Sequences discussed in this analysis are variously stored publicly at GenBank and at GISAID. We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GenBank and from GISAID’s EpiFlu™ Database on which this research is based. A GISAID-generated list is detailed in a linked spreadsheet for completeness in citation.
Last Update
2011-10-25
HA 142V appears on 22 pH1N1 human sequences geographically spanning 5 countries covering 16 cases documented from 2009-07-20 (Italy) to 2011-02-04 (Russia). Researchers produced multiple sequences for 5 cases. These 22 sequences delineate on the last day of 2010 from low polymorphic count genetics onto highly polymorphic Clade2: 188T backgrounds. The 9 most current HA 142V sequences share 6 HA revisions and 5 NA revisions demonstrating capable transmission.
At a minimum, 7 of those sequences represent fatalities. These fatality sequences were generated from 2 independent labs. The subjects were geographically dispersed (Nizhnii Novgorod and Vladimir: >100 miles distant). Non-fatality sequences (2) with HA 142V on similar Clade2 backgrounds are on file in a similar region of the world (Tula, Russia and Slovenia). Of 9 Clade2 sequences with HA 142V, 7 are noted as fatal (78% Case Fatality Rate). 5 of those 9 Clade2 sequences carry Receptor Binding Site revisions between HA aa225 and aa230, including 225G, 225N and 230I. Although the amino-level Ultimate Origin investigation for Valine at aa142 continues, many H5N1 sequences demonstrate the 2nd Base Codon donation potential (atg, ctt, ctg, ttg) to create the pH1N1 142V (GtT).
An examination of the Neuraminidase segments provides additional sectioning to the fatalities. The NA segments are hyper-morphic and zoonotic. Each Clade2 fatality with HA 142V carries NA syn204A. The 2 Clade2 non-fatality HA 142V-bearing sequences do not demonstrate the NA syn204A. All NA syn204A (GCa) pH1N1 sequences (7) are in cross-segment combination with HA 142V on a very common Clade2: 188T background.
Potential animal progenitors are found on 18 sequences in Avian and Mink hosts across several serotypes (H4N4, H5N4, H7N1, H8N4, H10N4). The databases do not yet appear to demonstrate NA syn204A (GCa) on an Avian H1N1 sequence. Future Avian H1N1 deposits may very well demonstrate that this value has crossed to human pH1N1 via an Avian H1N1 bridge (intermediate) from one of the noted H4N4, H5N4, H7N1, H8N4 or H10N4 serotypes.
7 human fatalities on 7 cases across 2 cities and 2 labs each bearing the rare HA 142V and the rarer NA syn204A merit attention as a potential “flashfire” candidate due to the 100% Case Fatality Rate (CFR) of this transmissible combination found on the most dominant pH1N1 Clade. Furthermore, this group of sequences demonstrates a superset of revisions (HA and NA) with significant homology to the Avian H1N1 pool. Each pH1N1 chimera strain that is in mid-stride between host species, that is “confused”, holds the potential for variant clinical symptoms and outcomes. Early detection of "flashfire" strains (High CFR) via increased surveillance is essential to public health planning.
Case Fatality Rates for HA 142V
44% CFR Overall (7 of 16)
78% CFR on Clade2 (2010-12-31 to 2011-02-14) (7 of 9)
78% CFR in Northern Hemisphere from 2010-12-31 to 2011-02-14 (7 of 9)
100% CFR with NA syn204A (7 of 7)
Hemagglutinin Statistics for HA 142V
Total HA: 123 Polymorphisms (2 to 14) on 22 HA Segments
. . . . . . . . with 30 Distinct Values
. . . . . . . . Averaging ~5.6 Polymorphisms per HA Segment
Total HA Clade2: 88 Polymorphisms (8 to 14) on 9 Segments
. . . . . . . . . . . . with 24 Distinct Values
. . . . . . . . . . . . Averaging ~9.8 Polymorphisms per Clade2 HA Segment
HA 142V is not found as a singleton polymorphism, even on short fragments. 100% of HA 142V-bearing pH1N1 human sequences (22) also carry either HA 188T (9), syn194L (12) or 225E (1, Origin pH1N1).
Neuraminidase Statistics for HA 142V
Total NA: 94 Polymorphisms (1 to 12) on 20 Segments
. . . . . . . . with 20 Distinct Values
. . . . . . . . Averaging ~4.7 Polymorphisms per HA Segment
Total NA Clade2: 81 Polymorphisms (7 to 12) on 9 Segments
. . . . . . . . . . . . with 19 Distinct Values
. . . . . . . . . . . . Averaging ~9.0 Polymorphisms per Clade2 NA Segment
100% of the available related NA segments (20) carries NA syn416D.
Clade2 Shared Polymorphisms
HA Background: 100N, 142V, 188T, syn338G, 377K, 454N (6 common)
NA Background: [76S (8), 77E (1)], syn240T, 241I, 369K, syn377P, syn416D (5 common)
Sequences
. . . . RussiaTulaCRIE_KEE_2011_02_04 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI335282
. . . . . . . . 10 Polymorphisms (5 Amino and 5 Silent)
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . syn154L (CTg) [Rare to pH1N1 Human (3 Total: 2 on Clade2)]
. . . . . . . . . . . . . . . . . . [H1N1 Avian Farm
. . . . . . . . . . . . . . . . . . . . . with #1T, syn202V
. . . . . . . . . . . . . . . . . . . . . . . . & extensive pH1N1υ polymorphisms],
. . . . . . . . . . . . . . . . . . [H1N1 swine],
. . . . . . . . . . . . . . . . . . [H7N7 Avian and Human (tcg)],
. . . . . . . . . . . . . . . . . . [H9N2 Avian 2009 & Human 2009
. . . . . . . . . . . . . . . . . . . . . with pH1N1υ polymorphisms],
. . . . . . . . . . . . . . . . . . [S9, M9, S7],
. . . . . . . . . . . . . . . . . . [WSN1933, WSZ1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . 188T,
. . . . . . . . syn202V (GTc) [H1N1 Avian Farm
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . . . . . . . . . . . [H6N1 Avian],
. . . . . . . . . . . . . . . . . . [S9],
. . . . . . . . . . . . . . . . . . [H1N1 Human 1943, 1946, 1951],
. . . . . . . . . . . . . . . . . . [WSN1933, WSZ1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn542S (TCc))
. . . . RussiaTulaCRIE_KEE_2011_02_04 (
. . . . . . . . GISAID NA EPI335288
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))
. . . . RussiaVladimirIIV35_T_27M_2011_01_31_f (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI324794
. . . . . . . . 14 Polymorphisms (10 Amino and 4 Silent)
. . . . . . . . 1T [42 pH1N1,
. . . . . . . . . . . . . only 9 from 2010-2011 Season (NH)],
. . . . . . . . . . [H1N1 Avian Farm
. . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . . . [H6N1 Avian (agc)]
. . . . . . . . . . [H7N7 Avian & Human Fatality],
. . . . . . . . . . [H9N2 Avian & Human (agc, agt, atc)],
. . . . . . . . . . [Netherlands2457b_2009_11_07_xL
. . . . . . . . . . . . . . . . . . with 225N,
. . . . . . . . . . IndiaHyderabad51_2009_05
. . . . . . . . . . . . . . . . . . with syn144A],
. . . . . . . . . . [H1N1 swine],
. . . . . . . . . . [S9, M9, S7],
. . . . . . . . . . [1976],
. . . . . . . . . . [WSN1933, WSZ1933],
. . . . . . . . . . [1918],
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . 157Q mix wt,
. . . . . . . . 188T,
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn515Q (CAa) [H5N1 Avian & Human wt],
. . . . . . . . syn527L (TTa) [H5N1 Avian])
. . . . RussiaVladimirIIV35_T_27M_2011_01_31_f (
. . . . . . . . GISAID NA EPI324795
. . . . . . . . 9 Polymorphisms (3 Amino and 6 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . syn204A (GCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn291V (GTa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))
. . . . RussiaNizhniiNovgorodCRIE_BLM_L_2011_01_26_TmX_f (
. . . . . . . . Clade2: 188T with 230I
. . . . . . . . GISAID HA EPI339320
. . . . . . . . 10 Polymorphisms (7 Amino and 3 Silent)
. . . . . . . . 77N [Recently Novel to Clade1.Upsilon],
. . . . . . . . . . . . [Emergent on pH1N1 Clade 1 (189T)
. . . . . . . . . . . . . . . . with 124N, 233H, 275A],
. . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . with syn42G, 159T,
. . . . . . . . . . . . . . . . . . . . 188T, 189T, syn346G, 453K],
. . . . . . . . . . . . [Rare to H1N1 US Swine with 124N (6)],
. . . . . . . . 100N,
. . . . . . . . 142V [H5N1 Avian (atg, ctg)],
. . . . . . . . 188T,
. . . . . . . . 230I (ATt) [H9N2 Avian & Human wt],
. . . . . . . . . . . . [H10N7 Avian 2008
. . . . . . . . . . . . . . . . with #1V, 87N, syn94Y, 100N, syn102E,
. . . . . . . . . . . . . . . . . . . 156E, 157E, 163T, 165N,
. . . . . . . . . . . . . . . . . . . syn177L, 188T, syn221P, syn207S, syn213F,
. . . . . . . . . . . . . . . . . . . 225G, 230I, 233H, 237I, syn239P,
. . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn356H,
. . . . . . . . . . . . . . . . . . . syn390N, syn391T],
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt) [H2 2009],
. . . . . . . . . . . . . . . . . . [H3N8 Canine 2007, Equine 2009, Swine],
. . . . . . . . . . . . . . . . . . [H5N1 wt],
. . . . . . . . . . . . . . . . . . [H5N2 Avian],
. . . . . . . . . . . . . . . . . . [H9N2 2009],
. . . . . . . . . . . . . . . . . . [H1N1 Avian 2010],
. . . . . . . . . . . . . . . . . . [H1N1 swine 2010],
. . . . . . . . syn542S (TCc) [H2, H5, H9N2],
. . . . . . . . . . . . . . . . . . [H1N1 Avian Farm
. . . . . . . . . . . . . . . . . . . . . with pH1N1υ polymorphisms])
. . . . RussiaNizhniiNovgorodCRIE_BLM_L_2011_01_26_TmX_f (
. . . . . . . . GISAID NA EPI339322
. . . . . . . . 10 Polymorphisms (4 Amino and 6 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . syn111K (AAa) [H1N1 Avian Farm],
. . . . . . . . syn204A (GCa),
. . . . . . . . syn240T (ACc) [H1N1 Avian Farm],
. . . . . . . . 241I [H1N1 Avian Farm],
. . . . . . . . 275Y mix wt,
. . . . . . . . 369K [H1N1 Avian
. . . . . . . . . . . . . . . . with syn111K, syn240T, 241I],
. . . . . . . . syn377P (CCa) [H5N1 Avian],
. . . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with 241I],
. . . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . exclusive of syn240T (ACc)],
. . . . . . . . syn416D (GAc) [H5N1 Avian Emergent 2011],
. . . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with syn51Q, syn240T, 241I],
. . . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with syn111K, syn377P])
. . . . RussiaNizhniiNovgorodCRIE_LAV_L_2011_01_24_f (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI335268
. . . . . . . . 9 Polymorphisms (6 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . 188T,
. . . . . . . . 225G,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn542S (TCc))
. . . . RussiaNizhniiNovgorodCRIE_LAV_L_2011_01_24_f (
. . . . . . . . GISAID NA EPI335295
. . . . . . . . 8 Polymorphisms (3 Amino and 5 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . syn204A (GCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))
. . . . RussiaNizhniiNovgorodCRIE_OAV_L_2011_01_24_f (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI335280
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn542S (TCc))
. . . . RussiaNizhniiNovgorodCRIE_OAV_L_2011_01_24_f (
. . . . . . . . GISAID NA EPI335294
. . . . . . . . 8 Polymorphisms (3 Amino and 5 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . syn204A (GCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))
. . . . RussiaNizhniiNovgorodCRIE_UBA_L_2011_01_23_f (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI335274
. . . . . . . . 12 Polymorphisms (9 Amino and 3 Silent)
. . . . . . . . 50I,
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . 188T,
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn542S (TCc))
. . . . RussiaNizhniiNovgorodCRIE_UBA_L_2011_01_23_f (
. . . . . . . . GISAID NA EPI335301
. . . . . . . . 12 Polymorphisms (5 Amino and 7 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 149F,
. . . . . . . . syn152R (AGa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . syn204A (GCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn291V (GTa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 305A,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))
. . . . Slovenia414_75F_2011_01_19 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI331063
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N,
. . . . . . . . syn467C (TGt) mix wt [H1N1 Avian Farm])
. . . . Slovenia414_75F_2011_01_19 (
. . . . . . . . GISAID NA EPI331064
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . 77E [H1N1 Avian],
. . . . . . . . syn162P (CCc) [H1N1 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 242I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))
. . . . RussiaNizhniiNovgorodCRIE_PAV_L_2011_01_10_f (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI339341
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn542S (TCc))
. . . . RussiaNizhniiNovgorodCRIE_PAV_L_2011_01_10_f (
. . . . . . . . GISAID NA EPI339342
. . . . . . . . 10 Polymorphisms (5 Amino and 5 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 115L,
. . . . . . . . syn204A (GCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 322L [H1N1 Avian with syn240T, 241I],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))
. . . . RussiaNizhniiNovgorodCRIE_NGV_L_2010_12_31_f (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI339312
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn542S (TCc))
. . . . RussiaNizhniiNovgorodCRIE_NGV_L_2010_12_31_f (
. . . . . . . . GISAID NA EPI339314
. . . . . . . . 9 Polymorphisms (4 Amino and 5 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 115L,
. . . . . . . . syn204A (GCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))
. . . . Moldova93_CS_2010_01_05 (
. . . . . . . . GISAID HA EPI278150
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . 324I (aTC) [H1N1 Avian],
. . . . . . . . . . . . . . [H3N2 Avian with 159S],
. . . . . . . . . . . . . . [H3N2 Canine with syn287G],
. . . . . . . . . . . . . . [H3N8 Avian Emergent],
. . . . . . . . . . . . . . [H6 Avian],
. . . . . . . . . . . . . . [S8],
. . . . . . . . HA Truncated after aa396)
. . . . Moldova93_CS_2010_01_05 (
. . . . . . . . GISAID NA EPI278149
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . syn416D (GAc))
. . . . KazakhstanTaraz01_2009_12 (
. . . . . . . . GISAID HA EPI235349
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 4Y,
. . . . . . . . syn111V (GTa) [H1N1 Avian],
. . . . . . . . . . . . . . . . [H9N2 Human (Gca)],
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . 225G,
. . . . . . . . 324I (aTC) [H1N1 Avian],
. . . . . . . . . . . . . . [H3N2 Avian with 159S],
. . . . . . . . . . . . . . [H3N2 Canine with syn287G],
. . . . . . . . . . . . . . [H3N8 Avian Emergent],
. . . . . . . . . . . . . . [H6 Avian],
. . . . . . . . . . . . . . [S8])
. . . . KazakhstanAlmaty373_9M_2009_11_28 (
. . . . . . . . GISAID HA EPI277103
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)
. . . . KazakhstanAlmaty373M_9M_2009_11_28 (
. . . . . . . . GISAID NA EPI277104
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa193,
. . . . . . . . syn416D (GAc))
. . . . KazakhstanAlmaty373CX_9M_2009_11_28 (
. . . . . . . . GISAID HA EPI271067
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)
. . . . KazakhstanAlmaty373CX_9M_2009_11_28 (
. . . . . . . . GISAID NA EPI271068
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa193,
. . . . . . . . syn416D (GAc))
. . . . KazakhstanAlmaty352M_9M_2009_11_23 (
. . . . . . . . GISAID HA EPI277101
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)
. . . . KazakhstanAlmaty352M_9M_2009_11_23 (
. . . . . . . . GISAID NA EPI277102
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa184,
. . . . . . . . syn416D (GAc))
. . . . KazakhstanAlmaty352CX_9M_2009_11_23 (
. . . . . . . . GISAID HA EPI271065
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)
. . . . KazakhstanAlmaty352CX_9M_2009_11_23 (
. . . . . . . . GISAID NA EPI271066
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa184,
. . . . . . . . syn416D (GAc))
. . . . KazakhstanAlmaty347M_18M_2009_11_19 (
. . . . . . . . GISAID HA EPI277098
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . 124I [H1N1 Avian],
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)
. . . . KazakhstanAlmaty347M_18M_2009_11_19 (
. . . . . . . . GISAID NA EPI277099
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa184,
. . . . . . . . syn416D (GAc))
. . . . KazakhstanAlmaty347_NP_18M_2009_11_19 (
. . . . . . . . GISAID HA EPI277097
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . 124I [H1N1 Avian],
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)
. . . . KazakhstanAlmaty347_NP_18M_2009_11_19 (
. . . . . . . . GISAID NA EPI277100
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa184,
. . . . . . . . syn416D (GAc))
. . . . KazakhstanAlmaty347CX_18M_2009_11_19 (
. . . . . . . . GISAID HA EPI271063
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . 124I [H1N1 Avian],
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)
. . . . KazakhstanAlmaty347CX_18M_2009_11_19 (
. . . . . . . . GISAID NA EPI271064
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa184,
. . . . . . . . syn416D (GAc))
. . . . KazakhstanAlmaty347_18M_2009_11_19 (
. . . . . . . . GISAID HA EPI271061
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . 124I [H1N1 Avian],
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)
. . . . KazakhstanAlmaty347_18M_2009_11_19 (
. . . . . . . . GISAID NA EPI271062
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa184,
. . . . . . . . syn416D (GAc))
. . . . KazakhstanAlmaty330_NP_4M_2009_11_17 (
. . . . . . . . GISAID HA EPI277095
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)
. . . . KazakhstanAlmaty330_NP_4M_2009_11_17 (
. . . . . . . . GISAID NA EPI277096
. . . . . . . . 2 Polymorphisms (0 Amino and 2 Silent)
. . . . . . . . NA Truncated before aa186,
. . . . . . . . syn259E (GAg)[H1N1 Avian],
. . . . . . . . syn416D (GAc))
. . . . KazakhstanAlmaty330_4M_2009_11_17 (
. . . . . . . . GISAID HA EPI271059
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)
. . . . KazakhstanAlmaty330_4M_2009_11_17 (
. . . . . . . . GISAID NA EPI271060
. . . . . . . . 2 Polymorphisms (0 Amino and 2 Silent)
. . . . . . . . NA Truncated before aa186,
. . . . . . . . syn259E (GAg) [H1N1 Avian],
. . . . . . . . syn416D (GAc))
. . . . ItalyPavia15_2009_07_20 (
. . . . . . . . GISAID HA EPI240761
. . . . . . . . 2 Polymorphisms (2 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa83,
. . . . . . . . 142V,
. . . . . . . . 225E,
. . . . . . . . HA Truncated after aa338)
Showing posts with label cross segment linkage. Show all posts
Showing posts with label cross segment linkage. Show all posts
2010-11-02
HA 230I with 225N Demonstrated in Iowa Swine during November 2009
Last Updated 2010-11-08
On 2010-11-01, a collaboration of researchers based in Ames, Iowa deposited a swine sequence at GenBank. November 2009 is the sample month, approximately one year prior to publication. The first instance of the dual RBD change 225N and 230I is found in this swine data.
Though the HA is hyper-morphic, the cross-linked Iowa swine has only one NA change (syn414G) other than the cross-linkage syn407V for a total of 2 silent changes. Those two changes on the NA appear only in a single pandemic sequence, Liaoning_HepingSWL1606_13M_2009_12_23. The two changes (syn407V with syn414G) also appear in 16 recent H5N1 (2006-2009) sequences: 2 human, 10 birds and 4 environmental.
The potential HA recombinant appears to be on a pandemic H1N1 background with multiple donation bases from S7 H1N1 and S7 & S5 H1N2 including several blocks coding for contiguous amino acid revision. The swine HA sequence has 92% homology to the nearest HA. More than 100 changes are demonstrated on the swine HA, the bulk of which appear on Seasonal H1N1 2007.
swIowa44837_1_2009_11_08_xL carries a universe of changes suggestive as a progenitor of / donor to the recently discussed emergence of a 230I-permissive sub-clade. The swine matches and domaining are evident around several of the six markers for the new sub-clade as well as around several non-marker polymorphisms from the emerging sub-clade sequences.
Furthermore, this single swine sequence also carries markers implicated in the cross-linked Russian fatality analysis. An annotated chart was developed to investigate the various paths to fatality in Russia, determining that high genetic lability existed for fatal outcomes and that changes at amino acid 225 were not required to produce fatal outcomes. The group of fatal sequences from Moscow and Ivanovo in the bottom right of the annotated phylogenetic tree carries a large number of changes including the syn355H found on the swine sequence under review in this analysis. The opposed group of fatal sequences from Ulyanovsk in the top left of the chart carries the smallest count of changes from the larger deposit and includes the syn372Q found on swIowa44837_1_2009_11_08_xL.
Similar sequences to this Iowa swine recombinant have been recorded circulating throughout the United States in Minnesota, North Carolina, Illinois and Indiana during late 2009 and early 2010 including:
swMinnesota02979_2010_02_17
swMinnesota02976_2010_01_12
swIllinois3910_2010_01_11
swIllinois02957_2010
swIllinois02960_2010
swIllinois02938_2009-12-29
swIllinois02935_2009_12_20
swIllinois02936_2009_12_20
swIllinois02919_2009_11_12
swIllinois32975_2009_11_11
swNorthCarolina02926_2009_11_24
swIndiana27007_2009
. . . . swIowa44837_1_2009_11_08_xL (
. . . . . . . . Hyper-morphic HA recombinant on PF11 background
. . . . . . . . with multiple donation bases from S7 H1N1 and S7 & S5 H1N2:
. . . . . . . . ~ 92% Homology to nearest HA
. . . . . . . . with more than 100 changes including, but not limited to:
. . . . . . . . syn36L,
. . . . . . . . syn38E,
. . . . . . . . syn40H,
. . . . . . . . syn41N,
. . . . . . . . syn42G,
. . . . . . . . 48K [S7],
. . . . . . . . syn49G,
. . . . . . . . 50I [S7],
. . . . . . . . syn56G, syn58C, syn70C, syn86S, 92M,
. . . . . . . . 131S,
. . . . . . . . 132T [S7],
. . . . . . . . 156E [swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn169I, syn170N, 171E,
. . . . . . . . 182V [S7],
. . . . . . . . . . . . . [NY7480_2010_03_01 with 253A],
. . . . . . . . 188R,
. . . . . . . . 189G [S7],
. . . . . . . . 193G,
. . . . . . . . 196H [S7],
. . . . . . . . 197H,
. . . . . . . . 198E [S7],
. . . . . . . . 199N [S7],
. . . . . . . . 214T [S7],
. . . . . . . . syn222K [S7],
. . . . . . . . syn224R [S7],
. . . . . . . . 225N [swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn226Q [S7],
. . . . . . . . syn228G [S7],
. . . . . . . . 230I [S7],
. . . . . . . . syn232Y [S7],
. . . . . . . . syn235T [S7],
. . . . . . . . 238D [H2N3, H7N3, H7N7, tn, swine],
. . . . . . . . . . . . . [RussiaBelgorod2_2010_03_15
. . . . . . . . . . . . . . . . . . with 158E, 225G, 230I],
. . . . . . . . 241Y,
. . . . . . . . 244I [S7],
. . . . . . . . syn246E [S7],
. . . . . . . . . . . . . . . [TexasAF2579_2009_10_04 with 230I],
. . . . . . . . 248N,
. . . . . . . . syn251L,
. . . . . . . . 253A [NY7480_2010_03_01 with 182V],
. . . . . . . . 260L [S7],
. . . . . . . . 263G,
. . . . . . . . 264F [S7],
. . . . . . . . 272N [S7],
. . . . . . . . 273A [S7],
. . . . . . . . 275M [S7],
. . . . . . . . 276G,
. . . . . . . . 277E [S7],
. . . . . . . . 280A [MI09_2007_H1N2],
. . . . . . . . 281N,
. . . . . . . . 298V [S7],
. . . . . . . . 305E [swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn329S [S7],
. . . . . . . . syn346G [S7],
. . . . . . . . . . . . . . . [H3N2, H3N8, H5N1, H6N2, H6N4, H10N7],
. . . . . . . . . . . . . . [Fixed in non-PF11 Emergent swine lineages,
. . . . . . . . . . . . . . swNC19646_2010_04_20 with 158E,
. . . . . . . . . . . . . . Minnesota04_2010_03_22 with 230I,
. . . . . . . . . . . . . . Nevada01_2010_01_02,
. . . . . . . . . . . . . . Nevada20_2009_12_03,
. . . . . . . . . . . . . . Sachsen180_2009_12_02,
. . . . . . . . . . . . . . Lisboa108_2009_11_30 with 225E, syn228G,
. . . . . . . . . . . . . . GhanaFS2206_2009_11_25 with syn228G,
. . . . . . . . . . . . . . GhanaFS1982_2009_11_16 with syn228G,
. . . . . . . . . . . . . . NewMexico16MXC1_2009_11_07,
. . . . . . . . . . . . . . BZ_RioJaneiro7131_2009_08_01_f],
. . . . . . . . syn355H [MI09_2007_H1N2,
. . . . . . . . . . . . . . . . swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn361G [S7],
. . . . . . . . syn372Q [S7],
. . . . . . . . 376N [MI09_2007_H1N2,
. . . . . . . . . . . . swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn379T [S7],
. . . . . . . . . . . . . . . [Wisconsin06_2010_04_28],
. . . . . . . . syn381K [S7],
. . . . . . . . syn382V [S7],
. . . . . . . . syn385V [S7],
. . . . . . . . syn388K [S7],
. . . . . . . . syn390N [S7],
. . . . . . . . . . . . . . . [H2, H3N8, H5, H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . . . . . . . . [Calif09_2010_05_11],
. . . . . . . . syn391T [S7],
. . . . . . . . syn392Q [S7],
. . . . . . . . syn395A [S7],
. . . . . . . . syn396V [S7],
. . . . . . . . syn397G [S7],
. . . . . . . . syn399E [S7],
. . . . . . . . . . . . . . . [Arizona06_2010_05_29 with 158E],
. . . . . . . . syn403L [S7],
. . . . . . . . 405R [S7],
. . . . . . . . 407M [S7],
. . . . . . . . syn413K [S7],
. . . . . . . . syn419L [S7],
. . . . . . . . syn428L [S7],
. . . . . . . . syn443S [S7],
. . . . . . . . syn495E [MI09_2007_H1N2],
. . . . . . . . 508R,
. . . . . . . . syn515Q)
On 2010-11-01, a collaboration of researchers based in Ames, Iowa deposited a swine sequence at GenBank. November 2009 is the sample month, approximately one year prior to publication. The first instance of the dual RBD change 225N and 230I is found in this swine data.
Though the HA is hyper-morphic, the cross-linked Iowa swine has only one NA change (syn414G) other than the cross-linkage syn407V for a total of 2 silent changes. Those two changes on the NA appear only in a single pandemic sequence, Liaoning_HepingSWL1606_13M_2009_12_23. The two changes (syn407V with syn414G) also appear in 16 recent H5N1 (2006-2009) sequences: 2 human, 10 birds and 4 environmental.
The potential HA recombinant appears to be on a pandemic H1N1 background with multiple donation bases from S7 H1N1 and S7 & S5 H1N2 including several blocks coding for contiguous amino acid revision. The swine HA sequence has 92% homology to the nearest HA. More than 100 changes are demonstrated on the swine HA, the bulk of which appear on Seasonal H1N1 2007.
swIowa44837_1_2009_11_08_xL carries a universe of changes suggestive as a progenitor of / donor to the recently discussed emergence of a 230I-permissive sub-clade. The swine matches and domaining are evident around several of the six markers for the new sub-clade as well as around several non-marker polymorphisms from the emerging sub-clade sequences.
Furthermore, this single swine sequence also carries markers implicated in the cross-linked Russian fatality analysis. An annotated chart was developed to investigate the various paths to fatality in Russia, determining that high genetic lability existed for fatal outcomes and that changes at amino acid 225 were not required to produce fatal outcomes. The group of fatal sequences from Moscow and Ivanovo in the bottom right of the annotated phylogenetic tree carries a large number of changes including the syn355H found on the swine sequence under review in this analysis. The opposed group of fatal sequences from Ulyanovsk in the top left of the chart carries the smallest count of changes from the larger deposit and includes the syn372Q found on swIowa44837_1_2009_11_08_xL.
Similar sequences to this Iowa swine recombinant have been recorded circulating throughout the United States in Minnesota, North Carolina, Illinois and Indiana during late 2009 and early 2010 including:
swMinnesota02979_2010_02_17
swMinnesota02976_2010_01_12
swIllinois3910_2010_01_11
swIllinois02957_2010
swIllinois02960_2010
swIllinois02938_2009-12-29
swIllinois02935_2009_12_20
swIllinois02936_2009_12_20
swIllinois02919_2009_11_12
swIllinois32975_2009_11_11
swNorthCarolina02926_2009_11_24
swIndiana27007_2009
. . . . swIowa44837_1_2009_11_08_xL (
. . . . . . . . Hyper-morphic HA recombinant on PF11 background
. . . . . . . . with multiple donation bases from S7 H1N1 and S7 & S5 H1N2:
. . . . . . . . ~ 92% Homology to nearest HA
. . . . . . . . with more than 100 changes including, but not limited to:
. . . . . . . . syn36L,
. . . . . . . . syn38E,
. . . . . . . . syn40H,
. . . . . . . . syn41N,
. . . . . . . . syn42G,
. . . . . . . . 48K [S7],
. . . . . . . . syn49G,
. . . . . . . . 50I [S7],
. . . . . . . . syn56G, syn58C, syn70C, syn86S, 92M,
. . . . . . . . 131S,
. . . . . . . . 132T [S7],
. . . . . . . . 156E [swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn169I, syn170N, 171E,
. . . . . . . . 182V [S7],
. . . . . . . . . . . . . [NY7480_2010_03_01 with 253A],
. . . . . . . . 188R,
. . . . . . . . 189G [S7],
. . . . . . . . 193G,
. . . . . . . . 196H [S7],
. . . . . . . . 197H,
. . . . . . . . 198E [S7],
. . . . . . . . 199N [S7],
. . . . . . . . 214T [S7],
. . . . . . . . syn222K [S7],
. . . . . . . . syn224R [S7],
. . . . . . . . 225N [swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn226Q [S7],
. . . . . . . . syn228G [S7],
. . . . . . . . 230I [S7],
. . . . . . . . syn232Y [S7],
. . . . . . . . syn235T [S7],
. . . . . . . . 238D [H2N3, H7N3, H7N7, tn, swine],
. . . . . . . . . . . . . [RussiaBelgorod2_2010_03_15
. . . . . . . . . . . . . . . . . . with 158E, 225G, 230I],
. . . . . . . . 241Y,
. . . . . . . . 244I [S7],
. . . . . . . . syn246E [S7],
. . . . . . . . . . . . . . . [TexasAF2579_2009_10_04 with 230I],
. . . . . . . . 248N,
. . . . . . . . syn251L,
. . . . . . . . 253A [NY7480_2010_03_01 with 182V],
. . . . . . . . 260L [S7],
. . . . . . . . 263G,
. . . . . . . . 264F [S7],
. . . . . . . . 272N [S7],
. . . . . . . . 273A [S7],
. . . . . . . . 275M [S7],
. . . . . . . . 276G,
. . . . . . . . 277E [S7],
. . . . . . . . 280A [MI09_2007_H1N2],
. . . . . . . . 281N,
. . . . . . . . 298V [S7],
. . . . . . . . 305E [swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn329S [S7],
. . . . . . . . syn346G [S7],
. . . . . . . . . . . . . . . [H3N2, H3N8, H5N1, H6N2, H6N4, H10N7],
. . . . . . . . . . . . . . [Fixed in non-PF11 Emergent swine lineages,
. . . . . . . . . . . . . . swNC19646_2010_04_20 with 158E,
. . . . . . . . . . . . . . Minnesota04_2010_03_22 with 230I,
. . . . . . . . . . . . . . Nevada01_2010_01_02,
. . . . . . . . . . . . . . Nevada20_2009_12_03,
. . . . . . . . . . . . . . Sachsen180_2009_12_02,
. . . . . . . . . . . . . . Lisboa108_2009_11_30 with 225E, syn228G,
. . . . . . . . . . . . . . GhanaFS2206_2009_11_25 with syn228G,
. . . . . . . . . . . . . . GhanaFS1982_2009_11_16 with syn228G,
. . . . . . . . . . . . . . NewMexico16MXC1_2009_11_07,
. . . . . . . . . . . . . . BZ_RioJaneiro7131_2009_08_01_f],
. . . . . . . . syn355H [MI09_2007_H1N2,
. . . . . . . . . . . . . . . . swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn361G [S7],
. . . . . . . . syn372Q [S7],
. . . . . . . . 376N [MI09_2007_H1N2,
. . . . . . . . . . . . swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn379T [S7],
. . . . . . . . . . . . . . . [Wisconsin06_2010_04_28],
. . . . . . . . syn381K [S7],
. . . . . . . . syn382V [S7],
. . . . . . . . syn385V [S7],
. . . . . . . . syn388K [S7],
. . . . . . . . syn390N [S7],
. . . . . . . . . . . . . . . [H2, H3N8, H5, H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . . . . . . . . [Calif09_2010_05_11],
. . . . . . . . syn391T [S7],
. . . . . . . . syn392Q [S7],
. . . . . . . . syn395A [S7],
. . . . . . . . syn396V [S7],
. . . . . . . . syn397G [S7],
. . . . . . . . syn399E [S7],
. . . . . . . . . . . . . . . [Arizona06_2010_05_29 with 158E],
. . . . . . . . syn403L [S7],
. . . . . . . . 405R [S7],
. . . . . . . . 407M [S7],
. . . . . . . . syn413K [S7],
. . . . . . . . syn419L [S7],
. . . . . . . . syn428L [S7],
. . . . . . . . syn443S [S7],
. . . . . . . . syn495E [MI09_2007_H1N2],
. . . . . . . . 508R,
. . . . . . . . syn515Q)
2010-07-04
93% Human Fatality Rate in Russia Driven by Silent Pandemic Flu Markers
Sages have long said that brevity is the soul of wit.
But wit may not be fashioned in all occasions. Russian honesty this month provided us with a glancing blow. You know the type of impact . . . the one that brings an instant of reflection, a moment of dread and then the pause where clarity imbues the many loose associations and suddenly a fabric is woven? If we've done our job of transforming the raw data into information, you'll be able to see the pattern after reviewing this study a few times.
Therefore, today, we dispense with wit. Brevity will likely leave us as well. If brevity must be excused from this discussion, then a replacement must be located.
Let’s consider density for a moment. For this exercise, we think that density must suffice. As density increases, particles arrive at closer proximity to each other. Critical mass may be achieved. In the infectious disease world, proximity drives multiplicity of exposure and variation occurs. The ΣPF11 reservoir (pH1N1) has already shown expertise as a master of improvisation with revision at 100% of the residues in one critical HA area.
In this matter, particles are most certainly compressing and coalescing as you will see in the data deposited on 2010-06-01 from Russia. 77 sequences were produced, but only 27 were investigational candidates, offering the HA and NA gene segments in sufficient depth to conduct a full-scale analysis concerning the correlation between our predicted cross-linkage background and negative clinical outcomes.
The cross-linkage of the silent HA 413K and the silent NA 407V polymorphisms appears to be a strong predictor of fatality. Cross-Linking may also be indicative of avian inroads onto the human sequence, driving Influenza Flux and the Hydra Effect. In November 2009, the pH1N1 sequence database at GenBank showed that less than one-half of one percent was cross-linked. As predicted and documented, the cross-linked background has been increasing in density around the world since the spark was initially categorised during October and November in the Ukraine.
In developed areas of the world with a significant devotion to observational science, data surveillance allows factual insight for ΣPF11 moving more deeply into bird flu territory. Three countries have provided useful data to this point: Germany, the Netherlands and Russia.
The recent percentages indicate a significant sub-clading involving cross-linkage. German cases demonstrated a 23% cross-linkage rate in a 2010-04-15 deposit of 99 sequences. The Netherlands showed a 53% rate through a 2010-06-29 deposit. Russia, however, confirmed and re-leveled the concept with strong numbers and substantial allied clinical data. Great appreciation must be expressed to the labs in Russia who conduct such dutiful and comprehensive surveillance. The world benefits from data transparency.
A proper dataset was derived by examining the 20 Russian cases from the month of November that provided the required HA and NA sections for cross-segment analysis. The data is reasonably varied on several axes. The sequences were sampled in a range from November 2 to November 30, span 12 distinct geographies and include cases from locales with previous deposits (useful in comparative delta studies). 15 of the 20 sequences demonstrate cross-linking. With Russia calculating to 75% cross-linking, a new threshold is established.
Cross-Linkage Percentage
An increase from 0.5% to 75% draws the eye for further analysis and the sequences tell the truth. 14 of the cross-linked sequences from November in this Russian deposit are confirmed fatalities. 93% of the humans carrying these two "silent" genetic markers died of pandemic influenza. Only 9 of those cases showed a change at amino acid position 225, suggesting that revision at position 225 is not required for expiration, though the combination with cross-linkage suggests increased virulence. The synonymous pairing of HA 413K and NA 407V represents a strong correlation at this point to fatal human cases of pH1N1.
Bear in mind that the United States may lead the world in cross-linkages cases. The count of examined cases is clearly equal to Russia, but more importantly, the partial sequences on file show a strong pattern that cannot be validated or denied due to baffling truncations of data. Western Europe is at significant risk as Spain is currently inundated with these markers and may have been an early donation source to the Ukraine. Other European countries on the wild bird migration FlightPath (Italy and Greece) also pattern the truncations of data that disallow proper validation.
The greater portion of revisions found on these fatal Russian cross-linked sequences share homology with known zoonotic Influenza reservoirs. Most of the cross-linked sequences are hyper-morphic. 95 polymorphisms among only 15 November sequences solve for an average 6.33 changes per cross-linked HA. Three of the HA sequences have 8 revisions and only one has less than 5 polymorphisms. Ulyanovsk_KLA_2009_11_13_xL_f with only 3 changes (all “silent”) was, nonetheless, fatal to the person infected.
Phylogenentic analysis demonstrates significant genetic diversity within this set of cross-linked sequences. The unrooted tree of all 19 xL cases in this deposit (Figure A including pre- and post-November) provides leafing evidence of wide variation. This wide variation suggests an ease of syn413K recombination across multiple disparate pathways or, in a logic reversal, that HA syn413K / NA syn407V may act as a catalyst for increased and varied genetic acquisitions.
Figure A: Tree of Russian Cross-Linked Sequences from 2010-06-01 Deposit
The PF11 background is primed for zoonotic inclusions due to the present wild type homology with recognised avian sources at 138A, 194L, 226Q and 228G. Perhaps the syn413K completes some odd biological circuit with these recognised Avian markers in PF11, allowing a surge of acquisitions. The ongoing presence of the Avian 225G throughout the world signals five of the six Avian differentiation polymorphic locations are habitually found in this human pandemic reservoir. 190E, the sixth and final Avian revision area from the 2000-06 joint study on early pandemic RBD alterations has been predicted for PF11, but not yet publicly documented due to data sparsity and lab procedures that bias sequence output.
The following two annotated phylogenetic trees suggest that the xL background is magnetized for changes at 225. For simplicity of illustration, the first annotated tree (Figure B) reviews a set of three triples. Each triple set has one xL sequence with wild type 225 and two Russian sequences related by homology, one each with 225G and 225N. Revision at 225 occurs with great facility on this background.
Figure B: Tree of 3 Selected xL sequences & related Russian cases
The second annotated tree (Figure C) expands an early branch of Figure B, demonstrating the diversity and penetration of the syn177L, 324I, syn413K, syn542S grouping. The manifestation of three additional 225G strains (Ivanovo_AIV, Ivanovo_BOV, MoscowOb_OAM) at this early branch does not appear random, but is indicative that parallel patterns of accumulation are occurring across backgrounds with the silent HA 413K polymorphism.
Figure C: Tree of 3 Selected xL sequences & related Russian cases, expanded
Furthermore, these polymorphisms that have accumulated onto the sequences in Russia align with non-human Influenza reservoirs such as wild birds, domestic food poultry (chickens and turkeys), domestic pets (cats and dogs) and in equines used for racing (horse) and agriculture (donkey).
H5N1, H3N8, H7N7 and H9N2 feature prominently.
The sequence details provide case location, date of sample, indication of cross-linkage (_xL), indication of fatality (_f) and a color coding marking the samples bearing HA 225G. None of these November xL sequences carry the more virulent HA 225N, though 3 homology-related fatal 225N sequences are found in the larger Russia 2010-06-01 deposit. Polymorphisms followed by brackets demonstrate the listing of non-human Influenza serotypes that carry instances of the particular change.
Sometimes density is required for understanding. The truth is in the sequences.
Ivanovo_AMV_2009_11_xL_f (
. . . . syn177L [H3N8, H6, H7N7],
. . . . 225G mix,
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Kaluga_INV_2009_11_xL _f (
. . . . 225G mix,
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . 491E [H11],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
MoscowOb_DEI_2009_11_xL_f (
. . . . syn177L [H3N8, H6, H7N7],
. . . . 225G,
. . . . syn310V [H3N8, H5N1 (E/A/H), H6, H7N7, H11],
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
MoscowOb_OAM_2009_11_02_xL_f (
. . . . syn177L [H3N8, H6, H7N7],
. . . . syn205G [H6, H7N7],
. . . . 225G,
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Lipetsk_BVV_2009_11_10_xL_f (
. . . . syn177L [H3N8, H6, H7N7],
. . . . 225G mix,
. . . . syn238E [H2, H4],
. . . . syn240G [H3N8, H6, H9N2, H11],
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Ulyanovsk_KLA_2009_11_13_xL_f (
. . . . syn372Q [H2, H3N8, H4, H5, H6, H7N3, H7N7, H9N2, H11],
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Stavropol_BLV_2009_11_18_xL (
. . . . syn6L [H3N8],
. . . . 19I [H3N8],
. . . . syn177L [H3N8, H6, H7N7],
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Moscow_CHSN_2009_11_23_xL_f (
. . . . syn177L [H3N8, H6, H7N7],
. . . . 225G,
. . . . 324I,
. . . . syn376D [H2, H3N8, H4, H5, H6, H7N3, H7N7, H9N2, H11],
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn484N [H3N8, H4, H5N1 (E/A/H), H6, H7N7, H9N2, H11]),
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
MoscowOb_KMA_2009_11_23_xL_f (
. . . . 38G [H3N8],
. . . . 225G mix,
. . . . 264T,
. . . . 324I,
. . . . 491E [H11],
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Astrakhan_CHRM_2009_11_24_xL_f (
. . . . syn71E [H6N1],
. . . . syn109S [H2, H3N8, H9N2, H11],
. . . . syn177L [H3N8, H6, H7N7],
. . . . syn214K [H9N2],
. . . . 324I,
. . . . syn355H [H2, H5N1, H6N1],
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Ivanovo_RNA_2009_11_24_xL_f (
. . . . 0I,
. . . . syn168Y [H9N2],
. . . . 225G/225N/225D wt,
. . . . 269V [H9N2, H11],
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn426A [H2, H4, H5, H6, H7N7, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
MoscowOb_ZNF_2009_11_24_xL_f (
. . . . syn71E [H6N1],
. . . . syn109S [H2, H3N8, H9N2, H11],
. . . . syn177L [H3N8, H6, H7N7],
. . . . 324I,
. . . . syn331G [H3N8, H4, H6, H7N3, H7N7, H11]
. . . . syn355H [H2, H5N1, H6N1],
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Arkhangelsk_GNY_2009_11_25_xL_f (
. . . . syn134G [H2, H3N8, H4, H5N1 (E/A/H), H6, H9N2, H11],
. . . . syn177L [H3N8, H6, H7N7],
. . . . syn238E [H2, H4],
. . . . syn240G [H3N8, H6, H9N2, H11],
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . 437N,
. . . . syn484N [H3N8, H4, H5N1 (E/A/H), H6, H7N7, H9N2, H11])
HA and NA
Ivanovo_KOE_2009_11_25_xL_f (
. . . . syn177L [H3N8, H6, H7N7],
. . . . syn310V [H3N8, H5N1 (E/A/H), H6, H7N7, H11],
. . . . 324I,
. . . . syn359E [H5, H7N7, H11],
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Tambov_LLA_2009_11_30_xL_f (
. . . . syn177L [H3N8, H6, H7N7],
. . . . 225G/225N/225D wt,
. . . . syn310V [H3N8, H5N1 (E/A/H), H6, H7N7, H11],
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
But wit may not be fashioned in all occasions. Russian honesty this month provided us with a glancing blow. You know the type of impact . . . the one that brings an instant of reflection, a moment of dread and then the pause where clarity imbues the many loose associations and suddenly a fabric is woven? If we've done our job of transforming the raw data into information, you'll be able to see the pattern after reviewing this study a few times.
Therefore, today, we dispense with wit. Brevity will likely leave us as well. If brevity must be excused from this discussion, then a replacement must be located.
Let’s consider density for a moment. For this exercise, we think that density must suffice. As density increases, particles arrive at closer proximity to each other. Critical mass may be achieved. In the infectious disease world, proximity drives multiplicity of exposure and variation occurs. The ΣPF11 reservoir (pH1N1) has already shown expertise as a master of improvisation with revision at 100% of the residues in one critical HA area.
In this matter, particles are most certainly compressing and coalescing as you will see in the data deposited on 2010-06-01 from Russia. 77 sequences were produced, but only 27 were investigational candidates, offering the HA and NA gene segments in sufficient depth to conduct a full-scale analysis concerning the correlation between our predicted cross-linkage background and negative clinical outcomes.
The cross-linkage of the silent HA 413K and the silent NA 407V polymorphisms appears to be a strong predictor of fatality. Cross-Linking may also be indicative of avian inroads onto the human sequence, driving Influenza Flux and the Hydra Effect. In November 2009, the pH1N1 sequence database at GenBank showed that less than one-half of one percent was cross-linked. As predicted and documented, the cross-linked background has been increasing in density around the world since the spark was initially categorised during October and November in the Ukraine.
In developed areas of the world with a significant devotion to observational science, data surveillance allows factual insight for ΣPF11 moving more deeply into bird flu territory. Three countries have provided useful data to this point: Germany, the Netherlands and Russia.
The recent percentages indicate a significant sub-clading involving cross-linkage. German cases demonstrated a 23% cross-linkage rate in a 2010-04-15 deposit of 99 sequences. The Netherlands showed a 53% rate through a 2010-06-29 deposit. Russia, however, confirmed and re-leveled the concept with strong numbers and substantial allied clinical data. Great appreciation must be expressed to the labs in Russia who conduct such dutiful and comprehensive surveillance. The world benefits from data transparency.
A proper dataset was derived by examining the 20 Russian cases from the month of November that provided the required HA and NA sections for cross-segment analysis. The data is reasonably varied on several axes. The sequences were sampled in a range from November 2 to November 30, span 12 distinct geographies and include cases from locales with previous deposits (useful in comparative delta studies). 15 of the 20 sequences demonstrate cross-linking. With Russia calculating to 75% cross-linking, a new threshold is established.
Cross-Linkage Percentage
- 23% Germany . . . . . 2010-04-15
- 53% Netherlands . . . 2010-06-29
- 75% Russia . . . . . 2010-06-01
An increase from 0.5% to 75% draws the eye for further analysis and the sequences tell the truth. 14 of the cross-linked sequences from November in this Russian deposit are confirmed fatalities. 93% of the humans carrying these two "silent" genetic markers died of pandemic influenza. Only 9 of those cases showed a change at amino acid position 225, suggesting that revision at position 225 is not required for expiration, though the combination with cross-linkage suggests increased virulence. The synonymous pairing of HA 413K and NA 407V represents a strong correlation at this point to fatal human cases of pH1N1.
Bear in mind that the United States may lead the world in cross-linkages cases. The count of examined cases is clearly equal to Russia, but more importantly, the partial sequences on file show a strong pattern that cannot be validated or denied due to baffling truncations of data. Western Europe is at significant risk as Spain is currently inundated with these markers and may have been an early donation source to the Ukraine. Other European countries on the wild bird migration FlightPath (Italy and Greece) also pattern the truncations of data that disallow proper validation.
The greater portion of revisions found on these fatal Russian cross-linked sequences share homology with known zoonotic Influenza reservoirs. Most of the cross-linked sequences are hyper-morphic. 95 polymorphisms among only 15 November sequences solve for an average 6.33 changes per cross-linked HA. Three of the HA sequences have 8 revisions and only one has less than 5 polymorphisms. Ulyanovsk_KLA_2009_11_13_xL_f with only 3 changes (all “silent”) was, nonetheless, fatal to the person infected.
Phylogenentic analysis demonstrates significant genetic diversity within this set of cross-linked sequences. The unrooted tree of all 19 xL cases in this deposit (Figure A including pre- and post-November) provides leafing evidence of wide variation. This wide variation suggests an ease of syn413K recombination across multiple disparate pathways or, in a logic reversal, that HA syn413K / NA syn407V may act as a catalyst for increased and varied genetic acquisitions.
Figure A: Tree of Russian Cross-Linked Sequences from 2010-06-01 Deposit
The PF11 background is primed for zoonotic inclusions due to the present wild type homology with recognised avian sources at 138A, 194L, 226Q and 228G. Perhaps the syn413K completes some odd biological circuit with these recognised Avian markers in PF11, allowing a surge of acquisitions. The ongoing presence of the Avian 225G throughout the world signals five of the six Avian differentiation polymorphic locations are habitually found in this human pandemic reservoir. 190E, the sixth and final Avian revision area from the 2000-06 joint study on early pandemic RBD alterations has been predicted for PF11, but not yet publicly documented due to data sparsity and lab procedures that bias sequence output.
The following two annotated phylogenetic trees suggest that the xL background is magnetized for changes at 225. For simplicity of illustration, the first annotated tree (Figure B) reviews a set of three triples. Each triple set has one xL sequence with wild type 225 and two Russian sequences related by homology, one each with 225G and 225N. Revision at 225 occurs with great facility on this background.
Figure B: Tree of 3 Selected xL sequences & related Russian cases
The second annotated tree (Figure C) expands an early branch of Figure B, demonstrating the diversity and penetration of the syn177L, 324I, syn413K, syn542S grouping. The manifestation of three additional 225G strains (Ivanovo_AIV, Ivanovo_BOV, MoscowOb_OAM) at this early branch does not appear random, but is indicative that parallel patterns of accumulation are occurring across backgrounds with the silent HA 413K polymorphism.
Figure C: Tree of 3 Selected xL sequences & related Russian cases, expanded
Furthermore, these polymorphisms that have accumulated onto the sequences in Russia align with non-human Influenza reservoirs such as wild birds, domestic food poultry (chickens and turkeys), domestic pets (cats and dogs) and in equines used for racing (horse) and agriculture (donkey).
H5N1, H3N8, H7N7 and H9N2 feature prominently.
The sequence details provide case location, date of sample, indication of cross-linkage (_xL), indication of fatality (_f) and a color coding marking the samples bearing HA 225G. None of these November xL sequences carry the more virulent HA 225N, though 3 homology-related fatal 225N sequences are found in the larger Russia 2010-06-01 deposit. Polymorphisms followed by brackets demonstrate the listing of non-human Influenza serotypes that carry instances of the particular change.
Sometimes density is required for understanding. The truth is in the sequences.
Ivanovo_AMV_2009_11_xL_f (
. . . . syn177L [H3N8, H6, H7N7],
. . . . 225G mix,
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Kaluga_INV_2009_11_xL _f (
. . . . 225G mix,
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . 491E [H11],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
MoscowOb_DEI_2009_11_xL_f (
. . . . syn177L [H3N8, H6, H7N7],
. . . . 225G,
. . . . syn310V [H3N8, H5N1 (E/A/H), H6, H7N7, H11],
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
MoscowOb_OAM_2009_11_02_xL_f (
. . . . syn177L [H3N8, H6, H7N7],
. . . . syn205G [H6, H7N7],
. . . . 225G,
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Lipetsk_BVV_2009_11_10_xL_f (
. . . . syn177L [H3N8, H6, H7N7],
. . . . 225G mix,
. . . . syn238E [H2, H4],
. . . . syn240G [H3N8, H6, H9N2, H11],
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Ulyanovsk_KLA_2009_11_13_xL_f (
. . . . syn372Q [H2, H3N8, H4, H5, H6, H7N3, H7N7, H9N2, H11],
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Stavropol_BLV_2009_11_18_xL (
. . . . syn6L [H3N8],
. . . . 19I [H3N8],
. . . . syn177L [H3N8, H6, H7N7],
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Moscow_CHSN_2009_11_23_xL_f (
. . . . syn177L [H3N8, H6, H7N7],
. . . . 225G,
. . . . 324I,
. . . . syn376D [H2, H3N8, H4, H5, H6, H7N3, H7N7, H9N2, H11],
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn484N [H3N8, H4, H5N1 (E/A/H), H6, H7N7, H9N2, H11]),
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
MoscowOb_KMA_2009_11_23_xL_f (
. . . . 38G [H3N8],
. . . . 225G mix,
. . . . 264T,
. . . . 324I,
. . . . 491E [H11],
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Astrakhan_CHRM_2009_11_24_xL_f (
. . . . syn71E [H6N1],
. . . . syn109S [H2, H3N8, H9N2, H11],
. . . . syn177L [H3N8, H6, H7N7],
. . . . syn214K [H9N2],
. . . . 324I,
. . . . syn355H [H2, H5N1, H6N1],
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Ivanovo_RNA_2009_11_24_xL_f (
. . . . 0I,
. . . . syn168Y [H9N2],
. . . . 225G/225N/225D wt,
. . . . 269V [H9N2, H11],
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn426A [H2, H4, H5, H6, H7N7, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
MoscowOb_ZNF_2009_11_24_xL_f (
. . . . syn71E [H6N1],
. . . . syn109S [H2, H3N8, H9N2, H11],
. . . . syn177L [H3N8, H6, H7N7],
. . . . 324I,
. . . . syn331G [H3N8, H4, H6, H7N3, H7N7, H11]
. . . . syn355H [H2, H5N1, H6N1],
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Arkhangelsk_GNY_2009_11_25_xL_f (
. . . . syn134G [H2, H3N8, H4, H5N1 (E/A/H), H6, H9N2, H11],
. . . . syn177L [H3N8, H6, H7N7],
. . . . syn238E [H2, H4],
. . . . syn240G [H3N8, H6, H9N2, H11],
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . 437N,
. . . . syn484N [H3N8, H4, H5N1 (E/A/H), H6, H7N7, H9N2, H11])
HA and NA
Ivanovo_KOE_2009_11_25_xL_f (
. . . . syn177L [H3N8, H6, H7N7],
. . . . syn310V [H3N8, H5N1 (E/A/H), H6, H7N7, H11],
. . . . 324I,
. . . . syn359E [H5, H7N7, H11],
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
Tambov_LLA_2009_11_30_xL_f (
. . . . syn177L [H3N8, H6, H7N7],
. . . . 225G/225N/225D wt,
. . . . syn310V [H3N8, H5N1 (E/A/H), H6, H7N7, H11],
. . . . 324I,
. . . . syn413K [H2, H5N1, H9N2],
. . . . syn542S [H2, H5N1, H9N2])
HA and NA
2010-03-17
Cross-Linked Background Supporting Fatal 225G Cases Penetrates 3 New Countries: Poland, Denmark and Greece
Cross-Linked Silent HA and NA Polymorphisms Correlated with Fatal 225G Cases in the Ukraine and Russia
AthensINS85 demonstrates a silent revision at amino acid 233 on the HA. The Duke North Carolina Tamiflu-Resistant cluster of 225G cases carries identifying revisions at HA amino acid position 233. Though the Duke changes at 233 are not equal to the polymorphism from Greece, indications of movement at 233 in the December Greek sequence subsequent to the North Carolina cases may signal the need for a more detailed study. Several North Carolina sequences from humans and swine fall on the cross-linked background.
Areas covered include Texas (3), the Northeastern United States (5), Kentucky, Indiana, North Carolina (5), China (2), Singapore, Australia (2), the Ukraine (23), Moldova (5), Russia (18), Iraq (3), Denmark(3), Norway (2), Sweden (2), Poland, Greece and extensive penetration in Spain (17 sequences).
This particular cross linked background pattern may precurse 225G and mixtures of 225D / 225G. The Orenburg2974 sequence from Russia carries 225N on this background. Receptor Binding Site (RBS) changes at 225 are associated with fatality, 225G and 225N at a rate higher than 225E.
If LvivN6 is officially confirmed as a vaccine escape event, these cross-segment pairs may be surveilled as potential future effectors of vaccine efficacy failure.
Previous Study on this Topic:
- HA:syn413K encoded from A1281G, AAa->AAg
- NA:syn407V encoded from T1221C, GTt->GTc
- Iraq8529E3 with HA 131L, 160L, 194I, 298V and syn419L (Kentucky19 and 225G Utah42)
- Iraq8529M1 with HA 131L, 160L, 298V and syn419L (Kentucky19 and 225G Utah42)
- Iraq8531 with HA 130E, 131L, 298V and syn419L (Kentucky19 and 225G Utah42)
- Australia Victoria2129 with potential H5N2 inclusions and NA 454S
- Australia Victoria2130 with NA 454S
- Ukraine Kyiv377 with mixture of 225D, 225G, 225N, 225S, 225T and 225A
- Ukraine Lviv673
- Ukraine Lviv682
- Ukraine Cherkasy332
- Ukraine Cherkasy333
- Ukraine Cherkasy346
- Ukraine Chernihiv855L with mixture of wt 225D / 225G and additional 1918 Markers (syn238E & 324I), Fatal outcome
- Ukraine Chernihiv856 with mixture of wt 225D / 225G , Fatal outcome
- Ukraine Chernihiv857 with mixture of wt 225D / 225G and additional 1918 Markers (186P, syn238E, 324I & G796A), Fatal outcome
- Ukraine Chernihiv858, Fatal outcome
- Ukraine Dnipropetrovsk260
- Ukraine Dnipropetrovsk267
- Ukraine Dnipropetrovsk268
- Ukraine Dnipropetrovsk272
- Ukraine Dnipropetrovsk273 with mixture of wt 225D and 225G
- Ukraine Dnipropetrovsk274
- Ukraine Dnipropetrovsk1124
- Ukraine Dnipropetrovsk1171
- Ukraine LvivN2 with 225G
- Ukraine LvivN6 with 225G
- Ukraine TernopilN10 with 225G
- Ukraine TernopilN11 with 225G
- Ukraine Volin226 with 225G
- MoldovaG120
- MoldovaG140
- MoldovaG181
- MoldovaG182
- MoldovaG191
- HA and NA Norway2924 with mixture of wt 225D and 225G
- HA and NA Norway3364-2
- HA and NA Denmark AarhusINS82 with syn177L and 324I *
- HA and NA Denmark CopenhagenINS95 with 69K, syn157K and 176I *
- HA and NA Denmark CopenhagenINS98 *
- HA and NA Poland WarsawINS100 with 324I and 377K *
- HA and NA Greece AthensINS85 with syn57C, syn233Y, 324I and 377K *
- HA and NA CatNS7362 TamiFlu Resistant
- HA and NA CatS1096
- HA and NA CatS1162
- HA and NA CatS1179
- HA and NA CatS1181
- HA and NA CatS1267
- HA and NA CatS1268
- HA and NA CatS1402
- HA and NA CatS1501
- HA and NA CatS1687
- HA and NA CatS1748
- HA and NA CatS1751
- HA and NA CatS1761
- HA and NA CatS1827
- HA and NA CatS1935
- HA and NA CatS2120 with multiple swine markers
- HA and NA CatS2151 with swine markers and 165N (TamiFlu Resistant CatNS7632 and Russian 225G Salekhard01)
- HA and NA Guangdong02
- HA and NA Guangdong05
- HA and NA SingaporeON1156
- HA and NA Stockholm31
- Sweden Gothenburg2 with 146G, 324I (1918) and markers found extensively in Moldova and Russia
- HA and NA Russia4 with syn238E and 324I (1918)
- HA and NA Russia12 with 324I (1918)
- HA and NA Russia14
- HA and NA Russia19 with 324I (1918)
- HA and NA Russia74
- HA and NA Russia149
- HA and NA Russia165
- HA and NA Russia171 with 165N
- HA and NA Russia178
- HA and NA Russia180 with 165N, syn239P and 264G
- HA and NA Russia190
- HA and NA Russia191
- HA and NA Kurgan01 with HA 214E (MoldovaG168, G176, G188) and NA mixture at 407 (Fatal 225G Abakan02)
- HA and NA Omsk02
- HA and NA Tver2969 with 225G, Fatal outcome
- HA and NA Salekhard01 with 165N and 225G, presumptive Fatal outcome
- HA and NA Orenburg2974 with 225N, potential Fatal outcome
- HA and NA Perm01 with 131P, 225G and 324I, presumptive Fatal outcome
- HA and NA NY3702
- HA and NA NY3715
- HA and NA NY3828
- United States NewYork96
- HA and NA RhodeIsland08
- HA and NA Texas42102708
- HA and NA Texas45072128
- HA and NA Texas45122886
- United States Kentucky19 from an 18 year old subject with HA 298V
- United States Indiana20 from a 10M subject with 5 Avian H5N1 markers
- US Private Sequence TamiFlu Resistant
- United States NorthCarolina37 from a 24F subject with HA 298V
- United States NorthCarolina44 from a 50M subject with 6 Avian H5N1 markers
- United States NorthCarolina46_C2 from a 39F subject with HA 298V
- United States NorthCarolina46_C2C1 from a 39F subject with HA 298V
- HA and NA swine/NC/34752 with 298V
AthensINS85 demonstrates a silent revision at amino acid 233 on the HA. The Duke North Carolina Tamiflu-Resistant cluster of 225G cases carries identifying revisions at HA amino acid position 233. Though the Duke changes at 233 are not equal to the polymorphism from Greece, indications of movement at 233 in the December Greek sequence subsequent to the North Carolina cases may signal the need for a more detailed study. Several North Carolina sequences from humans and swine fall on the cross-linked background.
Areas covered include Texas (3), the Northeastern United States (5), Kentucky, Indiana, North Carolina (5), China (2), Singapore, Australia (2), the Ukraine (23), Moldova (5), Russia (18), Iraq (3), Denmark(3), Norway (2), Sweden (2), Poland, Greece and extensive penetration in Spain (17 sequences).
This particular cross linked background pattern may precurse 225G and mixtures of 225D / 225G. The Orenburg2974 sequence from Russia carries 225N on this background. Receptor Binding Site (RBS) changes at 225 are associated with fatality, 225G and 225N at a rate higher than 225E.
If LvivN6 is officially confirmed as a vaccine escape event, these cross-segment pairs may be surveilled as potential future effectors of vaccine efficacy failure.
Previous Study on this Topic:
- 2010-01-28 Ukraine - 100% of New Sequences with Required HA and NA on Cross-Linked Background; 225G on 6 of 11; 1918 Markers Coalesce
- 2010-01-19 Fatal Ukraine Cross Segment Linkage Extends in the US, Iraq and Australia (HA syn413K and NA syn407V)
- 2010-01-01 HA syn413K and NA syn407V Cross Segment Linkage Increases Range and Penetration
- 2009-12-04 Spain Introduces 2 November Sequences with Cross-Segment Pairing from Fatal Cases in the Ukraine
- 2009-11-28 Ukraine and Spain Cross-Linked HA and NA Silent Changes Circle the Globe
- 2009-11-26 The Ukraine, Norway and Spain Share Paired HA and NA Changes
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