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Commentary - HA 230I on Clade2 TamiFlu Resistant Fatality from Russia

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  • Commentary - HA 230I on Clade2 TamiFlu Resistant Fatality from Russia

    hat tip NS1 -

    2011-10-24

    HA 230I on Clade2 TamiFlu Resistant Fatality from Russia


    Sequences discussed in this analysis are variously stored publicly at GenBank and at GISAID. We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GenBank and from GISAID?s EpiFlu? Database on which this research is based. A GISAID-generated list is detailed in a linked spreadsheet for completeness in citation.

    Last Update
    2011-10-25

    On 2011-10-17, the Central Research Institute for Epidemiology under the Federal Budget Institute of Science (Moscow, Russia) released a series of human pH1N1 sequences at GenBank and GISAID with no specified subject age or gender. The samples cover 7 distinct geographic areas spanning 2010-12-31 to 2011-03-14 with the largest group in January 2010 and demonstrate avian influence.

    HA 253 Total Polymorphisms Averaging ~11.0 per Segment
    NA 142 Total Polymorphisms Averaging ~6.2 per Segment

    HA and NA Total 395 Polymorphisms Averaging ~17.2 per Sequence

    Of the 23 sequences, Clade2: 188T is predominant with 20 enlistments. Clade4: 128D and Clade5: 208K_219V are respectively represented with 1 and 2 entries. 5 sequences carry polymorphisms at the critical Receptor Binding Site aa225, including the fatality markers of 225G and 225N. 9 of the sequences (all Moscow Oblast) carry HA 73F, an Asian marker that is rare to European pH1N1 and domains near the emergent HA 77N. 10 sequences from the Russian deposit are fatalities, isolated from ?lung autopsy tissue?. The fatalities sequence primarily onto Clade2: 188T (9 sequences) with 1 fatality falling on Clade4: 128D. TamiFlu Resistance is genetically indicated with NA 275Y on 2 sequences, both Clade2: 188T fatalities.

    One fatal sequence, RussiaNizhniiNovgorodCRIE_BLM_L_2011_01_26_TmX_f, carries the HA 230I paired with an emergent 77N, similar to the previous regional HA 230I-bearing sequence, RussiaBelgorod2_2010_03_15. The Nizhnii Novgorod HA 230I (ATt) becomes the second coding of Isoleucine at aa230 on a Clade2: 188T background after SwedenHalmstad1_23F_2010_12_21 coded as ATa. The TamiFlu Resistant Nizhnii Novgorod sequence is hypermorphic with 10 revisions each on the HA and NA gene segments for a total of 20 revisions. The Clade2 underpinning is commonly circulating, but has 3 uncommon additions: 77N, 142V and 230I.

    . . . . RussiaStPeterCRIE_GoVM_L_2011_03_14_TmX_f (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339343
    . . . . . . . . 11 Polymorphisms (6 Amino and 5 Silent)
    . . . . . . . . 100N,
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . 225G,
    . . . . . . . . 286N,
    . . . . . . . . syn332L (tTA),
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn542S (TCc))

    . . . . RussiaStPeterCRIE_GoVM_L_2011_03_14_TmX_f (
    . . . . . . . . GISAID NA EPI339344
    . . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
    . . . . . . . . 11S,
    . . . . . . . . syn86A (GCt),
    . . . . . . . . 222K,
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 275Y,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaJoshkarOlaCRIE_BLP_L_2011_02_22_f (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339328
    . . . . . . . . 16 Polymorphisms (8 Amino and 8 Silent)
    . . . . . . . . syn10Y (TAc),
    . . . . . . . . syn34N (AAt),
    . . . . . . . . syn118E (GAa),
    . . . . . . . . 146G,
    . . . . . . . . 188T,
    . . . . . . . . 200T,
    . . . . . . . . 225G mix wt,
    . . . . . . . . 225N mix wt,
    . . . . . . . . 225S mix wt,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . syn358N (AAc) [H1N1 Avian],
    . . . . . . . . 377K,
    . . . . . . . . syn418F (TTt),
    . . . . . . . . 454N,
    . . . . . . . . syn465N (AAt),
    . . . . . . . . syn542S (TCc))

    . . . . RussiaJoshkarOlaCRIE_BLP_L_2011_02_22_f (
    . . . . . . . . GISAID NA EPI339330
    . . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
    . . . . . . . . 44S,
    . . . . . . . . syn140L (tTA) mix wt,
    . . . . . . . . syn206L (cTA) [H1N1 Avian Farm],
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa))

    . . . . RussiaTulaCRIE_STA_2011_02_11 (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339347
    . . . . . . . . 12 Polymorphisms (5 Amino and 7 Silent)
    . . . . . . . . syn15S (TCg),
    . . . . . . . . syn39K (AAa),
    . . . . . . . . syn69E (GAa),
    . . . . . . . . 100N,
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . 442V mix wt,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn542S (TCc))

    . . . . RussiaTulaCRIE_STA_2011_02_11 (
    . . . . . . . . GISAID NA EPI339348
    . . . . . . . . 9 Polymorphisms (3 Amino and 6 Silent)
    . . . . . . . . syn18G (GGg),
    . . . . . . . . syn177V (GTa),
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . 386S,
    . . . . . . . . syn410P (CCt),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaTulaCRIE_GSYu_2011_02_08 (
    . . . . . . . . Clade5: 208K_219V
    . . . . . . . . GISAID HA EPI339349
    . . . . . . . . 13 Polymorphisms (6 Amino and 7 Silent)
    . . . . . . . . syn36L (tTA),
    . . . . . . . . syn47L (CTg),
    . . . . . . . . 100N,
    . . . . . . . . syn102E (GAa),
    . . . . . . . . syn161Y (TAt),
    . . . . . . . . syn170N (AAc),
    . . . . . . . . 208K,
    . . . . . . . . 219V,
    . . . . . . . . 252L,
    . . . . . . . . 359G,
    . . . . . . . . 377K,
    . . . . . . . . syn446K (AAa),
    . . . . . . . . syn542S (TCc))

    . . . . RussiaTulaCRIE_GSYu_2011_02_08 (
    . . . . . . . . GISAID NA EPI339350
    . . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
    . . . . . . . . syn18G (GGg),
    . . . . . . . . syn138A (GCt),
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa))

    . . . . RussiaVolgogradCRIE_DMV_L_2011_02_05_f (
    . . . . . . . . Clade4: 128D
    . . . . . . . . GISAID HA EPI339336
    . . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
    . . . . . . . . syn60I (ATc) [H9N2 Human and Avian Emergent],
    . . . . . . . . . . . . . . . . [1918],
    . . . . . . . . 128D,
    . . . . . . . . 225G,
    . . . . . . . . 377K,
    . . . . . . . . syn392Q (CAa) [H1N1 Avian wt],
    . . . . . . . . syn469E (GAg) [pH1N1 Upsilon
    . . . . . . . . . . . . . . . . . . . . . Estonia55236_30M_2011_03_02
    . . . . . . . . . . . . . . . . . . . . . . . . with 42W, syn87S and 397G,
    . . . . . . . . . . . . . . . . . . . . . Denmark111_2010_12_07
    . . . . . . . . . . . . . . . . . . . . . . . . with syn87S and 397G]
    . . . . . . . . . . . . . . . . . . [pH1N1 Australia VxX with 128D],
    . . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010],
    . . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
    . . . . . . . . . . . . . . . . . . [H5N1 Azerbaijan Human 2006],
    . . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
    . . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
    . . . . . . . . . . . . . . . . . . [H5N1 Feline with syn40H, syn55L],
    . . . . . . . . . . . . . . . . . . [H5N2 Avian],
    . . . . . . . . . . . . . . . . . . [H9N2 Avian wt],
    . . . . . . . . . . . . . . . . . . [H9N2 Human with 39E, syn40H, syn42G],
    . . . . . . . . . . . . . . . . . . [H1N1 Avian tn],
    . . . . . . . . . . . . . . . . . . [H1N1 Swine],
    . . . . . . . . . . . . . . . . . . [1918],
    . . . . . . . . . . . . . . . . . . [H1N2 Swine],
    . . . . . . . . syn542S (TCc))

    . . . . RussiaVolgogradCRIE_DMV_L_2011_02_05_f (
    . . . . . . . . GISAID NA EPI339338
    . . . . . . . . 8 Polymorphisms (6 Amino and 2 Silent)
    . . . . . . . . 78H,
    . . . . . . . . 249E,
    . . . . . . . . 264I,
    . . . . . . . . syn327R (CGt),
    . . . . . . . . syn339S (TCa),
    . . . . . . . . 359V,
    . . . . . . . . 397K,
    . . . . . . . . 442I)

    . . . . RussiaTulaCRIE_SYuP_2011_02_04 (
    . . . . . . . . Clade5: 208K_219V
    . . . . . . . . GISAID HA EPI339351
    . . . . . . . . 15 Polymorphisms (7 Amino and 8 Silent)
    . . . . . . . . syn36L (tTA),
    . . . . . . . . syn47L (CTg),
    . . . . . . . . 100N,
    . . . . . . . . syn102E (GAa),
    . . . . . . . . syn161Y (TAt),
    . . . . . . . . syn170N (AAc),
    . . . . . . . . 208K,
    . . . . . . . . 219V,
    . . . . . . . . 252L,
    . . . . . . . . 359G,
    . . . . . . . . 377K,
    . . . . . . . . 397D mix wt,
    . . . . . . . . syn446K (AAa),
    . . . . . . . . syn533L (tTG) mix wt,
    . . . . . . . . syn542S (TCc))

    . . . . RussiaTulaCRIE_SYuP_2011_02_04 (
    . . . . . . . . GISAID NA EPI339352
    . . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
    . . . . . . . . syn18G (GGg),
    . . . . . . . . syn138A (GCt),
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa))

    . . . . RussiaArchangelskCRIE_PE_2011_02_01 (
    . . . . . . . . Clade2: 188T with H5N1 Homology
    . . . . . . . . GISAID HA EPI339345
    . . . . . . . . 14 Polymorphisms (5 Amino and 9 Silent)
    . . . . . . . . syn34N (AAt),
    . . . . . . . . syn122K (AAa),
    . . . . . . . . 146G,
    . . . . . . . . 188T,
    . . . . . . . . 200T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . syn376D (GAt) [H2, H3N8, H4],
    . . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
    . . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2008-2010],
    . . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine],
    . . . . . . . . . . . . . . . . . . [H6, H7N3, H7N7, H9N2, H11],
    . . . . . . . . 377K,
    . . . . . . . . syn379T (ACc) [H5N1 Egypt Human Gharbiyah, 80% CFR],
    . . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2008-2010],
    . . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine],
    . . . . . . . . . . . . . . . . . . [H5N1 North America Avian],
    . . . . . . . . . . . . . . . . . . [H1N1 Europe Avian 2010
    . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
    . . . . . . . . syn425N (AAc) [H1N1 Avian Farm
    . . . . . . . . . . . . . . . . . . . . . . . . with syn376D
    . . . . . . . . . . . . . . . . . . . . . . . . . . . & extensive pH1N1υ polymorphisms],
    . . . . . . . . 454N,
    . . . . . . . . syn465N (AAt),
    . . . . . . . . syn538F (TTt),
    . . . . . . . . syn542S (TCc))

    . . . . RussiaArchangelskCRIE_PE_2011_02_01 (
    . . . . . . . . GISAID NA EPI339346
    . . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
    . . . . . . . . syn38I (ATc),
    . . . . . . . . 44S,
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 264I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa))

    . . . . RussiaMoscowOblastCRIE_HDV_2011_01_28 (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339355
    . . . . . . . . 11 Polymorphisms (6 Amino and 5 Silent)
    . . . . . . . . 73F (tTC) [H1N1 Avian (tTa, tTg)],
    . . . . . . . . . . . . . . . [H9N2 Avian Emergent (tTg)],
    . . . . . . . . 100N,
    . . . . . . . . 124N [Emergent on pH1N1 Clade 1 (189T)
    . . . . . . . . . . . . . . . . with 77N, 233H, 275A],
    . . . . . . . . . . . [H5N1 Avian, Human and Equine],
    . . . . . . . . . . . [H1N1 Avian
    . . . . . . . . . . . . . . . . with syn42G, 189T, syn346G, 453K],
    . . . . . . . . . . . [H3N2 Human Emergent],
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn478C (TGt),
    . . . . . . . . syn542S (TCc))

    . . . . RussiaMoscowOblastCRIE_HDV_2011_01_28 (
    . . . . . . . . GISAID NA EPI339356
    . . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 353H mix wt,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaMoscowOblastCRIE_LNR_2011_01_28 (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339371
    . . . . . . . . 11 Polymorphisms (6 Amino and 5 Silent)
    . . . . . . . . 73F (tTC) [H1N1 Avian (tTa, tTg)],
    . . . . . . . . . . . . . . . [H9N2 Avian Emergent (tTg)],
    . . . . . . . . 100N,
    . . . . . . . . 124N [Emergent on pH1N1 Clade 1 (189T)
    . . . . . . . . . . . . . . . . with 77N, 233H, 275A],
    . . . . . . . . . . . [H5N1 Avian, Human and Equine],
    . . . . . . . . . . . [H1N1 Avian
    . . . . . . . . . . . . . . . . with syn42G, 189T, syn346G, 453K],
    . . . . . . . . . . . [H3N2 Human Emergent],
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn478C (TGt),
    . . . . . . . . syn542S (TCc))

    . . . . RussiaMoscowOblastCRIE_LNR_2011_01_28 (
    . . . . . . . . GISAID NA EPI339372
    . . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaMoscowOblastCRIE_VFE_2011_01_28 (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339373
    . . . . . . . . 11 Polymorphisms (6 Amino and 5 Silent)
    . . . . . . . . 73F (tTC) [H1N1 Avian (tTa, tTg)],
    . . . . . . . . . . . . . . . [H9N2 Avian Emergent (tTg)],
    . . . . . . . . 100N,
    . . . . . . . . 124N [Emergent on pH1N1 Clade 1 (189T)
    . . . . . . . . . . . . . . . . with 77N, 233H, 275A],
    . . . . . . . . . . . [H5N1 Avian, Human and Equine],
    . . . . . . . . . . . [H1N1 Avian
    . . . . . . . . . . . . . . . . with syn42G, 189T, syn346G, 453K],
    . . . . . . . . . . . [H3N2 Human Emergent],
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn478C (TGt),
    . . . . . . . . syn542S (TCc))

    . . . . RussiaMoscowOblastCRIE_VFE_2011_01_28 (
    . . . . . . . . GISAID NA EPI339374
    . . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaMoscowOblastCRIE_7_2011_01_27 (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339377
    . . . . . . . . 11 Polymorphisms (6 Amino and 5 Silent)
    . . . . . . . . 73F (tTC) [H1N1 Avian (tTa, tTg)],
    . . . . . . . . . . . . . . . [H9N2 Avian Emergent (tTg)],
    . . . . . . . . 100N,
    . . . . . . . . 124N [Emergent on pH1N1 Clade 1 (189T)
    . . . . . . . . . . . . . . . . with 77N, 233H, 275A],
    . . . . . . . . . . . [H5N1 Avian, Human and Equine],
    . . . . . . . . . . . [H1N1 Avian
    . . . . . . . . . . . . . . . . with syn42G, 189T, syn346G, 453K],
    . . . . . . . . . . . [H3N2 Human Emergent],
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn478C (TGt),
    . . . . . . . . syn542S (TCc))

    . . . . RussiaMoscowOblastCRIE_7_2011_01_27 (
    . . . . . . . . GISAID NA EPI339378
    . . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaMoscowOblastCRIE_6_2011_01_27 (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339375
    . . . . . . . . 11 Polymorphisms (6 Amino and 5 Silent)
    . . . . . . . . 73F (tTC) [H1N1 Avian (tTa, tTg)],
    . . . . . . . . . . . . . . . [H9N2 Avian Emergent (tTg)],
    . . . . . . . . 100N,
    . . . . . . . . 124N [Emergent on pH1N1 Clade 1 (189T)
    . . . . . . . . . . . . . . . . with 77N, 233H, 275A],
    . . . . . . . . . . . [H5N1 Avian, Human and Equine],
    . . . . . . . . . . . [H1N1 Avian
    . . . . . . . . . . . . . . . . with syn42G, 189T, syn346G, 453K],
    . . . . . . . . . . . [H3N2 Human Emergent],
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn478C (TGt),
    . . . . . . . . syn542S (TCc))

    . . . . RussiaMoscowOblastCRIE_6_2011_01_27 (
    . . . . . . . . GISAID NA EPI339376
    . . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaNizhniiNovgorodCRIE_BLM_L_2011_01_26_TmX_f (
    . . . . . . . . Clade2: 188T with 142V & 230I
    . . . . . . . . GISAID HA EPI339320
    . . . . . . . . 10 Polymorphisms (7 Amino and 3 Silent)
    . . . . . . . . 77N [Recently Novel to Clade1.Upsilon],
    . . . . . . . . . . . . [Emergent on pH1N1 Clade 1 (189T)
    . . . . . . . . . . . . . . . . with 124N, 233H, 275A],
    . . . . . . . . . . . . [H1N1 Avian
    . . . . . . . . . . . . . . . . with syn42G, 159T,
    . . . . . . . . . . . . . . . . . . . . 188T, 189T, syn346G, 453K],
    . . . . . . . . . . . . [Rare to H1N1 US Swine with 124N (6)],
    . . . . . . . . 100N,
    . . . . . . . . 142V (GtT) [H5N1 Avian (atg, ctt, ctg, ttg)],
    . . . . . . . . 188T,
    . . . . . . . . 230I (ATt) [H9N2 Avian & Human wt],
    . . . . . . . . . . . . [H10N7 Avian 2008
    . . . . . . . . . . . . . . . . with #1V, 87N, syn94Y, 100N, syn102E,
    . . . . . . . . . . . . . . . . . . . 156E, 157E, 163T, 165N,
    . . . . . . . . . . . . . . . . . . . syn177L, 188T, syn221P, syn207S, syn213F,
    . . . . . . . . . . . . . . . . . . . 225G, 230I, 233H, 237I, syn239P,
    . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn356H,
    . . . . . . . . . . . . . . . . . . . syn390N, syn391T],
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . 454N,
    . . . . . . . . syn474C (TGt) [H2 2009],
    . . . . . . . . . . . . . . . . . . [H3N8 Canine 2007, Equine 2009, Swine],
    . . . . . . . . . . . . . . . . . . [H5N1 wt],
    . . . . . . . . . . . . . . . . . . [H5N2 Avian],
    . . . . . . . . . . . . . . . . . . [H9N2 2009],
    . . . . . . . . . . . . . . . . . . [H1N1 Avian 2010],
    . . . . . . . . . . . . . . . . . . [H1N1 swine 2010],
    . . . . . . . . syn542S (TCc) [H2, H5, H9N2],
    . . . . . . . . . . . . . . . . . . [H1N1 Avian Farm
    . . . . . . . . . . . . . . . . . . . . . with pH1N1υ polymorphisms])

    . . . . RussiaNizhniiNovgorodCRIE_BLM_L_2011_01_26_TmX_f (
    . . . . . . . . GISAID NA EPI339322
    . . . . . . . . 10 Polymorphisms (4 Amino and 6 Silent)
    . . . . . . . . syn51Q (CAg) [H1N1 Avian
    . . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
    . . . . . . . . 76S [H1N1 Avian
    . . . . . . . . . . . . . . with syn240T, 241I],
    . . . . . . . . syn111K (AAa) [H1N1 Avian Farm],
    . . . . . . . . syn204A (GCa),
    . . . . . . . . syn240T (ACc) [H1N1 Avian Farm],
    . . . . . . . . 241I [H1N1 Avian Farm],
    . . . . . . . . 275Y mix wt,
    . . . . . . . . 369K [H1N1 Avian
    . . . . . . . . . . . . . . . . with syn111K, syn240T, 241I],
    . . . . . . . . syn377P (CCa) [H5N1 Avian],
    . . . . . . . . . . . . . . . . . . . [H1N1 Avian
    . . . . . . . . . . . . . . . . . . . . . . with 241I],
    . . . . . . . . . . . . . . . . . . . [H1N1 Avian
    . . . . . . . . . . . . . . . . . . . . . . exclusive of syn240T (ACc)],
    . . . . . . . . syn416D (GAc) [H5N1 Avian Emergent 2011],
    . . . . . . . . . . . . . . . . . . . [H1N1 Avian
    . . . . . . . . . . . . . . . . . . . . . . with syn51Q, syn240T, 241I],
    . . . . . . . . . . . . . . . . . . . [H1N1 Avian
    . . . . . . . . . . . . . . . . . . . . . . with syn111K, syn377P])

    . . . . RussiaMoscowOblastCRIE_135_2011_01_25 (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339365
    . . . . . . . . 11 Polymorphisms (6 Amino and 5 Silent)
    . . . . . . . . 73F (tTC) [H1N1 Avian (tTa, tTg)],
    . . . . . . . . . . . . . . . [H9N2 Avian Emergent (tTg)],
    . . . . . . . . 100N,
    . . . . . . . . 124N [Emergent on pH1N1 Clade 1 (189T)
    . . . . . . . . . . . . . . . . with 77N, 233H, 275A],
    . . . . . . . . . . . [H5N1 Avian, Human and Equine],
    . . . . . . . . . . . [H1N1 Avian
    . . . . . . . . . . . . . . . . with syn42G, 189T, syn346G, 453K],
    . . . . . . . . . . . [H3N2 Human Emergent],
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn478C (TGt),
    . . . . . . . . syn542S (TCc))

    . . . . RussiaMoscowOblastCRIE_135_2011_01_25 (
    . . . . . . . . GISAID NA EPI339366
    . . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaMoscowOblastCRIE_134_2011_01_25 (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339363
    . . . . . . . . 11 Polymorphisms (6 Amino and 5 Silent)
    . . . . . . . . 73F (tTC) [H1N1 Avian (tTa, tTg)],
    . . . . . . . . . . . . . . . [H9N2 Avian Emergent (tTg)],
    . . . . . . . . 100N,
    . . . . . . . . 124N [Emergent on pH1N1 Clade 1 (189T)
    . . . . . . . . . . . . . . . . with 77N, 233H, 275A],
    . . . . . . . . . . . [H5N1 Avian, Human and Equine],
    . . . . . . . . . . . [H1N1 Avian
    . . . . . . . . . . . . . . . . with syn42G, 189T, syn346G, 453K],
    . . . . . . . . . . . [H3N2 Human Emergent],
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn478C (TGt),
    . . . . . . . . syn542S (TCc))

    . . . . RussiaMoscowOblastCRIE_134_2011_01_25 (
    . . . . . . . . GISAID NA EPI339364
    . . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaMoscowOblastCRIE_132_2011_01_25 (
    . . . . . . . . GISAID HA EPI339369
    . . . . . . . . 11 Polymorphisms (6 Amino and 5 Silent)
    . . . . . . . . 73F (tTC) [H1N1 Avian (tTa, tTg)],
    . . . . . . . . . . . . . . . [H9N2 Avian Emergent (tTg)],
    . . . . . . . . 100N,
    . . . . . . . . 124N [Emergent on pH1N1 Clade 1 (189T)
    . . . . . . . . . . . . . . . . with 77N, 233H, 275A],
    . . . . . . . . . . . [H5N1 Avian, Human and Equine],
    . . . . . . . . . . . [H1N1 Avian
    . . . . . . . . . . . . . . . . with syn42G, 189T, syn346G, 453K],
    . . . . . . . . . . . [H3N2 Human Emergent],
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn478C (TGt),
    . . . . . . . . syn542S (TCc))

    . . . . RussiaMoscowOblastCRIE_131_2011_01_25 (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339367
    . . . . . . . . 11 Polymorphisms (6 Amino and 5 Silent)
    . . . . . . . . 73F (tTC) [H1N1 Avian (tTa, tTg)],
    . . . . . . . . . . . . . . . [H9N2 Avian Emergent (tTg)],
    . . . . . . . . 100N,
    . . . . . . . . 124N [Emergent on pH1N1 Clade 1 (189T)
    . . . . . . . . . . . . . . . . with 77N, 233H, 275A],
    . . . . . . . . . . . [H5N1 Avian, Human and Equine],
    . . . . . . . . . . . [H1N1 Avian
    . . . . . . . . . . . . . . . . with syn42G, 189T, syn346G, 453K],
    . . . . . . . . . . . [H3N2 Human Emergent],
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn478C (TGt),
    . . . . . . . . syn542S (TCc))

    . . . . RussiaMoscowOblastCRIE_131_2011_01_25 (
    . . . . . . . . GISAID NA EPI339368
    . . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaNizhniiNovgorodCRIE_KDA_L_2011_01_24_f (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339353
    . . . . . . . . 10 Polymorphisms (6 Amino and 4 Silent)
    . . . . . . . . 100N,
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . 225N mix wt,
    . . . . . . . . 280A,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn542S (TCc))

    . . . . RussiaNizhniiNovgorodCRIE_KDA_L_2011_01_24_f (
    . . . . . . . . GISAID NA EPI339354
    . . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
    . . . . . . . . 59K,
    . . . . . . . . syn177V (GTa),
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaNizhniiNovgorodCRIE_BOU_L_2011_01_21_f (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339359
    . . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
    . . . . . . . . 100N,
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn542S (TCc))

    . . . . RussiaNizhniiNovgorodCRIE_BOU_L_2011_01_21_f (
    . . . . . . . . GISAID NA EPI339360
    . . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
    . . . . . . . . syn177V (GTa),
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaNizhniiNovgorodCRIE_CEN_L_2011_01_19_f (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339357
    . . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
    . . . . . . . . 100N,
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn542S (TCc))

    . . . . RussiaNizhniiNovgorodCRIE_CEN_L_2011_01_19_f (
    . . . . . . . . GISAID NA EPI339358
    . . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
    . . . . . . . . syn177V (GTa),
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaNizhniiNovgorodCRIE_PAV_L_2011_01_10_f (
    . . . . . . . . Clade2: 188T with 142V
    . . . . . . . . GISAID HA EPI339341
    . . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
    . . . . . . . . 100N,
    . . . . . . . . 142V (GtT) [H5N1 Avian (atg, ctt, ctg, ttg)],
    . . . . . . . . 188T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . 454N,
    . . . . . . . . syn474C (TGt),
    . . . . . . . . syn542S (TCc))

    . . . . RussiaNizhniiNovgorodCRIE_PAV_L_2011_01_10_f (
    . . . . . . . . GISAID NA EPI339342
    . . . . . . . . 10 Polymorphisms (5 Amino and 5 Silent)
    . . . . . . . . syn51Q (CAg),
    . . . . . . . . 76S,
    . . . . . . . . 115L,
    . . . . . . . . syn204A (GCa),
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 322L [H1N1 Avian with syn240T, 241I],
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaNizhniiNovgorodCRIE_ZCA_L_2011_01_02_f (
    . . . . . . . . Clade2: 188T
    . . . . . . . . GISAID HA EPI339361
    . . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
    . . . . . . . . 100N,
    . . . . . . . . syn179L (CTg),
    . . . . . . . . 188T,
    . . . . . . . . 225N,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . syn448L (TTg),
    . . . . . . . . 454N,
    . . . . . . . . syn542S (TCc))

    . . . . RussiaNizhniiNovgorodCRIE_ZCA_L_2011_01_02_f (
    . . . . . . . . GISAID NA EPI339362
    . . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
    . . . . . . . . syn177V (GTa),
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))

    . . . . RussiaNizhniiNovgorodCRIE_NGV_L_2010_12_31_f (
    . . . . . . . . Clade2: 188T with 142V
    . . . . . . . . GISAID HA EPI339312
    . . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
    . . . . . . . . 100N,
    . . . . . . . . 142V (GtT) [H5N1 Avian (atg, ctt, ctg, ttg)],
    . . . . . . . . 188T,
    . . . . . . . . syn338G (GGc),
    . . . . . . . . 377K,
    . . . . . . . . 454N,
    . . . . . . . . syn474C (TGt),
    . . . . . . . . syn542S (TCc))

    . . . . RussiaNizhniiNovgorodCRIE_NGV_L_2010_12_31_f (
    . . . . . . . . GISAID NA EPI339314
    . . . . . . . . 9 Polymorphisms (4 Amino and 5 Silent)
    . . . . . . . . syn51Q (CAg),
    . . . . . . . . 76S,
    . . . . . . . . 115L,
    . . . . . . . . syn204A (GCa),
    . . . . . . . . syn240T (ACc),
    . . . . . . . . 241I,
    . . . . . . . . 369K,
    . . . . . . . . syn377P (CCa),
    . . . . . . . . syn416D (GAc))



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