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

Last Updated
2011-02-09

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

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

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

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

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

Age Factor and Mechanism Hypothesis

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

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

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

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

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

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

230I Additions

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

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

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

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

Prediction

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

Prediction Validation

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

Supporting Sequences

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

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

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

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

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

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

Related Sequences

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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228R from Iran Increases Critical Receptor Binding Domain Diversity Above 90%

Last Updated 2010-10-26

In positions where this flu is revising the pandemic gene code, the ΣPF11 reservoir (pH1N1) presently exhibits a strong pattern of alliance with serotypes normally infecting birds, horses and dogs.

100% of the Hemagglutinin positions between 186 and 248, including antigenic areas of the Receptor Binding Domain (RBD/RBS), are on record as polymorphic. No position in that range is stable.  Many positions rate multiple changes.  Protein revision is now documented at 57 of the 63 positions (90%), engaging the potential for antibody resistance (natural immune escape and vaccine escape). 

The Shiraz University of Medical Science released a group of sequences today at GenBank.  Each demonstrates unusual characteristics.  One stands above the others.  IranShiraz1_2010_02 carries a previously unseen Receptor Binding Domain revision, 228R, alongside changes found recently in the H10N7 reservoir. Of interest is the fact that changes at or around amino acid position 238 and changes at or around 275 are associated with an emerging sub-clade that is permissive to and demonstrates the M230I polymorphism.

Is 228R another tertiary Immune Escape marker similar in mechanism to 230I?  Iran has also documented 227Q in the reservoir on a hyper-morphic sample, Iran15583_2009_11_21.

. . . . IranShiraz1_2010_02 (
. . . . . . . . 88T,
. . . . . . . . 90K,
. . . . . . . . 91W,
. . . . . . . . syn218A [WSN33],
. . . . . . . . . . . . . . . [Nebraska02_2010_03_11
. . . . . . . . . . . . . . . . . . . . . .with 523A,
. . . . . . . . . . . . . . . CubaHabana2687_2009
. . . . . . . . . . . . . . . . . . . . . .with 221T]
. . . . . . . . 228R (cGG) [H9N2 2008 (AGA)],
. . . . . . . . 238Q [H10N7 2009],
. . . . . . . . 246Q,
. . . . . . . . 277N [H5N1, H10N7 2009],
. . . . . . . . . . . . . [Iran15583_2009_11_21,
. . . . . . . . . . . . . Wisconsin],
. . . . . . . . syn350G [swThaiCURA4_2009_11
. . . . . . . . . . . . . . . . . . . with 226R, syn484N])

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HA 230I Receptor Binding Domain Polymorphism Potential for Spread

Current trending indicates a reportable potential for the M230I polymorphism spreading on the Hemagglutinin of PF11. This Receptor Binding Domain change may enhance Vaccine Escape from the currently selected vaccine target candidate, CA/07 X181. 

For those who are following the prediction on February 25, 2010, the pandemic reservoir now shows multiple instances of multiple encodings for 230I. 

The 230I bearing sequences meeting the prediction are documented in the detailed discussion on Vaccine Escape that demonstrates a 100% change rate in the pandemic influenza (pH1N1) reservoir at the critical HA genetics range between amino acid positions 186 and 248.  87% of the amino acid positions have notated revisions.

Expectations for the M230I polymorphism, that first came to our notice for zoonotic concern on the H5N1 human fatality cluster, have now been revised based on the most current public data.

• 45% probability in Arizona of HA 230I in PF11 RBS within 60 days.
• 75% probability in Arizona of HA 230I in PF11 RBS within 210 days.

• 75% probability of HA 230I in PF11 RBS within 90 days in one of:
• Arizona, Utah, Nevada
• California
• Texas
• New York
• Wisconsin (spread)
• Minnesota (spread)
• Japan (spread)
• Greece
• Russia
• Ukraine
• 87% probability of HA 230I in PF11 RBS within 210 days in one of:
• Arizona, Utah, Nevada
• California
• Texas
• New York
• Wisconsin (spread)
• Minnesota (spread)
• Hawaii
• Delaware
• Vermont
• Iowa
• Kentucky
• Japan (spread)
• Greece
• Russia
• Ukraine

• 5% or less probability of HA 230I within 60 days of conserving across PF11.
• 7% probability of HA 230I within 210 days of conserving on one or more Hydrae.

Anti-viral drug usage may drive 230I genetic acquisition.

The following geographies show potential to acquire the HA polymorphism in an anti-viral over-usage climate.  Anti-viral resistance from the NA H275Y revision is not the only genetic concern with over-usage.  We suggest that the rate of adoption will vary by penetration percentage of anti-viral implementation techniques geared toward sub-clinical symptomology and pre-emptively medicating undiagnosed contacts ("blanket") with Neuraminidase Inhibitors.

• 35% to 50% probability of HA 230I in PF11 RBS within 90 days in one of:
• Georgia
• South Carolina
• North Carolina

These probabilities will be updated as additional data is made public.  Transparency at this stage of the pandemic is essential.  Release of sequences and clinical data of a finer detail and higher quantity will allow information-based decisions.

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90% Change Rate on Unstable HA Antigen Range with H9N2 and H5N1 Bird Flu Matches

A recent slight increase in data transparency has allowed a higher quality documentation of the actual change rate for the HA within the ΣPF11 reservoir.  Though hundreds of sequences are being deposited with substantial truncations in important areas, we work with the data that is surfaced and ask for the portions that have been withheld.  Considering the limited availability of raw data, the analyses continue to yield patterns and ratios worthy of report.

More than 90% of the Hemagglutinin positions between 186 and 246, including antigenic areas of the Receptor Binding Domain (RBD/RBS), are on record as polymorphic. Only 6 positions in that range are stable.  Many positions rate multiple changes. The list presented today is certainly not comprehensive. For the sake of brevity, only one section is discussed from one gene segment (HA) covering 61 contiguous amino acid positions. The extensive variation in that short range is documented in the trailing data.

Of course, viral revision is also rapidly occurring in additional HA antigenic areas outside the range of positions documented in this analysis.  The Neuraminidase of the human pandemic H1N1 reservoir is acquiring revisions with homology to Avian and Equine influenza at a ratio even higher than that of the Hemagglutinin being surveyed in this analysis.

The viral reservoir backing this present H1N1 pandemic is far from stable and is actively acquiring new genetics. Current data does not indicate an immediate direction toward stability.

A previous version of this listing may be referenced for tracking.  There you will find details on the causality behind this particular study. 

186S synonymous (TCc) Russia61, BZSP53823_2009_08_01_f,
. . . . BadenWurttemberg8_2010, TexasJMS387_2009_12_08,
. . . . KO_Daegu1873_2009_12_16_TmX,
. . . . H9N2 (cCc, cac)
186P (cCT) CalifVRDL7, UkraineChernihiv857, Ankara17
. . . . Thessaloniki791_2010 mix (225G, syn233Y, 324I, 377K)
186F (TtT) Ankara26
187T synonymous (ACc) Berlin164, Iran572, BeijingXicheng11649,
. . . . S5, 1918, H9N2
187A (gCT) TexasJMS405_2009, TexasJMS406_2009,
. . . . H5 (gaT)
188T (AcT) swThaiCURA75_2010_01,
. . . . H6N1 dkHK202_1977, dkKOS17_2003,
. . . . H7N7 extensive including human fatality
188S synonymous (AGc) NY6943_xL
188N SC16, SC31, NY3502, ME15, CatS1187, Milan433, Kaifu4142,
. . . . Bilthoven4360903023, Japan, China,
. . . . swHK_NS1809_2009_12_03 (189T), swHK_NS1810_2009_12_03
. . . . S5, H5
188I Growing in US on cross-linked background (4), BZSP53823 (186S),
. . . . H1N1 (1943, 46, 51)
189V Sydney2503, Texas46172731,
. . . . Sask, H6N1 mallMaryland887_2002
189S Wisc1434
189T Extensive in US incl NY7020 (77N), on cross-linkage (4) incl
. . . . NY6943_xL, Ontario328474, Aswan2288, China,
. . . . swHK_NS1809_2009_12_03 (188N)
. . . . H5N1 2009, H6N1, H9N2 2008
189A synonymous (GCc), Georgia01_2010, Georgia 2010 (+5), swOR4060
190D synonymous (GAt) Nebraska02_2010, Milan326, UkraineZakarpatska830,
. . . . AfghanN09833_2009_08
. . . . 1918, H1N1 (1943, 51)
190Y SwedenMalmoe1_2010_01_01, H6N1 (tTG)
191R (CgA) Chengdu18 (131P), GuangdongSWL28 (192H, 199N)
192H (CAt) GuangdongSWL28 (191R, 199N)
. . . . H2N3 (agt), H3N8 (act), H6N1 (aAt, gat, gct)
192Q synonymous (CAg) RomaISS50 (227V), Nebraska01_2010, H1N1 (1943, 46)
193S synonymous (AGc) SC18, US 2010 (4), Milan294, Japan,
. . . . AfghanN10765_2009_09
. . . . H3N8 AGc aplatBelgium12827_2007,
. . . . H6N1 AGc chkTaiwan0706_2003,
. . . . H9N2 Aac dkViet2009,
. . . . H11Nx Aac dkViet2009
193G (gGT) AR08, Cal_SDINS04, Kansas26,
. . . . H5N1 (gGg), H3N8 (gaT, gac, gaa), H11 (gac, gat)
193N (AaT) Washington72, H3N8, H6N1, H9N2, H11
193R (cGT) catItaly304678_1_2009_12_17_f, Origin Unknown
194I  (aTC) NC38E3, VA27, SC18, Bangladesh3009, StPete59, StPete99,
. . . . Thessaloniki788_2010 (syn233Y, 324I, 377K),
. . . . China (3),
. . . . H5N1
194L synonymous (CTa) Japan4081, tn
. . . . H9N2 2008 (tTa), H6N1 chkTaiwan1205_2001 (CTa)
194L synonymous (CTt) TexasJMS385_2009, CalifVRDL36,
. . . . EgyptN11640_2009_10, Iran572,
. . . . H9N2 dkVietnamOIE2327_2009
196Q synonymous (CAa) Wisc (3), Moldova (3), Malaysia (2), China,
. . . . Milan326, Pavia (6), Ankara18, NordrheinWestfalen106, swOR4060
197T Malaysia4039
198A synonymous (GCc) KO_Seoul1870_2009_12_18_TmX
198V Malaysia5283, Malaysia9117
198G (GgA) BeijingXuanwu1945 (86T, 178M), Tomsk07 (131P, 225G)
. . . . WSN33,
. . . . H3N8 eqHeilongjiang10_2008, H6N1, H7N7 ext
199N (aAT) GuangdongSWL28, Milan80, Milan83, Iceland176,
. . . . S9, S7, M7, Sask, H5 (aCT),
. . . . H1N1 (1943, 46, 51) (aCT)
199D synonymous (GAc) swine Illinois, H5, H9N2
200A synonymous (GCc) swOR4060, S5
200T (aCA) FL31, RomaniaTimis2018, Australia (6), Asia (15), 
. . . . MilanUSHR1, Bilthoven4360901004,
. . . . ShizuokaC247_2009_11_08, H5, KO_Seoul1785_2009_11_TmX,
. . . . NepalNP09A294,
. . . . KuwaitN12991_2009_08_24,
. . . . tkDeutsche, swDeutsche,
. . . . H9N2
200S (tCA) NY1999_2010_01_18, NY0461, NY6945, NY5276,
. . . . NC57, SC46, WiscD0780, WiscS1338,  NJ11, DC_INS31,
. . . . China,
. . . . cheetahCA30954
. . . . H11 Avian tCt ext, tCc ext including dkViet2009
201H (cAT) Wisc1140, Darwin2140,
. . . . H3N8 (cAa, cga), H7N7 (cta, ctg)
202A (GcT) MXinDRE797 2010 TmX (280A, syn321L, 324I), IA14, KY25,
. . . . HK34360, Guangdong2282 (131P, 230I, 244I, 275A),
. . . . LiaoningShuncheng1145, LiaoningShuncheng1148 (131P, 230I, 244I, 275A),
. . . . Bilthoven4310901550 (89G), Bilthoven4360903104 (89G),
. . . . H9N2 (AcA, AcG)
202V synonymous (GTa) JiangsuXiaguan1411
202V synonymous (GTc) YAMAGATA778, YAMAGATA803, swIllinois,
. . . . H1N1 (1943, 46, 51)
204V synonymous (GTa) PA31, SHIZUOKA1573, 1918, S7
204V synonymous (GTa) TexasJMS367_2009_11_12, PA31,
. . . . AfghanN10767_2009_09, AfghanN10974_2009_09,
. . . . KuwaitN13111_2009_09_23,
. . . . Shizuoka1573, Niedersachsen34, RheinlandPfalz86,
. . . . 1918, S9, S7, M7, Sask,
. . . . H9N2 Israel 2009, H9N2 Iran 2008
205G synonymous (GGa) Texas76C2, Wisc (4),
. . . . AfghanN09836_2009_08, TurkeyTR19_2009 (233H)
. . . . Slovenia5662, Slovenia5711,
. . . . Iceland162M (225G), Iceland162Siat3 (225G),
. . . . tkDeutsche, swDeutsche,
. . . . S5, H3N8 (tCa), H9N2 (GCa), H6N1 (GGa), H7N7 (GGa)
205E (GaG) BadenWurttemberg8_2010, ShizuokaC247_2009_11_08
. . . . Alabama03_2010_03_01 mix,
. . . . H11 (Gat), H7N7 (Gaa), H7N7 dkVictoria1976 (GaG)
205W (tGG) Brno216_2009
206A CatS1161
206T (ACA) Extensive
206T (ACt) Georgia670_2010 (Europe)
207S synonymous (TCg) California01_2010
208K (AaA) US, UK, Canada, HK, MX, Italy (2), Australia (12), Asia (5),
. . . . BahrainN11890_2009_10, BahrainN11892_2009_10, Dakar 2010 (3)
. . . . Cyprus5870_2010 (214R, 225E, 324I),
. . . . swOR4060
208S Australia43, Australia45, H6N1
208G (gGA) NY6292, HubeiWuchang1407,
. . . . Avian H4N6, H9N2 (gaA)
208T Norway3440
208R synonymous (AGg) TexasJMS385_2009
209Y synonymous (TAt) ShanxiWanbolin337
209D NorthDakota15
210S synonymous (AGt) Bogota0466N, Malaysia9131, H9N2 (Aat)
210G (gGC) Bilthoven4360903119 (225E)
210N Texas76C2, H1N1 (1943, 46, 51)
211K (AAa) synonymous MXinDRE50617 (225G), Niedersachsen330
211R swOR4060_2009_12_31, 1918, H1N1 (1943, 46, 51)
212R swOR4060_2009_12_31, 1918, H1N1 (1943, 46, 51)
212E Vlad01 (225G), Argentina8574_41, IN21, HI30, Malaysia4039,
. . . . Latvia122498 (225G), Iwate1093
212N ME15
212T Anadyr177_F (225G), CA07X179, CA07X181
212K synonymous (AAa) NY1999_2010_01_18, NY0461, TexasJMS404_2009,
. . . . AfghanN11216_2009_10_16
213L TX15, Iowa04_2010, H5
213F synonymous (TTt) NY3230_2010_01_25 (100N, 159K), StPete99 (225E),
. . . . Sachsen156, IsraelMF4683, Georgia4805 (35I), Georgia670_2010 (165R)
214K synonymous (AAa) CalifVRDL81 (100N, 135I), San DiegoINS101_2009, NM13,
. . . . Iran20001, Iraq2587, CatS1937, ENG620,
. . . . China22811, GuangdongFutian1480,
. . . . NagasakiHA1015_2010_02_01 (135E, 377K),
. . . . NagasakiHA1017_2010_02_08 (135E, 377K, syn496A, 550K),
. . . . S5, H9N2
214E Kurgan01, Moldova (3), swOR4060_2009_12_31
214N ENG92960012, SHIZUOKA1514, Hessen48
214Q Wisc0936 (237L)
214R (AgG) Cyprus5870_2010 (208K, 225E, 324I)
215P synonymous (CCa) NY2372_2010_01_20 (233H), San DiegoINS101_2009,
. . . . Kuwait (4), SC33, Eng616, BZ_Bahia15525_42M_f (RRT),
. . . . NepalNP09A284, Thai0440, GuangdongyunchengSWL51,
. . . . swHK_2299_2009_10_22, swHK_NS1583_2009_10_22
215P synonymous (CCt) NY_WC37RG, MO02, Eng256, Lisboa171 (324I, 373H)
216E synonymous (GAg) BadenWurttemberg490_xL, Hamburg14_xL,
. . . . Thuringen189_xL, Thuringen227_xL, Bilthoven4360903109, 
. . . . Moldova (4), Belarus, Bosnia (3, 225G),
. . . . Bulgaria1369 (99T), Ostrava221_2010,
. . . . Iraq2587, Indiana,
. . . . tn, H9N2 (GTg)
218A synonymous (GCg) Belarus, GhanaN12987_2009_10,
. . . . H9N2 (GGg), H6N1
218A synonymous (GCt) Nebraska02_2010, Iraq2587,
. . . . WSN33
218E Texas77 (159S, syn173G, 275A, 377K, 454I)
218S (tCA) Georgia07_2010 mix
218T (aCA) Hiroshima201 (225G), KuwaitN12991_2009_08_24
. . . . BelgiumG4751_2009 mix, Latvia237_2010 mix (377K)
218V (GTa) GuangdongyunchengSWL51, Malaysia (2 mix wt)
218V (GTc) swIll02930, 2931, 2932, 2937 (2009-12-29, 30)
219I synonymous (ATt) Calif_SDINS35, CalifVRDL84 (35I), NY6939 (35I),
. . . . Ancona451_f, Lyon2490, Poitiers3691 (35I), Valladolid35 (35I),
. . . . RheinlandPfalz81, Berlin210, BadenWurttemberg511,
. . . . Saarland21 (35I), Luxembourg184_2010 (35I), Luxembourg251_2010 (35I),
. . . . Dakar 2010 (4, 35I), Cameroon463 (35I),
. . . . H5 (Act), H6N1 (gct, gat)
219T (AcA) Wisc0134 (225E), Ontario315107 (225E), RomaISS223,
. . . . Korea3623_2009_11_09 (131P, 226R, 280A), swOR4060_2009_12_31
220R synonymous (AGg) Mexico476, MexCtCIA4, Malaysia9451, H6N1
222R (AgA) ThaiTHB0405, ThaiTHB0408
223V synonymous (GTa) Utah59, ThaiTHB0390
. . . . H1N1 (1943, 1946, 1951), H6N1 mallSweden30/2005
223M CA33
224K SC18_VxX, Melbourne1_1946
224M NY5186
225D synonymous (GAc) HubeiWuchang1418,
. . . . swHK_NS1809_2009_12_03, swHK_NS1810_2009_12_03
225N BZ_SP53838, Ukraine mix wt, Victoria2125, Malaysia8860
. . . . Neimenggu-Hangjinhouqi51, EgyptN14648_2009_11,
. . . . IrelandM79555, IrelandM79556,
. . . . BadenWurttemberg502, et al
225E Extensive on multiple backgrounds, incl Kuwait, Ghana and Egypt.
. . . . Denmark1341 (158E, 264V), Cyprus5870_2010 (208K, 214R, 324I),
. . . . LaReunion3479, Morocco1088H (300S)
225G LvivN6_VxX with syn413K, UkDnip273 (GgT mix wt),
. . . . YaroslavlIIV196_2009_12_04_f  (89G & 4 silent H5N1 changes),
. . . . TurkeyTR20 (324I), Thessaloniki791_2010 mix (186P, syn233Y, 324I, 377K),
. . . . Latvia121488_2009 (377K), Georgia4484_2009 (158E, 377K),
. . . . Iceland162M, Iceland162Siat3, Denmark1900,
. . . . China mix,
. . . . NY7216 (148F),
. . . . H1N1 (1943, 46, 51), H9N2, H6N1
225G (Gga) RomaISS1897 & 1941, EgyptVacsera138,
. . . . EgyptN14644_2009_11_01, ex225E all with 300S, H6N1
225E+226R Russia (3), GermanyBY74, swMX4
226R synonymous (CAg) Alabama08, Texas45033567, Texas45131305,
. . . . S7, M7, S5, tn
226R Alabama01_2010, Trabzon01 (Turkey), GermanyMVHGW4_2009_12,
. . . . Korea3623_2009_11_09 (131P, 280A), China,
. . . . catItaly304678_2_2009_12_17_f, et al
227E synonymous (GAg) Wisc (10), Texas45130742,
. . . . Paris2573, Paris2590,
. . . . Avian H2 (Ggg)
227A swOR4060_2009_12_31, tkDeutsche, swDeutsche,
. . . . NJ11_1976_X53A, 1918,
. . . . H1N1 (1943, 46, 51)
227V (GtA) RomaISS50
227G (GgA) Utah20_VxX mix, Avian H2
228G synonymous (GGa) Arizona06, Lisboa108 (225E, syn346G),
. . . . Valladolid35 (35I),
. . . . GhanaFS1982 (syn139C, 206T, 261K, 296H, syn346G, 377K),
. . . . GhanaFS2206 (syn139C, 206T, 261K, 296H, syn346G),
. . . . ShanxiPingding351
. . . . S9, S7, M7, S5
. . . . H5N1
229R synonymous (AGg) swMX04 (225G, 226R), SichuanDongqu1818,
. . . . H6N1
230I (ATc) Sask, S9, S7, H6N1 (4), H7N7
230I (ATa) Wisc0337_2009_12_15 (275A, 377K),
. . . . H1N1 (1943, 46, 51),
. . . . H5N1 Gharbiyah 80% CFR, H3N8
230I (ATt) Guangdong2282 (131P, 202A, 244I, 275A),
. . . . LiaoningShuncheng1148 (131P, 202A, 244I, 275A),
. . . . H5N1, H6N1, H7N7, H9N2
230V (gTG) TexasJMS369_2009
231N synonymous (AAt) NY3230_2010_01_25 (100N, 159K), CalifVRDL36 mix (273K),
. . . . Lisboa104
231D Ankara05, OSAKA2143, GuangxiQinnan1187,
. . . . H9N2 2008, H6N1
231K Wisc0853, Wisc1915, Wisc2337
232Y synonymous (TAc) NY7216 (148F, 225G), TexasJMS386_2009,
. . . . Florida30, PuertoRico51,
. . . . S9, S7, M7, Sask,
. . . . H9N2, H5, H6N1
233Y synonymous (TAt) AthensINS85,
. . . . Thessaloniki788_2010 (194I, 324I, 377K),
. . . . Thessaloniki791_2010 mix (186P, 225G, 324I, 377K),
. . . . Hiroshima645,
. . . . H9N2 2008, H6N1
233H (cAC) NC Duke TmX cluster (5, mix, 225G, 225N), NY2372_2010_01_20,
. . . . AZ17 & Australia6, TurkeyTR19_2009 (syn205G),
. . . . swHK_189_2010_01_07
235A CatNS7632, CalifVRDL55
235I Wisc2489
236L synonymous (CTg) Wisc0099, H9N2 (gTg)
236V Eng93120020, ENG645, H9N2, H6N1
237I Delaware02_2010, Cal_SDINS69, England (2), Russia (4), Asia (4)
237L Wisc0936 (214Q), 1918, H1N1 (1943, 46, 51),
. . . . tn, H5, H9N2, H6N1
237V synonymous (GTg) Pennsylvania31, KuwaitN13111_2009_09_23,
. . . . AfghanN10767_2009_09, AfghanN10974_2009_09,
. . . . H9N2 (TTg), M7 (CTg)
238D Kaliningrad01 (225E+226R), tn
238K (aAG) Wisc2485 (225E), DjiboutiN13142_2009_12_08, Spain (3),
. . . . OrenburgIIV13_2010_03_02_xL_f (225G), China,
. . . . swOR4060,
. . . . Iowa_1943, H5, H9N2 2008, H6N1
238E synonymous (GAa) Extensive Wisc2424, EgyptN14648_2009_11,
. . . . Latvia122498, ThaiTHA0364, ShanxiChengqu547,
. . . . Cyprus5800_2010,
. . . . SC01_2010, MN01_2010,
. . . . H9N2 (aAa), H6N1 (aAa)
239P synonymous (CCt) ENG621, NY6939, swOR4060_2009_12_31
239P synonymous (CCa) Ancona508PG, Russia180, Australia60,
. . . . MS09, NV20, ME01_2010, tn,
. . . . H9N2, H6N1
240G synonymous (GGg) DC_INS24, H9N2, H6N1 (GGg), S9, S7, M7, Sask
240G synonymous (GGc) Wisc0636, H9N2 (GGc)
240E (GaA) Brandenburg34
241D synonymous (GAt) CatS1943, Colombia4117, swIll (3), S7, M7, tn, H5
241G NH17, ENG93040048
241E China22811, H9N2 (CAa, CAg), H6N1 (GAa, GAg)
242K synonymous (AAg) swOR4060_2009_12_31
244I ThaiCU_H9, Shiga1, Guangdong2282 (131P, 202A, 230I, 275A),
. . . . LiaoningShuncheng1148 (131P, 202A, 230I, 275A),
. . . . Ancona02, Stockholm29,
. . . . Alabama03_2010,
. . . . H1N1 (1946, 51), S9, S7, M7, Sask
244T synonymous (ACt) CatS1935, CatS2120
245F synonymous (TTt) Aswan2288 (189T, 377K)
246E synonymous (GAg) NorthCarolina56 (100N, syn137A, 377K),
. . . . S7, M7, 1918, tn, H5
246G (GgA) Iceland163_2009 mix (159D)

The truth is in the sequences.

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

Zoonotic H9N2 Avian Influenza Further Destabilises H1N1 Pandemic Genetics

Is the H1N1 Pandemic Influenza Reservoir Stable?

If you enjoy counting, even measuring by observation, please continue reading.

But you must realize that the iota, the jot and even the title, will be considered of value in this forthcoming exercise. Some in the science community appear to find the process of discovery by observation just too tedious.  If you are of that mindset, please direct your attention to any of the many “Science for Hire” venues where illogical, but comforting, summations are drawn from cleverly manipulated data streams.  Science sells today. But we sometimes speculate that science is becoming just another sell-out, an industry pursuing profit over knowledge?

On the other hand, if careful examination, even hard work, is part of your daily lab book, you'll find evidence in this discussion to introspect.

Leading public health officials continue even today to indicate that the pandemic virus is unchanged.  Keep that statement in mind as you read this analysis of heavy change activity in the pandemic reservoir, watching closely for the recent branching into genetic areas matching H9N2.

Also keep in mind that even single changes have demonstrated substantial importance.

Ongoing worldwide studies duplicated by independent, geographically dispersed laboratories, including the labs of those noted public health officials, indicate that a single polymorphism may produce a significant outcome within a Pandemic Influenza reservoir. Numerous accounts of important revisions are on record across a vast geography. The HA gene segment provides suitable examples for this discussion. 225G has produced a Vaccine Escape event in LvivN6, an elevated Case Fatality Rate and a substantial number of severe outcomes. Individual changes from 157 to 159 have also demonstrated “low reactor” status and registered as Vaccine Escape events.  When 230I entered the H5N1 Gharbiyah cluster in Egypt, the resultant Case Fatality Rate became 80% for that strain, a substantial increase from the accepted H5N1 CFR.

Three separate single genetic changes are well characterised in leading to various forms of Anti-Viral resistance. TamiFlu Resistance (TmX) has now dispersed widely in a pattern following the rapid spread of resistance in seasonal influenza via the same Single Nucleotide Polymorphism coding for 275Y on the Neuraminidase. Emergent and attractant H1N1 strains (Triple Reassortments again) co-circulating alongside the pandemic reservoir also carry 275Y. H5N1 inclusions increase in the pandemic reservoir with a continuous flow. The PB2 627K is confirmed as leading to increased replication speed in humans and has recently been documented in a second pandemic sequence. As we have maintained from the beginning of this pandemic, TamiFlu Resistance and 627K are foregone conclusions according to our calculations.

Our team noted an increase in Avian inclusions and recently predicted HA 230I for ΣPF11. The polymorphism was documented last week in Wisconsin (US) on a background that does not deter transmission. The geographic area has a notable increase in cross-linked activity. The individual sample, A/Wisconsin/629-D00337,  is primed for spread with 2 additional HA markers, 275A (TX, NM, CA and Sweden) and 377K (aggressively emerging). The NA carries 220K, a marker found on one cross-linked sequence from the Ukraine and across a wide US geographic pattern from December 2009 to the most recent 2010 sequences (North Carolina, New Hampshire, Wisconsin and Nebraska). The H6N1 Avian reservoir conserves 220K on the NA of 6 samples. We consider the Wisconsin0337 sample to be an excellent candidate as a universal donor of sorts due to limited polymorphisms, FlightPath intersecting location and the fact that each revision is currently an emergent change. 

A second variant of 230I has been recorded from southern China with A/Guangdong/2282.  Though the underlying 230I nucleotide coding and the overall background is different from the Wisconsin0337 sequence, Guangdong2282 remarkably carries the extremely rare 275A, a permutation found in less than ten samples within this pandemic reservoir.  Guangdong2282 displays a highly polymorphic HA with 131P, 202A, 230I, 244I and 275A.  All but 131P are rare. 202A is only found on one other human pandemic sequence, a 2010 TamiFlu Resistant case from Mexico.  Two of the four NA changes match 1918 (53I, syn315G) with potential H5N1 involvement on one other.  Convergence of numerous rare polymorphisms, including potential acquisitions from H5N1, H6N1, H9N2 and 1918, informs us that the viral reservoir is amply supplied for variation and is adamant about exercising fresh patterns.

H9N2, a "bird flu" serotype, has been recently evaluated for human pandemic potential.  By all appearances, the present H9N2 reservoir is not becoming a pandemic virus, but is very much influencing the genetic acquisition cycle of the currently circulating PF11 pandemic virus (pH1N1).  Which is worse, another species-jumping serotype entering the fray or a combinational virus with genetics from multiple pandemic potential reservoirs appending onto the current partially-adapted virus?  In either case, the Hydra Effect appears to be operating in full force.

Given this information, obvious questions begin to form. If one genetic change may potentiate variant clinical outcomes, drug resistance or Vaccine Escape, what is the potential for multiple changes producing a variant outcome? And if a single genetic change and/or multiple changes are capable of producing large changes in behaviour, should we, in turn, have a very high and accurate level of surveillance on this reservoir? And what should we do with that important information? Should our public health officials speak from a platform of candor and accuracy when carrying out the responsibilities of their trusted positions?

Let’s investigate now if the viral reservoir is, in fact, unchanged?

Approximately 86% of the Hemagglutinin positions between 186 and 244, including antigenic areas of the RBD, are on record as polymorphic. Only 8 positions in that range are stable.  Many positions rate multiple changes. The list presented today is certainly not comprehensive. For the sake of brevity, only one section is discussed from one gene segment (HA) covering just 59 amino acid positions. The extensive variation in that short range is documented in the trailing data. Tracking these revisions against various baselines has informed our studies over the past year.

The positional summary may perhaps be instructive for those who hold the belief that the pandemic reservoir is stable. This report may provide reversing guidance for those who make public statements to the effect that pandemic H1N1 is not changing. Although their multiple motivations to transmit these types of false “Feel Good” statements are somewhat discernable, the citizen requires the full story, the truth, to make informed decisions.

Those making these statements do, in fact, understand Primary Logic and Basic Science; they do know that for a vaccine to be considered widely useful, the viral reservoir must be cooperative and unchanging. They also know that this reservoir is vastly changed.  However, their jobs depend on providing a social message with a stated solution. Knowing that the vaccine is not useful against this present changed virus, they must by now realise that they have lost their stated solution.  The traditional public health strategy in these solution-less situations is obfuscation.  Re-education on basic fact, re-definition of truth, has now become the chief tenet, their tool of choice, to bridge that failure to solve. 

Science solves . . . crafting a clever press release is not an act of science.

The official repetition of the “All Clear” social messaging campaign cannot reverse the weight of the actual data. The presently circulating virus is hereby documented in this report as changed and changing. No amount of repetition invoking the “unchanged” myth, that mystical “Feel Good” chant, can conjure an environment that miraculously creates a stable viral reservoir or that alters the ongoing genetic acquisition cycle.

However, that ongoing strategy of repetition is apparently very effective in managing the perception and manipulating the belief of the unsuspecting public.  Sleight of hand is always discovered on careful observation . . . but will this reliance on myth be discovered soon enough?

Observe.

The viral reservoir backing this present H1N1 pandemic is far from stable and is actively acquiring new genetics. Current data does not indicate an immediate direction toward stability.

As is the nature with an IDRREAV, the positions reported here will not necessarily be the most important amino acid positions in the future. The reservoir will evade immunity and escape vaccine by heavily self-revising in the near future at key locations between 131 and 182 (emphasis at 155 to 177). Variation will occur with lower penetration at the head of the HA and from 272 downstream approximately 55 positions. Potential is very high that 22I will achieve density in one or more sub-clades. Expect 100N to spread and penetrate initially on sub-clades without the 22I appearances. South American polymorphisms from their fatal mid-pandemic strains of 2009 will recycle into the United States and other Northern Hemisphere nations with substantial thrust in the coming 90 days. Acceleration of the Avian based cross-linking will continue in the Western world.

Bear in mind also that a solid portion of the changes documented in this current list will become fixed even as additional donations are accumulated. The zoonotic movement from birds into human PF11 sequences is earnestly progressing in the most recent 45 days of available data. Several polymorphisms, HA and NA, from the recent 2010 Georgia hospitalization resurgence may have originated in Avian Influenza samples.

Expect continued acquisition from Avian H5N1, H6N1 and H1N1, and also watch the acceleration from one particularly new Avian donor serotype. H9N2 demonstrated a human jump in late 2008 and has very recently become fully engaged in ΣPF11 genetics with a well-defined etching on the newest cross-linked sequences. The reservoir flux will also be influenced by Swine H1N2 and H1N1 (emphasis on 3 certain emergent strains).

Is the Pandemic Influenza Reservoir Stable?

You decide . . .

186S synonymous (TCc) Russia61, BZSP53823_2009_08_01_f,
. . . . BadenWurttemberg8_2010, TexasJMS387_2009_12_08,
. . . . KO_Daegu1873_2009_12_16_TmX,
. . . . H9N2 (cCc, cac)
186P (cCT) CalifVRDL7, UkraineChernihiv857, Ankara17
186F (TtT) Ankara26
187T synonymous (ACc) Berlin164, S5, 1918, H9N2
187A (gCT) TexasJMS405_2009, TexasJMS406_2009,
. . . . H5 (gaT)
188T (AcT) swThaiCURA75_2010_01,
. . . . H6N1 dkHK202_1977, dkKOS17_2003,
. . . . H7N7 extensive including human fatality
188S synonymous (AGc) NY6943_xL
188N SC16, SC31, NY3502, ME15, CatS1187, Milan433, Kaifu4142,
. . . . Japan, Bilthoven4360903023,
. . . . swHK_NS1809_2009_12_03 (189T), swHK_NS1810_2009_12_03
. . . . S5, H5
188I Growing in US on cross-linked background (4), BZSP53823 (186S),
. . . . H1N1 (1943, 46, 51)
189V Sydney2503, Texas46172731,
. . . . Sask, H6N1 mallMaryland887_2002
189S Wisc1434
189T Extensive in US incl NY7020 (77N), on cross-linkage (4) incl NY6943_xL,
. . . . Ontario328474
. . . . swHK_NS1809_2009_12_03 (188N)
. . . . H5N1 2009, H6N1, H9N2 2008
189A synonymous (GCc), Georgia01_2010, Georgia 2010 (+5), swOR4060
190D synonymous (GAt) Nebraska02_2010, Milan326, UkraineZakarpatska830,
. . . . AfghanN09833_2009_08
. . . . 1918, H1N1 (1943, 51)
190Y SwedenMalmoe1_2010_01_01, H6N1 (tTG)
191R Chengdu18 (131P), GuangdongSWL28
192H GuangdongSWL28
192Q synonymous (CAg) RomaISS50, Nebraska01_2010, H1N1 (1943, 46)
193S synonymous (AGc) SC18, US 2010 (4), Milan294, Japan,
. . . . AfghanN10765_2009_09
. . . . H3N8 AGc aplatBelgium12827_2007,
. . . . H6N1 AGc chkTaiwan0706_2003,
. . . . H9N2 Aac dkViet2009,
. . . . H11Nx Aac dkViet2009
193G (gGT) AR08, Cal_SDINS04
. . . . H5N1 (gGg), H3N8 (gaT, gac, gaa), H11 (gac, gat)
193N (AaT) Washington72, H3N8, H6N1, H9N2, H11
193R (cGT) catItaly304678_1_2009_12_17_f, Origin Unknown
194I NC38E3, VA27, SC18, Bangladesh3009, StPete59, StPete99
194L synonymous (CTa) Japan4081, tn
. . . . H9N2 2008 (tTa), H6N1 chkTaiwan1205_2001 (CTa)
194L synonymous (CTt) TexasJMS385_2009, EgyptN11640_2009_10
. . . . H9N2 dkVietnamOIE2327_2009
196Q synonymous (CAa) Wisc (3), Moldova (3), Malaysia (2), Milan326,
. . . . Pavia (6), Ankara18, NordrheinWestfalen106, swOR4060
197T Malaysia4039
198A synonymous (GCc) KO_Seoul1870_2009_12_18_TmX
198V Malaysia5283, Malaysia9117
199N GuangdongSWL28, Milan80, Milan83, S9, S7, M7, Sask, H5 (aCT),
. . . . H1N1 (1943, 46, 51) (aCT)
199D synonymous (GAc) swine Illinois, H5, H9N2
200A synonymous (GCc) swOR4060, S5
200T (aCA) FL31, RomaniaTimis2018, Australia (6), Asia (13), 
. . . . MilanUSHR1, Bilthoven4360901004,
. . . . ShizuokaC247_2009_11_08, H5, KO_Seoul1785_2009_11_TmX,
. . . . KuwaitN12991_2009_08_24
. . . . tkDeutsche, swDeutsche,
. . . . H9N2
200S (tCA) NY1999_2010_01_18, NY0461, NY6945, NY5276,
. . . . NC57, SC46, WiscD0780, WiscS1338,  NJ11, DC_INS31,
. . . . cheetahCA30954
. . . . H11 Avian tCt ext, tCc ext including dkViet2009
201H (cAT) Wisc1140, Darwin2140,
. . . . H3N8 (cAa, cga), H7N7 (cta, ctg)
202A (GcT) MXinDRE797 2010 TmX (280A, syn321L, 324I), IA14, KY25,
. . . . HK34360, Guangdong2282 (230I, 275A),
. . . . Bilthoven4310901550 (89G), Bilthoven4360903104 (89G),
. . . . H9N2 (AcA, AcG)
202V synonymous (GTc) YAMAGATA778, YAMAGATA803, swIllinois,
. . . . H1N1 (1943, 46, 51)
204V synonymous (GTa) PA31, SHIZUOKA1573, 1918, S7
204V synonymous (GTa) TexasJMS367_2009_11_12, PA31,
. . . . AfghanN10767_2009_09, AfghanN10974_2009_09,
. . . . KuwaitN13111_2009_09_23,
. . . . Shizuoka1573, Niedersachsen34, RheinlandPfalz86,
. . . . 1918, S9, S7, M7, Sask,
. . . . H9N2 Israel 2009, H9N2 Iran 2008
205E (GaG) BadenWurttemberg8_2010, ShizuokaC247_2009_11_08
. . . . Alabama03_2010_03_01 mix,
. . . . H11 (Gat), H7N7 (Gaa), H7N7 dkVictoria1976 (GaG)
205G synonymous (GGa) Texas76C2, AfghanN09836_2009_08, Wisc (4),
. . . . tkDeutsche, swDeutsche,
. . . . S5, H3N8 (tCa), H9N2 (GCa), H6N1 (GGa), H7N7 (GGa)
206A CatS1161
206T Extensive
207S synonymous (TCg) California01_2010
208K US, UK, Canada, HK, MX, Italy (2), Australia (12), Asia (3),
. . . . BahrainN11890_2009_10, BahrainN11892_2009_10,
. . . . swOR4060
208S Australia43, Australia45, H6N1
208G NY6292
208T Norway3440
208R synonymous (AGg) TexasJMS385_2009
209D NorthDakota15
210G (gGC) Bilthoven4360903119 (225E)
210S synonymous (AGt) Bogota0466N, Malaysia9131, H9N2 (Aat)
210N Texas76C2, H1N1 (1943, 46, 51)
211K synonymous MXinDRE50617 (225G)
211R swOR4060_2009_12_31, 1918, H1N1 (1943, 46, 51)
212R swOR4060_2009_12_31, 1918, H1N1 (1943, 46, 51)
212E Vlad01 (225G), Argentina8574_41, IN21, HI30, Malaysia4039
212N ME15
212T Anadyr177_F (225G), CA07X179, CA07X181
212K synonymous (AAa) NY1999_2010_01_18, NY0461, TexasJMS404_2009,
. . . . AfghanN11216_2009_10_16
213L TX15, Iowa04_2010, H5
213F synonymous (TTt) NY3230_2010_01_25 (100N, 159K), StPete99 (225E),
. . . . Sachsen156
214E Kurgan01, Moldova (3), swOR4060_2009_12_31
214N ENG92960012, SHIZUOKA1514, Hessen48
214Q Wisc0936 (237L)
214K synonymous (AAa) CalifVRDL81 (100N, 135I), San DiegoINS101_2009, NM13,
. . . . CatS1937, ENG620, China22811, S5,
. . . . H9N2
215P synonymous (CCa) NY2372_2010_01_20 (233H), San DiegoINS101_2009,
. . . . SC33, Eng616, GuangdongyunchengSWL51, BZ_Bahia15525_42M_f (RRT),
. . . . Kuwait (4), swHK_2299_2009_10_22, swHK_NS1583_2009_10_22
215P synonymous (CCt) NY_WC37RG, MO02, Eng256
216E synonymous (GAg) BadenWurttemberg490_xL, Hamburg14_xL,
. . . . Thuringen189_xL, Thuringen227_xL, Bilthoven4360903109, 
. . . . Moldova (4), Belarus, Bosnia (3, 225G), Indiana,
. . . . tn, H9N2 (GTg)
218A synonymous (GCg) Belarus, GhanaN12987_2009_10, H9N2 (GGg), H6N1
218A synonymous (GCt) Nebraska02_2010
218E Texas77 (159S, syn173G, 275A, 377K, 454I)
218S (tCA) Georgia07_2010 mix
218T Hiroshima201 (225G), KuwaitN12991_2009_08_24
218V (GTa) GuangdongyunchengSWL51, Malaysia (2 mix wt)
218V (GTc) swIll02930, 2931, 2932, 2937 (2009-12-29, 30)
219I synonymous (ATt) Calif_SDINS35, CalifVRDL84 (35I), NY6939 (35I),
. . . . Ancona451_f, Lyon2490,
. . . . RheinlandPfalz81, Berlin210, BadenWurttemberg511,
. . . . H5 (Act), H6N1 (gct, gat)
219T (AcA) Wisc0134 (225E), Ontario315107 (225E), RomaISS223,
. . . . Korea3623_2009_11_09 (131P, 226R, 280A), swOR4060_2009_12_31
220R synonymous (AGg) Mexico476, Malaysia9451, H6N1
223V synonymous (GTa) Utah59, H1N1 (1943, 46, 51),
. . . . H6N1 mallSweden30_2005
223M CA33
224K SC18_VxX, Melbourne1_1946
224M NY5186
225D synonymous (GAc) swHK_NS1809_2009_12_03, swHK_NS1810_2009_12_03
225N BZ_SP53838, Ukraine mix wt, Victoria2125, Malaysia8860
. . . . EgyptN14648_2009_11, et al
225E Extensive on multiple backgrounds, incl Kuwait, Ghana and Egypt
225G LvivN6_VxX with syn413K, UkDnip273 (GgT mix wt),
. . . . YaroslavlIIV196_2009_12_04_f  (89G & 4 silent H5N1 changes)
. . . . NY7216 (148F),
. . . . H1N1 (1943, 46, 51), H9N2, H6N1
225G (Gga) RomaISS1897 & 1941, EgyptVacsera138,
. . . . EgyptN14644_2009_11_01, ex225E all with 300S, H6N1
225E+226R Russia (3), GermanyBY74, swMX4
226R Alabama01_2010, Trabzon01 (Turkey), GermanyMVHGW4_2009_12,
. . . . Korea3623_2009_11_09 (131P, 280A), catItaly304678_2_2009_12_17_f, et al
227A swOR4060_2009_12_31, NJ11_1976_X53A, 1918,
. . . . H1N1 (1943, 46, 51)
227V RomaISS50
227G Utah20 with wt mix
229R synonymous (AGg) swMX04 (225G, 226R), H6N1
230I Wisc0337_2009_12_15 (275A), Guangdong2282 (131P, 202A, 275A),
. . . . H1N1 (1943, 46, 51), H5 Gharbiyah 80% CFR, H9N2, H6N1
230V (gTG) TexasJMS369_2009
231D Ankara05, OSAKA2143, H9N2 2008, H6N1
231N synonymous (AAt) NY3230_2010_01_25 (100N, 159K), CalifVRDL36
231K Wisc0853, Wisc1915, Wisc2337
232Y synonymous (TAc) NY7216 (148F, 225G), TexasJMS386_2009,
. . . . Florida30, PuertoRico51,
. . . . S9, S7, M7, Sask,
. . . . H9N2, H5, H6N1
233Y synonymous (TAt) AthensINS85, Hiroshima645, H9N2 2008, H6N1
233H (cAC) NC Duke TmX cluster (5, mix, 225G, 225N), NY2372_2010_01_20,
. . . . AZ17 & Australia6, swHK_189_2010_01_07
235A CatNS7632, CalifVRDL55
235I Wisc2489
236L synonymous (CTg) Wisc0099, H9N2 (gTg)
236V Eng93120020, ENG645, H9N2, H6N1
237I Delaware02_2010, Cal_SDINS69, England (2), Russia (4), Asia (2)
237L Wisc0936 (214Q), 1918, H1N1 (1943, 46, 51),
. . . . tn, H5, H9N2, H6N1
237V synonymous (GTg) Pennsylvania31, KuwaitN13111_2009_09_23,
. . . . AfghanN10767_2009_09, AfghanN10974_2009_09,
. . . . H9N2 (TTg), M7 (CTg)
238D Kaliningrad01 (225E+226R), tn
238K (aAG) Wisc2485 (225E), DjiboutiN13142_2009_12_08, Spain (2),
. . . . OrenburgIIV13_2010_03_02_xL_f (225G), China,
. . . . swOR4060,
. . . . Iowa_1943, H5, H9N2 2008, H6N1
238E synonymous (GAa) Extensive Wisc2424, EgyptN14648_2009_11,
. . . . SC01_2010, MN01_2010,
. . . . H9N2 (aAa), H6N1 (aAa)
239P synonymous (CCt) ENG621, NY6939, swOR4060_2009_12_31
239P synonymous (CCa) Ancona508PG, Russia180, Australia60, ME01_2010, tn,
. . . . H9N2, H6N1
240G synonymous (GGg) DC_INS24, H9N2, H6N1 (GGg), S9, S7, M7, Sask
240G synonymous (GGc) Wisc0636, H9N2 (GGc)
240E (GaA) Brandenburg34
241D synonymous (GAt) CatS1943, tn
241G NH17, ENG93040048
241E China22811, H9N2 (CAa, CAg), H6N1 (GAa, GAg)
242K synonymous (AAg) swOR4060_2009_12_31
244I ThaiCU_H9, Guangdong2282 (131P, 202A, 230I, 275A), Shiga1,
. . . . Ancona02, Stockholm29,
. . . . Alabama03_2010, H1N1 (1946, 51), S9, S7, M7, Sask
244T synonymous (ACt) CatS1935, CatS2120

The truth is in the sequences.

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