and, more importantly, Intensive Care Units to capacity placing many large medical trusts into "black" alert.  English elective surgeries are actively being cancelled.  Families are being told not to attempt a hospital visit in the case of Influenza due to the infrastructure strain.  Emergency departments are forced to place patients on gurneys due to no beds being available while operating theatres and lounges are being hastily converted to patient rooms.

Animal influences on the genetics of human-infecting Influenza like the pH1N1 strain may generate extreme outcomes and variant clinical behaviour. In these cases from Cameroon, the syn350G, 457R, syn461K and syn466G, among others, share homology with animal reservoirs as noted on the sequence details. We have discussed widely the HA 188T found in the emerging sub-clade including Australia, the UK and Iran. HA 188T is also found in the H7N7 reservoir, as is the syn350G on these Cameroon sequences.

The 457R and syn466G appear together within the H3N8 reservoir and are paired on a particularly interesting set of related horse and dog sequences from Australia.  These two changes fall into a domain band that is related to the emerging sub-clade from Australia to the UK.

• canineSydney6525_2007_10_14
• canineSydney6692_2007_10_15
• equineSydney6085_2007_10_10

GeneWurx_UK_December_Emerging_Genetics_v3.xls

. . . . Cameroon10v_00812_7M_2010_03_23 (
. . . . . . . . 100N [UKWhiteChapel4780352_2010_10_26
. . . . . . . . . . . . . . . . with 128D, syn131S, syn210S, 377K],
. . . . . . . . syn137A [UKCambridge118_2010_11_19
. . . . . . . . . . . . . . . . . . . . with syn363G, syn455Q, syn474C,
. . . . . . . . . . . . . . . . NorthCarolina56_2009_12_07
. . . . . . . . . . . . . . . . . . . . with 100N, 377K],
. . . . . . . . 218V [Minnesota04_18M_2010_03_22
. . . . . . . . . . . . . . . . with 165N, 230I, syn346G,
. . . . . . . . . . . . . Pennsylvania14_20M_2009_06_07
. . . . . . . . . . . . . . . . with 158E, 523I],
. . . . . . . . syn270I,
. . . . . . . . syn343G,
. . . . . . . . syn350G [H7N3, H7N7],
. . . . . . . . . . . [IranShiraz1_2010_02
. . . . . . . . . . . . . . . with 218A, 228R,
. . . . . . . . . . . swThaiCURA4_2009_11
. . . . . . . . . . . . . . . with 226R, syn484N],
. . . . . . . . 377K,
. . . . . . . . 457R [H2N3, H3N8, H4, H5N1, H7N3],
. . . . . . . . . . . . . [swJapanOkinawa2_2005
. . . . . . . . . . . . . . . . . . . with 225G],
. . . . . . . . syn461K [H2N3, H5N1 Human, Civet & Avian, H6N1, H11],
. . . . . . . . . . . . . . .  [Iran16273_2009_11_22
. . . . . . . . . . . . . . . . . . . . with syn55L, 226R],
. . . . . . . . syn466G [H2N3, H3N8, H4N8, H6N1, H7N3, H9N2, H10N7],
. . . . . . . . . . . . . . . [cheetahCA30954_2009_11_17
. . . . . . . . . . . . . . . . . . . . with syn169I, 200S])

. . . . Cameroon10v_00751_10M_2010_03_10 (
. . . . . . . . 100N,
. . . . . . . . syn137A,
. . . . . . . . 218V,
. . . . . . . . syn270I,
. . . . . . . . syn343G,
. . . . . . . . syn350G,
. . . . . . . . 377K,
. . . . . . . . 457R,
. . . . . . . . syn461K,
. . . . . . . . syn466G)

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

UK Homology on Cameroon Pair Carrying 230I Permissive SNPs

The UK National Institute for Medical Research published a group of sequences on 2010-12-30 at GISAID.  One group originated from the Centre Pasteur du Cameroun.

Two young boys, ages 10 and 7, are part of a transmission chain extended over 13 days. Cameroon10v_00812_7M_2010_03_23 is an exact HA match with Cameroon10v_00751_10M_2010_03_10.

These two sequences carry genetics common to the most recent October and November 2010 UK sequences while combining polymorphisms associated with RBD changes including 230I.  Using domaining produces a clear relationship between Cameroon and the 230I carrier and 230I permissive sequences.  Simple scrolling of the provided spreadsheet demonstrates the relationships.

GeneWurx has prepared an Excel spreadsheet investigating potential genetic acquisition in the currently uncharted severe Pandemic H1N1 wave in the UK.  In Version 3 of this spreadsheet, this Cameroon representative sequence, Cameroon10v_00812_7M_2010_03_23, takes Column U and provides homology with UK sequences of recent interest.

GeneWurx_UK_December_Emerging_Genetics_v3.xls

. . . . Cameroon10v_00812_7M_2010_03_23 (
. . . . . . . . 100N [UKWhiteChapel4780352_2010_10_26
. . . . . . . . . . . . . . . . with 128D, syn131S, syn210S, 377K],
. . . . . . . . syn137A [UKCambridge118_2010_11_19
. . . . . . . . . . . . . . . . . . . . with syn363G, syn455Q, syn474C,
. . . . . . . . . . . . . . . . NorthCarolina56_2009_12_07
. . . . . . . . . . . . . . . . . . . . with 100N, 377K],
. . . . . . . . 218V [Minnesota04_18M_2010_03_22
. . . . . . . . . . . . . . . . with 165N, 230I, syn346G,
. . . . . . . . . . . . . Pennsylvania14_20M_2009_06_07
. . . . . . . . . . . . . . . . with 158E, 523I],
. . . . . . . . syn270I,
. . . . . . . . syn343G,
. . . . . . . . syn350G [H7N3, H7N7],
. . . . . . . . . . . [IranShiraz1_2010_02
. . . . . . . . . . . . . . . with 218A, 228R,
. . . . . . . . . . . swThaiCURA4_2009_11
. . . . . . . . . . . . . . . with 226R, syn484N],
. . . . . . . . 377K,
. . . . . . . . 457R [H2N3, H3N8, H4, H5N1, H7N3],
. . . . . . . . . . [swJapanOkinawa2_2005
. . . . . . . . . . . . . . . . with 225G],
. . . . . . . . syn461K [H2N3, H5N1 Human, Civet & Avian, H6N1, H11],
. . . . . . . . . . . . [Iran16273_2009_11_22
. . . . . . . . . . . . . . . . with syn55L, 226R],
. . . . . . . . syn466G [H2N3, H3N8, H4N8, H6N1, H7N3, H9N2, H10N7],
. . . . . . . . . . . . [cheetahCA30954_2009_11_17
. . . . . . . . . . . . . . . . with syn169I, 200S])

. . . . Cameroon10v_00751_10M_2010_03_10 (
. . . . . . . . 100N,
. . . . . . . . syn137A,
. . . . . . . . 218V,
. . . . . . . . syn270I,
. . . . . . . . syn343G,
. . . . . . . . syn350G,
. . . . . . . . 377K,
. . . . . . . . 457R,
. . . . . . . . syn461K,
. . . . . . . . syn466G)

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

HA 158E in Cameroon Pair with Additional HA Changes Correlated to Anti-Viral Resistance

The UK National Institute for Medical Research published a group of sequences on 2010-12-30 at GISAID.  One group originated from the Centre Pasteur du Cameroun.

HA 158E, a polymorphism associated with Vaccine Escape, appears in two Cameroon sequences upon a highly plastic background that is demonstrated worldwide, including multiple non-adjacent, coastal areas of the United States and in Australia on a background that may be permissive to HA 230I.

This Cameroon background has additionally been conserved in domestic poultry Pandemic H1N1 from Canada.

The most recent sequence taken in April 2010, Cameroon10v_1090_2010_04_08, also carries HA syn223V just upstream of the 225 amino acid position that is so often tracked.  HA syn223V has been co-located with 454N in Texas45131774_2009_09_13.  454N and other changes at 454 are highly correlated to the most recent UK sequences on file and to a chain of sequences spanning Australia before the UK and Iran after the UKWhiteChapel4880374_2M_2010_11_28 sample.  The related hypermorphic Australian sequence, OzVictoria508_9F_2010_07_24, shares 8 changes with Cameroon.

Notice that the syn254P has been found on a Japanese TamiFlu Resistant sequence.  523A, which is found at various points on Vaccine Escape and TamiFlu Resistant sequences, is also contained within the potential UK donation reservoir from Australia.

Based on these updates from NIMR, potential exists for a 158E emergence in the UK.

GeneWurx has prepared an Excel spreadsheet investigating potential genetic acquisition in the currently uncharted severe Pandemic H1N1 wave in the UK.  In Version 2 of this spreadsheet, the Cameroon 158E sequence takes Column W and provides homology with potential predecessors to one UK White Chapel sequence of interest.

GeneWurx_UK_December_Emerging_Genetics_v2.xls

. . . . Cameroon10v_1090_2010_04_08 (
. . . . . . . . 35I,
. . . . . . . . 114L,
. . . . . . . . syn152I,
. . . . . . . . 158E,
. . . . . . . . syn219I,
. . . . . . . . syn223V [Thailand34_9913_2010_07_14,
. . . . . . . . . . . . . . Texas45131774_2009_09_13],
. . . . . . . . syn254P [Kumamoto2_2010_01_14_TmX],
. . . . . . . . syn276H,
. . . . . . . . syn402H,
. . . . . . . . syn419L,
. . . . . . . . syn456L,
. . . . . . . . 463V,
. . . . . . . . 523A [OzSydney217_2010_09_19 with 188T,
. . . . . . . . . . . . . OzVictoria508_9F_2010_07_24,
. . . . . . . . . . . . . Montana02_2010_04_07_VxX,
. . . . . . . . . . . . . Shizuoka_C21_2010_01_20_TmX])

. . . . Cameroon10v_813_2010_03_23 (
. . . . . . . . 35I,
. . . . . . . . syn152I,
. . . . . . . . 158E mix wt,
. . . . . . . . syn219I,
. . . . . . . . syn254P,
. . . . . . . . syn276H,
. . . . . . . . HA truncated after aa396)

Supporting Sequences

. . . . OzVictoria508_9F_2010_07_24 (
. . . . . . . . 35I [H5N1],
. . . . . . . . 88P [H2N3, H5N1, H11],
. . . . . . . . . . . [HunanHechengSWL1616_2009-11-23,
. . . . . . . . . . . KoreaAF2376_2009_10_27
. . . . . . . . . . . . . . . with 280A and 290K
. . . . . . . . . . . Nevada15_9F_2009_09_10
. . . . . . . . . . . . . . . with 22I, 225E, 256F, 299Y,
. . . . . . . . . . . . . . . . . . 299Y, 300S, syn384S,
. . . . . . . . . . . GermanyCologne13_2009_06_29
. . . . . . . . . . . . . . . with 35I, 38V, syn108L,
. . . . . . . . . . . . . . . . . . syn205G, 206s, syn276H],
. . . . . . . . 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 [1918, S5],
. . . . . . . . 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 [H5N1],
. . . . . . . . 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])

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

. . . . FL_Pen213_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)

. . . . KoreaAF2376_2009_10_27 (
. . . . . . . . 88P [H2N3, H5N1, H11],
. . . . . . . . . . . . [Victoria508_2010_07_24 with ext changes,
. . . . . . . . . . . HunanHechengSWL1616_2009-11-23,
. . . . . . . . . . . Nevada15_9F_2009_09_10,
. . . . . . . . . . . GermanyCologne13_2009_06_29],
. . . . . . . . 131P,
. . . . . . . . 280A,
. . . . . . . . 290K [HunanHechengSWL1617_2009_11_23],
. . . . . . . . HA truncated after aa386)

. . . . Nevada15_9F_2009_09_10 (
. . . . . . . . 22I,
. . . . . . . . 88P,
. . . . . . . . 225E,
. . . . . . . . 256F,
. . . . . . . . 299Y,
. . . . . . . . 300S,
. . . . . . . . syn384S)

. . . . GermanyCologne13_2009_06_29 (
. . . . . . . . HA truncated until aa28,
. . . . . . . . 35I,
. . . . . . . . 38V,
. . . . . . . . 88P,
. . . . . . . . syn108L,
. . . . . . . . syn205G,
. . . . . . . . 206S,
. . . . . . . . syn276H,
. . . . . . . . HA truncated after aa321)

. . . . 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,
. . . . . . . . . . . . . . FL_Pen210_2009_11_10 with 225E]),

. . . . Shizuoka_C21_2010_01_20_TmX (
. . . . . . . . 22I,
. . . . . . . . syn149K,
. . . . . . . . syn413K,
. . . . . . . . 523A [Extensive US 2010 April & May (10),
. . . . . . . . . . . . on entirely different background,
. . . . . . . . . . . . including Montana02_2010_04_07_VxX]),

. . . . Kumamoto2_2010_01_14_TmX (
. . . . . . . . syn10Y [China22811_2009_12
. . . . . . . . . . . . . . . . . . . with 14 HA changes],
. . . . . . . . 252L [Maryland03_2010_01_13,
. . . . . . . . . . . . Guangdong2361_2009_11_25],
. . . . . . . . syn254P [1918, tn, H5N1]),
. . . . . . . . . . . . . . [Ancona451_2009_11_27_f,
. . . . . . . . . . . . . . Iran15583_2009_11_21
. . . . . . . . . . . . . . . . . . with 16 HA (226R) + 3 NA changes,
. . . . . . . . . . . . . . Iran16677_2009_11_24],
. . . . . . . . syn320G [H5N1],
. . . . . . . . . . . . . . [Yamagata307_2009_09_24
. . . . . . . . . . . . . . . . . . . with 123T, syn134G,
. . . . . . . . . . . . . . Moscow_ION_2009_07_16,
. . . . . . . . . . . . . . Bolivia1263_2009_07_14 with syn107Q,
. . . . . . . . . . . . . . Mie41_2009_07_11 with syn107Q]
. . . . . . . . syn366A (GCa) [H5N1],
. . . . . . . . . . . . . . [Unique to PF11 Asia,
. . . . . . . . . . . . . . Netherlands2143_2009_11_16,
. . . . . . . . . . . . . . Maryland31_2009_11_09,
. . . . . . . . . . . . . . Calif_SD35_2009_10_26,
. . . . . . . . . . . . . . NY5297_2009_10_22,
. . . . . . . . . . . . . . NorthCarolina53_2009_10_18,
. . . . . . . . . . . . . . Stockholm67_2009_07_17,
. . . . . . . . . . . . . . MauritusMPn_2009_07_01,
. . . . . . . . . . . . . . MauritusMPt_2009_07_01,
. . . . . . . . . . . . . . ENG92860032_2009_07,
. . . . . . . . . . . . . . ENG520_2009_06,
. . . . . . . . . . . . . . ENG507_2009_06,
. . . . . . . . . . . . . . WiscS1416_2009_10_26_xL (GCt),
. . . . . . . . . . . . . . TexasJMS385_2009_12_04 (GCt)],
. . . . . . . . syn390N [H2, H3N8, H5, H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . . . . . . . [Calif09_2010_05_11,
. . . . . . . . . . . . . . NY7480_2010_03_01,
. . . . . . . . . . . . . . NY03_2010_02_09,
. . . . . . . . . . . . . . Texas01_2010_01_13,
. . . . . . . . . . . . . . TexasJMS400_2009_12_31,
. . . . . . . . . . . . . . TexasJMS399_2009_12_31,
. . . . . . . . . . . . . . TexasJMS398_2009_12_30,
. . . . . . . . . . . . . . TexasJMS397_2009_12_30,
. . . . . . . . . . . . . . Washington73_2009_12_14,
. . . . . . . . . . . . . . NY6937_2009_12_11,
. . . . . . . . . . . . . . Bishkek03_2009_11_28
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S, 175D,
. . . . . . . . . . . . . . Tomsk06_2009_11_22,
. . . . . . . . . . . . . . Russia200_2009_11_01
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S, 175D,
. . . . . . . . . . . . . . NY5196_2009_10_20,
. . . . . . . . . . . . . . NY5141_2009_10_16
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S,
. . . . . . . . . . . . . . ENG94280034_2009_10_06,
. . . . . . . . . . . . . . Texas45093846_2009,
. . . . . . . . . . . . . . Texas45024243_2009,
. . . . . . . . . . . . . . AfghanistanN10786_2009_09_07
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S,
. . . . . . . . . . . . . . AfghanistanN10760_2009_09
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S,
. . . . . . . . . . . . . . AfghanistanN09787_2009_08
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S,
. . . . . . . . . . . . . . Nepal (Nov)
. . . . . . . . . . . . . . NeimengguHuimin11560_2009_12_30,
. . . . . . . . . . . . . . Kentucky16_2009_07_30],
. . . . . . . . syn466G [H5N1, tn],
. . . . . . . . . . . . . . [Unique to PF11 Japan,
. . . . . . . . . . . . . . ChongqingYuzhong11307_2009_12_15
. . . . . . . . . . . . . .. . . . . . . . . . with 219V,
. . . . . . . . . . . . . . NY6864_2009_12_02
. . . . . . . . . . . . . .. . . . . . . . . . with 530I,
. . . . . . . . . . . . . . NY6909_2009_11_29
. . . . . . . . . . . . . .. . . . . . . . . . with 530I,
. . . . . . . . . . . . . . GuangdongHaizhu1644_2009_11_25,
. . . . . . . . . . . . . . NY6675_2009_11_24
. . . . . . . . . . . . . .. . . . . . . . . . with 530I,
. . . . . . . . . . . . . . DC46_2009_11_03
. . . . . . . . . . . . . .. . . . . . . . . . with 530I,
. . . . . . . . . . . . . . NY4995_2009_10_04
. . . . . . . . . . . . . .. . . . . . . . . . with 530I,
. . . . . . . . . . . . . . CalifVRDL75_2009_09_19
. . . . . . . . . . . . . .. . . . . . . . . . with 119M,
. . . . . . . . . . . . . . Texas45130742_2009_09_13,
. . . . . . . . . . . . . .. . . . . . . . . . with syn227E,
. . . . . . . . . . . . . . Texas45132788_2009_09_13,
. . . . . . . . . . . . . . Texas45120922_2009_09_12,
. . . . . . . . . . . . . . Texas45122282_2009_09_12,
. . . . . . . . . . . . . . Texas45113882_2009_09_11],
. . . . . . . . syn548C [H5N1, 1918, tn]
. . . . . . . . . . . . . . [Unique to PF11 Asia,
. . . . . . . . . . . . . . Bishkek03_2009_11_28
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S, 175D,
. . . . . . . . . . . . . . Russia200_2009_11_01
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S, 175D,
. . . . . . . . . . . . . . NY5141_2009_10_16
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S,
. . . . . . . . . . . . . . AfghanistanN10786_2009_09_07
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S,
. . . . . . . . . . . . . . AfghanistanN10760_2009_09
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S,
. . . . . . . . . . . . . . AfghanistanN09787_2009_08
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S])

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

UK Rise in Neuraminidase Inhibitor Anti-Viral Drug Resistance

The UK HPA Weekly National Influenza Reports covering the emerging epidemic from the past two weeks (Week 51 and Week 52) provide insight into data scarcity surrounding anti-viral drug resistance.

Oseltamivir-resistance may be determined genetically from a Single Nucleotide Polymorphism (SNP) H275Y on the Neuraminidase. Clinical anti-viral resistance and / or ineffectiveness in Pandemic H1N1 Influenza continues to manifest much more widely than can be attributed to the genetic variance of NA 275Y.  In the future, other factors may be identified as genetically leading to the clinical manifestations in cases that do not demonstrate H275Y, but for the moment, the measurement is at that single change.

The HPA Week 51 data reported 3 TmX cases from 402 tested (~0.75%).
The HPA Week 52 data reported 5 TmX cases from 336 tested (~1.49%).

As you can see, the percentage of resistant cases week over week increased by 99%.  Unfortunately, data sparsity alongside the fact of taking percentages of percentages may not allow this figure to be fully reliable for decision-making.

On the other hand, in a crisis when faced with limited testing capacity and limited testing foundation, these are the types of acceleration / deceleration calculations that must be made. Data that is available is used. GeneWurx would like to see clinical meta-data paired with genetic sequences to assist in pinpointing various HA polymorphisms that may also be associated with drug resistance, such as those trailing HA aa500.

GeneWurx has prepared an Excel spreadsheet so that the public may track any ongoing official and / or unofficial data concerning Anti-Viral resistance patterns.

GeneWurx_UK_2010_2011_Severe_Wave_TmX_v0.xls

Bear in mind that a recent seasonal influenza rapidly progressed from Anti-Viral sensitivity to Anti-Viral resistance across the world in less than one full season when the percentage of strains demonstrating NA H275Y reached approximately 2%.

More than 100 drug-resistant human Pandemic H1N1 sequences are on file considering just North America and Asia.  Washington01_2010_04_02_TmX from the United States registered with 33 polymorphisms across the HA and NA gene segments.  In August 2010, GeneWurx evaluated 7 sequences from Japan with extensive HA diversity and H275Y TamiFlu Resistance. 

With drug resistant, hypermorphic strains carrying shared HA polymorphisms now being documented across a wide geography, will the resistant 2% begin to spread in Winter 2010-2011?

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