The UK HPA Weekly National Influenza Reports covering the emerging epidemic from the past two weeks (Week 51 and Week 52) provide insight into data scarcity surrounding anti-viral drug resistance.
Oseltamivir-resistance may be determined genetically from a Single Nucleotide Polymorphism (SNP) H275Y on the Neuraminidase. Clinical anti-viral resistance and / or ineffectiveness in Pandemic H1N1 Influenza continues to manifest much more widely than can be attributed to the genetic variance of NA 275Y. In the future, other factors may be identified as genetically leading to the clinical manifestations in cases that do not demonstrate H275Y, but for the moment, the measurement is at that single change.
The HPA Week 51 data reported 3 TmX cases from 402 tested (~0.75%).
The HPA Week 52 data reported 5 TmX cases from 336 tested (~1.49%).
As you can see, the percentage of resistant cases week over week increased by 99%. Unfortunately, data sparsity alongside the fact of taking percentages of percentages may not allow this figure to be fully reliable for decision-making.
On the other hand, in a crisis when faced with limited testing capacity and limited testing foundation, these are the types of acceleration / deceleration calculations that must be made. Data that is available is used. GeneWurx would like to see clinical meta-data paired with genetic sequences to assist in pinpointing various HA polymorphisms that may also be associated with drug resistance, such as those trailing HA aa500.
GeneWurx has prepared an Excel spreadsheet so that the public may track any ongoing official and / or unofficial data concerning Anti-Viral resistance patterns.
GeneWurx_UK_2010_2011_Severe_Wave_TmX_v0.xls
Bear in mind that a recent seasonal influenza rapidly progressed from Anti-Viral sensitivity to Anti-Viral resistance across the world in less than one full season when the percentage of strains demonstrating NA H275Y reached approximately 2%.
More than 100 drug-resistant human Pandemic H1N1 sequences are on file considering just North America and Asia. Washington01_2010_04_02_TmX from the United States registered with 33 polymorphisms across the HA and NA gene segments. In August 2010, GeneWurx evaluated 7 sequences from Japan with extensive HA diversity and H275Y TamiFlu Resistance.
With drug resistant, hypermorphic strains carrying shared HA polymorphisms now being documented across a wide geography, will the resistant 2% begin to spread in Winter 2010-2011?
Showing posts with label H275Y. Show all posts
Showing posts with label H275Y. Show all posts
2010-05-05
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.
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.
2010-03-31
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.
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.
2009-12-03
TamiFlu Resistant Sequence #14 from Spain in Late November Carries Cross Segment Pair of Markers from the Ukraine
HA and NA CatNS7362 is the most recent official entry into the TamiFlu Resistant list of 14 sequences. This Spanish sequence sampled 2009-11-26 from a male in Catalonia also becomes the first recorded TamiFlu Resistant strain to participate in the cross segment pairing of HA syn413K and NA syn407V.
The NA of CatNS7362 is novel at the nucleotide level with no peer within ΣPF11. The NA is an exact nucleotide match to A/Singapore/ON1156 (2009-07-14) and A/Catalonia/S1702 (2009-11-02) except for the SNP encoding the antiviral resistance. The 7 polymorphisms found on the HA and the NA of this sample indicate a similar hyper-morphic behaviour that we saw with the Italian TamiFlu Resistant sequence, Pavia21. Three of the polymorphisms are silent. Inclusions are noted that previously appear on other sequences from Spain, Swine H1N1, Swine H1N2, Avian H1N1, Human H5N1, Avian H5N1 and Avian H6N1.
NA Amino Acid Codings to 3 Rare Polymorphisms
encoded from T447C, ATt->ATc
Rare to ΣPF11 with 2 instances from Spain and 1 from Singapore.
CatS1687
CatS1702
SingOn1156
syn407V
encoded from T1221C, GTt->GTc
Rare to ΣPF11 with 37 instances, yet common to Spain with 15 and the Ukraine with 9.
Progenitors may include:
H5N1 Human
H5N1 Avian
On CatNS7362 TamiFlu Resistance is indicated in typical PF11 fashion via a Single Nucleotide Polymorphism coding for 275Y on the Neuraminidase. The sequence displays the following NA Quadruple Combination:
106I, 248D, 275Y, 286S
106I is implied for CatNS7362 based on previous patterns as that portion of the sequence is truncated.
The following permutations are now represented on the fourteen PF11 anti-viral resistant sequences:
106V, 248N, 275Y, 286S = WA28, WA29, TX47
106I, 248N, 275Y, 286S = Osaka180
106I, 248D, 275Y, 286S = HK2369, Yamaguchi22, Denmark528, Hunan SWL3, Singapore57, Tokushima2, Iwate3, Quebec147365, Pavia21, CatNS7362
Until the 2009-08-21 deposit of the two Washington sequences, all 275Y TamiFlu-Resistant specimens on PF11 backgrounds were paired with 106I. We continue to see only 3 of the 13 with 106V. The addition of CatNS7362 heavily leverages position 248 toward Aspartate (D) with 10 specimens versus 4 with Asparagine (N). No TamiFlu Resistant specimen on file displays 286G as yet.
HA Amino Acid Codings to 2 Novel and 2 Rare Polymorphisms
CatS1687 is the singular instance within ΣPF11.
Progenitors may include:
H1N1 Swine
H1N2 Swine
H6N1 Avian
235A
Novel to ΣPF11.
Progenitors may include:
H1N2 Swine
Swine/Minnesota/1713/2000
SW/MN/16356/2001
H6N1 Avian
Chukkar (first base SNP required)
397D
Novel to ΣPF11.
Progenitors may include:
H6N1 Avian
syn413K
encoded from A1281G, AAa->AAg
Rare to ΣPF11 with 74 instances, yet common to Spain (12), the Ukraine (4), Japan (28) and Norway (9).
Progenitors may include:
H1N1 Avian
red-winged tinamou/Argentina/MP1/2008
The NA of CatNS7362 is novel at the nucleotide level with no peer within ΣPF11. The NA is an exact nucleotide match to A/Singapore/ON1156 (2009-07-14) and A/Catalonia/S1702 (2009-11-02) except for the SNP encoding the antiviral resistance. The 7 polymorphisms found on the HA and the NA of this sample indicate a similar hyper-morphic behaviour that we saw with the Italian TamiFlu Resistant sequence, Pavia21. Three of the polymorphisms are silent. Inclusions are noted that previously appear on other sequences from Spain, Swine H1N1, Swine H1N2, Avian H1N1, Human H5N1, Avian H5N1 and Avian H6N1.
NA Amino Acid Codings to 3 Rare Polymorphisms
- syn149I
- 275Y
- syn407V
encoded from T447C, ATt->ATc
Rare to ΣPF11 with 2 instances from Spain and 1 from Singapore.
CatS1687
CatS1702
SingOn1156
syn407V
encoded from T1221C, GTt->GTc
Rare to ΣPF11 with 37 instances, yet common to Spain with 15 and the Ukraine with 9.
Progenitors may include:
H5N1 Human
H5N1 Avian
On CatNS7362 TamiFlu Resistance is indicated in typical PF11 fashion via a Single Nucleotide Polymorphism coding for 275Y on the Neuraminidase. The sequence displays the following NA Quadruple Combination:
106I, 248D, 275Y, 286S
106I is implied for CatNS7362 based on previous patterns as that portion of the sequence is truncated.
The following permutations are now represented on the fourteen PF11 anti-viral resistant sequences:
106V, 248N, 275Y, 286S = WA28, WA29, TX47
106I, 248N, 275Y, 286S = Osaka180
106I, 248D, 275Y, 286S = HK2369, Yamaguchi22, Denmark528, Hunan SWL3, Singapore57, Tokushima2, Iwate3, Quebec147365, Pavia21, CatNS7362
Until the 2009-08-21 deposit of the two Washington sequences, all 275Y TamiFlu-Resistant specimens on PF11 backgrounds were paired with 106I. We continue to see only 3 of the 13 with 106V. The addition of CatNS7362 heavily leverages position 248 toward Aspartate (D) with 10 specimens versus 4 with Asparagine (N). No TamiFlu Resistant specimen on file displays 286G as yet.
HA Amino Acid Codings to 2 Novel and 2 Rare Polymorphisms
- 165N
- 235A
- 397D
- syn413K
CatS1687 is the singular instance within ΣPF11.
Progenitors may include:
H1N1 Swine
H1N2 Swine
H6N1 Avian
235A
Novel to ΣPF11.
Progenitors may include:
H1N2 Swine
Swine/Minnesota/1713/2000
SW/MN/16356/2001
H6N1 Avian
Chukkar (first base SNP required)
397D
Novel to ΣPF11.
Progenitors may include:
H6N1 Avian
syn413K
encoded from A1281G, AAa->AAg
Rare to ΣPF11 with 74 instances, yet common to Spain (12), the Ukraine (4), Japan (28) and Norway (9).
Progenitors may include:
H1N1 Avian
red-winged tinamou/Argentina/MP1/2008
2009-11-27
France Follows Suit on Continent with 225G in Fatalities, Including a 225G Case with TamiFlu Resistance
France announces the presence of 225G associated with fatalities and indicates that one of the 225G strains is also TamiFlu Resistant.
Less than one week after the first official announcement from Norway, western Europe has a growing coverage of confirmed and probable 225G cases. As we mentioned on the 23rd of November, many countries will now open their databases concerning this RBD change. Those databases will confirm not that 225G is spreading, but that 225G was already widely dispersed and is spreading faster than we had previously been led to believe.
A glaring signal is apparent concerning the public's right to information that may protect their health. Release of important policy-making and family protection information has been blocked as the taxpayer-funded research centers and public health officials continue to withhold even the sparse data from the limited surveillance that has been conducted.
The leading world health agency reports a rise in TamiFlu Resistant sequences to 75 cases, geographically dispersed, while continuing to read the script of "spontaneous mutation, not transmitting" over the increasing set of clustered cases. All TamiFlu Resistant cases from PF11 have had the same Single Nucleotide Polymorphism coding for 275Y in the Neuraminidase and this French case is expected to follow suit. Not random and not spontaneous. We have tracked the details of the 13 available public anti-viral resistant sequences for variation.
225G is now being reported widely as countries increase transparency concerning the antigenic diversity and transmissibility of strains carrying this important Receptor Binding Domain change that has, on lab examination of the 1918 strains, conferred dual receptor specificity for tissue in the upper respiratory system and the deep lung tissue.
Countries with Probable * or Confirmed 225G
Several questions come to mind concerning the French report considering the paired cross-segment changes on the Norway3364 sample from September, HA syn413K and NA syn407V. At the instant that research centers are identifying cross-segment linkages, we are now presented with a second set of pairs crossing the same two segments, HA 225G and NA 275Y.
Are the French cases contemporary? What are the clinical details? Note also that France published one of the first 225E sequences with Paris2591 from a 23M on 2009-05-01.
225G and 225E strains are co-circulating around the world, in one French case with TamiFlu Resistance, killing hosts quickly by destroying the lungs. Of deepest interest is the exhibition of clear vaccine escape signals if the low reactor status update of one recent Ukraine 225G, LvivN6, is validated. Antigenic diversity, whether due to viral response to human immunity, anti-viral selection pressure or vaccine pressure, is a certainty.
ΣPF11 is now officially Hydra.
Less than one week after the first official announcement from Norway, western Europe has a growing coverage of confirmed and probable 225G cases. As we mentioned on the 23rd of November, many countries will now open their databases concerning this RBD change. Those databases will confirm not that 225G is spreading, but that 225G was already widely dispersed and is spreading faster than we had previously been led to believe.
A glaring signal is apparent concerning the public's right to information that may protect their health. Release of important policy-making and family protection information has been blocked as the taxpayer-funded research centers and public health officials continue to withhold even the sparse data from the limited surveillance that has been conducted.
The leading world health agency reports a rise in TamiFlu Resistant sequences to 75 cases, geographically dispersed, while continuing to read the script of "spontaneous mutation, not transmitting" over the increasing set of clustered cases. All TamiFlu Resistant cases from PF11 have had the same Single Nucleotide Polymorphism coding for 275Y in the Neuraminidase and this French case is expected to follow suit. Not random and not spontaneous. We have tracked the details of the 13 available public anti-viral resistant sequences for variation.
225G is now being reported widely as countries increase transparency concerning the antigenic diversity and transmissibility of strains carrying this important Receptor Binding Domain change that has, on lab examination of the 1918 strains, conferred dual receptor specificity for tissue in the upper respiratory system and the deep lung tissue.
Countries with Probable * or Confirmed 225G
- United States
- Brasil
- Spain
- Japan
- Hong Kong *
- China
- Mexico
- Russia
- Australia
- Saudi Arabia
- Ukraine
- France *
- Norway
- Sweden *
- Finland *
- Singapore (4 with 225X encoded from aNy nucleotide) *
Several questions come to mind concerning the French report considering the paired cross-segment changes on the Norway3364 sample from September, HA syn413K and NA syn407V. At the instant that research centers are identifying cross-segment linkages, we are now presented with a second set of pairs crossing the same two segments, HA 225G and NA 275Y.
Are the French cases contemporary? What are the clinical details? Note also that France published one of the first 225E sequences with Paris2591 from a 23M on 2009-05-01.
225G and 225E strains are co-circulating around the world, in one French case with TamiFlu Resistance, killing hosts quickly by destroying the lungs. Of deepest interest is the exhibition of clear vaccine escape signals if the low reactor status update of one recent Ukraine 225G, LvivN6, is validated. Antigenic diversity, whether due to viral response to human immunity, anti-viral selection pressure or vaccine pressure, is a certainty.
ΣPF11 is now officially Hydra.
2009-11-22
TamiFlu Resistance #13 from Italy: Novel with Swine Inclusion plus 4 Rare PF11 Amendments
The thirteenth TamiFlu Resistant specimen with a publicly available sequence, A/Pavia/21, was deposited Friday at GenBank with only Segment 6 (NA). The sample is contemporary and was taken 2009-11-16 on a nasal swab from a host with no gender or age identification in Pavia, a city of 71,000 in the Lombardy region of north central Italy. This Neuraminidase is remarkable due to the number and range of polymorphisms though the sequence is truncated 35 bases from the end.
The NA of Pavia21 is novel at the amino acid and the nucleotide level with no peer within ΣPF11, nor in the TamiFlu Resistant subset. The 5 polymorphisms on this sequence, if acquired via recombination, require a wide set of donors or more likely coincident recombination and adaptation events. Inclusions are noted that previously appear on Swine H1N1 (recent and 1931), Avian H1N1, Seasonal H1N1, Avian H5N1, Avian H6N1, Avian H10N1, Avian H11N1 and on very small and diverse sets of European PF11 sequences.
Three of the polymorphisms are silent. No combination of any 2 of the 5 signals seems to appear on documented public sequences. None of the signals other than 275Y appear on any previous PF11 TamiFlu-Resistant sequence.
NA Amino Acid Codings to 1 Novel Polymorphism and 4 Rare Signals
syn70S
encoded from C210T, AGc->AGt
A/Catalonia/NS675 (2009-06-08) is the singular ΣPF11 peer.
332K
Novel to ΣPF11.
Progenitors may include:
H5N1 Avian Asia 2005, 2006, 2007, 2008
H6N1 Avian Europe 2005
H1N1 Swine 1977, 2002
H1N1 Seasonal 2007 (230I)
NCsw36883 (212E)
HKswNS1659
Iowa human swine worker 2005 H1N1 (IA/CEID23/2005)
syn360G
encoded from G1080A, GGg->GGa
Rare to ΣPF11 with 4 French instances in early pandemic.
Paris2590
Paris2591 (HA:225E)
Paris2592
Paris2604
Progenitors may include:
H1N1 Human North America 2007, Middle East 2006, 2007
H1N1 Avian North America 2006, 2007, 2008
H1N1 Avian Asia 2006
H1N1 Swine North America 1931, 2003, 2004, 2005, 2006
H1N1 Swine US 1931
H1N1 Swine Asia 1993, 2001, Europe 2001
H5N1 Avian North America 2005
H6N1 Avian North America 2007, Asia 2006
H10N1 Avian North America 2007
H11N1 Avian North America 2002
syn398E
encoded from G1194A, GAg->GAa
Rare to ΣPF11 with 7 instances.
Italy160 (July from Veneto)
Spain with 5 sequences as recently as 2009-10-28
Canada (May)
Progenitors unknown; however, a 12 residue span in this area, including residue 398, revises for WSN33 and H5N1 Human.
On Pavia21 TamiFlu Resistance is indicated in typical PF11 fashion via a Single Nucleotide Polymorphism coding for 275Y on the Neuraminidase. The sequence displays the following NA Quadruple Combination:
106I, 248D, 275Y, 286S
The following permutations are now represented on the thirteen PF11 anti-viral resistant sequences:
106V, 248N, 275Y, 286S = WA28, WA29, TX47
106I, 248N, 275Y, 286S = Osaka180
106I, 248D, 275Y, 286S = HK2369, Yamaguchi22, Denmark528, Hunan SWL3, Singapore57, Tokushima2, Iwate3, Quebec147365, Pavia21
Until the 2009-08-21 deposit of the two Washington sequences, all 275Y TamiFlu-Resistant specimens on PF11 backgrounds were paired with 106I. We continue to see only 3 of the 13 with 106V. The addition of Pavia21 heavily leverages position 248 toward Aspartate (D) with 9 specimens versus 4 with Asparagine (N). No TamiFlu Resistant specimen on file displays 286G as yet.
Pavia21 is the most hypermorphic TamiFlu-Resistant PF11 strain seen since the oddities from the immuno-compromised patients in Washington. Four changes other than H275Y is unusual in a single sequence.
We are quite impressed with the Influenza reservoir's ability to recycle data between serotypes without reassortment. Unless this sample were exposed to low level radiation during incubation, a series of accumulative recombinations have occurred over a very short time period or a triple co-infection enlisted all variants to build Pavia21 within a single host using an adaptation event to smooth the topping.
The most probable explanation is an accumulation of recombinations across the hypermorphic Catalonia region then exporting data to Italy via wild birds with a single co-incident adaptation event within the eventual host. Additionally, our team would not be at all surprised to find 225E on the HA of this patient's virus if the data is eventually published.
At any measure, another new background is now carrying TamiFlu Resistance in a central flyway for Influenza's primary transportation vector, wild birds.
The NA of Pavia21 is novel at the amino acid and the nucleotide level with no peer within ΣPF11, nor in the TamiFlu Resistant subset. The 5 polymorphisms on this sequence, if acquired via recombination, require a wide set of donors or more likely coincident recombination and adaptation events. Inclusions are noted that previously appear on Swine H1N1 (recent and 1931), Avian H1N1, Seasonal H1N1, Avian H5N1, Avian H6N1, Avian H10N1, Avian H11N1 and on very small and diverse sets of European PF11 sequences.
Three of the polymorphisms are silent. No combination of any 2 of the 5 signals seems to appear on documented public sequences. None of the signals other than 275Y appear on any previous PF11 TamiFlu-Resistant sequence.
NA Amino Acid Codings to 1 Novel Polymorphism and 4 Rare Signals
- syn70S
- 275Y
- 332K
- syn360G
- syn398E
syn70S
encoded from C210T, AGc->AGt
A/Catalonia/NS675 (2009-06-08) is the singular ΣPF11 peer.
332K
Novel to ΣPF11.
Progenitors may include:
H5N1 Avian Asia 2005, 2006, 2007, 2008
H6N1 Avian Europe 2005
H1N1 Swine 1977, 2002
H1N1 Seasonal 2007 (230I)
NCsw36883 (212E)
HKswNS1659
Iowa human swine worker 2005 H1N1 (IA/CEID23/2005)
syn360G
encoded from G1080A, GGg->GGa
Rare to ΣPF11 with 4 French instances in early pandemic.
Paris2590
Paris2591 (HA:225E)
Paris2592
Paris2604
Progenitors may include:
H1N1 Human North America 2007, Middle East 2006, 2007
H1N1 Avian North America 2006, 2007, 2008
H1N1 Avian Asia 2006
H1N1 Swine North America 1931, 2003, 2004, 2005, 2006
H1N1 Swine US 1931
H1N1 Swine Asia 1993, 2001, Europe 2001
H5N1 Avian North America 2005
H6N1 Avian North America 2007, Asia 2006
H10N1 Avian North America 2007
H11N1 Avian North America 2002
syn398E
encoded from G1194A, GAg->GAa
Rare to ΣPF11 with 7 instances.
Italy160 (July from Veneto)
Spain with 5 sequences as recently as 2009-10-28
Canada (May)
Progenitors unknown; however, a 12 residue span in this area, including residue 398, revises for WSN33 and H5N1 Human.
On Pavia21 TamiFlu Resistance is indicated in typical PF11 fashion via a Single Nucleotide Polymorphism coding for 275Y on the Neuraminidase. The sequence displays the following NA Quadruple Combination:
106I, 248D, 275Y, 286S
The following permutations are now represented on the thirteen PF11 anti-viral resistant sequences:
106V, 248N, 275Y, 286S = WA28, WA29, TX47
106I, 248N, 275Y, 286S = Osaka180
106I, 248D, 275Y, 286S = HK2369, Yamaguchi22, Denmark528, Hunan SWL3, Singapore57, Tokushima2, Iwate3, Quebec147365, Pavia21
Until the 2009-08-21 deposit of the two Washington sequences, all 275Y TamiFlu-Resistant specimens on PF11 backgrounds were paired with 106I. We continue to see only 3 of the 13 with 106V. The addition of Pavia21 heavily leverages position 248 toward Aspartate (D) with 9 specimens versus 4 with Asparagine (N). No TamiFlu Resistant specimen on file displays 286G as yet.
Pavia21 is the most hypermorphic TamiFlu-Resistant PF11 strain seen since the oddities from the immuno-compromised patients in Washington. Four changes other than H275Y is unusual in a single sequence.
We are quite impressed with the Influenza reservoir's ability to recycle data between serotypes without reassortment. Unless this sample were exposed to low level radiation during incubation, a series of accumulative recombinations have occurred over a very short time period or a triple co-infection enlisted all variants to build Pavia21 within a single host using an adaptation event to smooth the topping.
The most probable explanation is an accumulation of recombinations across the hypermorphic Catalonia region then exporting data to Italy via wild birds with a single co-incident adaptation event within the eventual host. Additionally, our team would not be at all surprised to find 225E on the HA of this patient's virus if the data is eventually published.
At any measure, another new background is now carrying TamiFlu Resistance in a central flyway for Influenza's primary transportation vector, wild birds.
2009-10-15
TamiFlu Resistance #12 from Canada, A/Quebec/147365, may drive Unique HA Polymorphism
The twelfth TamiFlu Resistant specimen with a publicly available sequence, A/Quebec/147365, was deposited today at GenBank with all 8 segments. We shall examine the primary antigens today, Segment 4 (HA) and Segment 6 (NA).
The antigen Hemagglutinin is of interest on this specimen due to the 259S introduction into ΣPF11. Antigens expressing novelty in areas that may affect Human Receptor Binding bear scrutiny. A second Quebec specimen today is an exact nucleotide match to the HA, A/Quebec/147023 HA. More important than the novelty and the prospect that the 259S change has spread is the fact that 98 other sequences in the reservoir are a 1700/1701 nucleotide match (99+%) with these two, offering a wide geography for future recombination:
You will recall that we've observed significant movement in the domain surrounding residue 259, including the boarding school cases with 259V in Jiangyin, 261V in Singapore, 263D in Tomsk, 264X in Jiangyin, 264S in TamiFlu Resistant WA29 and 264T in NY and Spain.
259S appears to be found only on Swine H1 from 2003 in two North Carolina samples (NCsw35279, NCsw36681) and does not feature on other previously banked H1N1 (human, avian), H3N2 (human, swine) or H5N1 (human, swine, avian). We may be looking at a series of in-situ, cross-segment Hemagglutinin genetic selections due to TamiFlu pressure, in addition to the H275Y on the Neuraminidase. We would suggest a careful examination of the samples at the Chinese boarding schools for sub-clonal minor populations carrying H275Y on the NA.
The NA of Quebec147365 is an exact amino acid match (469/469) with Denmark528, HK2369, Yamaguchi22, Hunan SWL3, Singapore57, Tokushima2 and Iwate3. Quebec147365 is also an exact nucleotide level match to Denmark528 and Iwate3.
On Quebec147365 TamiFlu Resistance is indicated in typical PF11 fashion via a Single Nucleotide Polymorphism coding for 275Y on the Neuraminidase. The sequence displays the following NA Quadruple Combination:
106I, 248D, 275Y, 286S
The following permutations are now represented on the twelve PF11 anti-viral resistant sequences:
106V, 248N, 275Y, 286S = WA28, WA29, TX47
106I, 248N, 275Y, 286S = Osaka180
106I, 248D, 275Y, 286S = HK2369, Yamaguchi22, Denmark528, Hunan SWL3, Singapore57, Tokushima2, Iwate3, Quebec147365
Until the 2009-08-21 deposit of the two Washington sequences, all 275Y TamiFlu-Resistant specimens on PF11 backgrounds were paired with 106I. We continue to see only 3 of the 11 with 106V.
The addition of Quebec147365 heavily leverages position 248 toward Aspartate (D) with 8 specimens versus 4 with Asparagine (N). No TamiFlu Resistant specimen on file displays 286G as yet.
The antigen Hemagglutinin is of interest on this specimen due to the 259S introduction into ΣPF11. Antigens expressing novelty in areas that may affect Human Receptor Binding bear scrutiny. A second Quebec specimen today is an exact nucleotide match to the HA, A/Quebec/147023 HA. More important than the novelty and the prospect that the 259S change has spread is the fact that 98 other sequences in the reservoir are a 1700/1701 nucleotide match (99+%) with these two, offering a wide geography for future recombination:
Geography | Sequence Count |
|
|
US (other) | 09 |
Canada | 04 |
Japan | 11 |
Taiwan | 01 |
Moscow | 03 |
Italy | 03 |
France | 01 |
Europe (other) | 04 |
South America | 03 |
You will recall that we've observed significant movement in the domain surrounding residue 259, including the boarding school cases with 259V in Jiangyin, 261V in Singapore, 263D in Tomsk, 264X in Jiangyin, 264S in TamiFlu Resistant WA29 and 264T in NY and Spain.
259S appears to be found only on Swine H1 from 2003 in two North Carolina samples (NCsw35279, NCsw36681) and does not feature on other previously banked H1N1 (human, avian), H3N2 (human, swine) or H5N1 (human, swine, avian). We may be looking at a series of in-situ, cross-segment Hemagglutinin genetic selections due to TamiFlu pressure, in addition to the H275Y on the Neuraminidase. We would suggest a careful examination of the samples at the Chinese boarding schools for sub-clonal minor populations carrying H275Y on the NA.
The NA of Quebec147365 is an exact amino acid match (469/469) with Denmark528, HK2369, Yamaguchi22, Hunan SWL3, Singapore57, Tokushima2 and Iwate3. Quebec147365 is also an exact nucleotide level match to Denmark528 and Iwate3.
On Quebec147365 TamiFlu Resistance is indicated in typical PF11 fashion via a Single Nucleotide Polymorphism coding for 275Y on the Neuraminidase. The sequence displays the following NA Quadruple Combination:
106I, 248D, 275Y, 286S
The following permutations are now represented on the twelve PF11 anti-viral resistant sequences:
106V, 248N, 275Y, 286S = WA28, WA29, TX47
106I, 248N, 275Y, 286S = Osaka180
106I, 248D, 275Y, 286S = HK2369, Yamaguchi22, Denmark528, Hunan SWL3, Singapore57, Tokushima2, Iwate3, Quebec147365
Until the 2009-08-21 deposit of the two Washington sequences, all 275Y TamiFlu-Resistant specimens on PF11 backgrounds were paired with 106I. We continue to see only 3 of the 11 with 106V.
The addition of Quebec147365 heavily leverages position 248 toward Aspartate (D) with 8 specimens versus 4 with Asparagine (N). No TamiFlu Resistant specimen on file displays 286G as yet.
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