2010-11-22

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

Last Updated
2011-02-09

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

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

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

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

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

Age Factor and Mechanism Hypothesis

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

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

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

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

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

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

230I Additions

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

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

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

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

Prediction
Prediction Validation

Supporting Sequences

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

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

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

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

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

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

Related Sequences

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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







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