Showing posts with label Sweden. Show all posts
Showing posts with label Sweden. Show all posts

2011-09-20

H5N1 Avian Markers, Side by Side, in 2011 Human pH1N1 Stockholm, Sweden Case

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
2011-09-20

On 2011-07-29, the UK National Institute for Medical Research published 29 pH1N1 sequences at GISAID.  These sequences were sampled from patients in Scandinavia, Eastern Europe, the Balkans and Hong Kong from January to May 2011 covering the second half of the Northern Hemisphere 2010-2011 season.  The Swedish Institute for Infectious Disease Control originated 10 of the samples in this Mill Hill deposit including a highly zoonotic and potential H5N1 recombinant, Stockholm13_2011_03_28, with no specified gender, age or outcome.

Two contiguous H5N1 Avian markers, HA 415E and 416N, each novel to the human H1N1 pandemic, appear in this human case.  The HA 416N is reported as a mixed peak trace, an output that is commonly interpreted as suggestive of multiple infecting strains.  The single H5N1 potential donor HA segment on file is also unusual in that this Egyptian domestic poultry sequence carries numerous homologies to polymorphisms found on human pH1N1 Clade 1 (189T) and Clade 2 (188T) sequences.  Several of those H5N1 to pH1N1 homologies are quite rare to H5N1, but are strongly emergent in pH1N1.

Stockholm13_2011_03_28 was sampled near the end of the traditional Northern Hemisphere influenza season and, as such, represents one probable foundation for ongoing Clade 2 transmission into the upcoming influenza season (2011-2012).  As has been regularly discussed, Clade 2 (188T) is the most prevalent numerically of the 5 major pH1N1 divisions as reported in the public and private genetic databases.  Being roughly par for the course, this Swedish sequence is hypermorphic, carrying 14 polymorphisms (9 Amino and 5 Silent).

Particular to the matter at hand, Clade 2 sequences have demonstrated a measurable propensity for accepting polymorphisms into pH1N1 and projecting those changes across pH1N1 (“Clade Jumping” / Clade Transfer).  The method and means continue under investigation, whether due to the influence of Avian H1N1 common ancestry from the primary donors into the major human pH1N1 clades or due to some form of recombination / attractant magnetism occurring between and among the human pH1N1 clades.

GeneWurx has tracked development of the H1N1 pandemic from the publicly accepted Contact Zero in early 2009 (and potential prequels) up to the present emergent strains.  As with prior H5N1 investigations, random variation remains far from the field of explanatory options in most cases.  Malleability by random mallet has not been shown as an important means of genetic variation in this H1N1 human pandemic.

The back-to-back polymorphisms transferring HA 415E and 416N onto the human pH1N1 Stockholm13_2011_03_28 sequence are noted in the H5N1 database.  That single H5N1 sequence is a human-adapted, avian case from Egypt.  This dual signal transfer demonstrates one very concrete case of cross-species, cross-serotype genetic transfer from an animal to a human serotype. 

H5N1 contiguous homology to the dominant clade in the dominant circulating human serotype (pH1N1) instructs the medical fraternity to the weight of emergent zoonoses and suggests that at least one avian flightpath may be worthy of investigation.

. . . . SwedenStockholm13_2011_03_28 (
. . . . . . . . PHz = 87%
. . . . . . . . PHzAv = 87%
. . . . . . . . GISAID HA EPI326240
. . . . . . . . 14 Polymorphisms (9 Amino and 5 Silent)
. . . . . . . . syn41N (AAt) [H5N1 Human Emergent with TamiFlu Resistance],
. . . . . . . . . . . . . . . . .  [H5N1 Egypt Human 2007],
. . . . . . . . . . . . . . . . .  [H5N1 Avian with 166I],
. . . . . . . . 50I [WSN_1933, WSZ_1933],
. . . . . . . . . .  [1918],
. . . . . . . . syn154L (tTA) [H3N2 Avian with 158E],
. . . . . . . . . . . . . . . . . . [H3N2 Canine, Feline wt]
. . . . . . . . . . . . . . . . . . [H3N2 Human wt (tTg)],
. . . . . . . . . . . . . . . . . . [H3N8 Avian (tTg)],
. . . . . . . . . . . . . . . . . . [H9N2 Avian with 404G],
. . . . . . . . . . . . . . . . . . [H9N2 Avian (tTg)],
. . . . . . . . . . . . . . . . . . [H9N2 Human with syn40H (tTg)],
. . . . . . . . 158E mix wt [H3N8, H5N1],
. . . . . . . . . . . . . . . . . [H3N2 Avian],
. . . . . . . . . . . . . . . . . . . . with 165N, 190E, 225G, 230I, 238K
. . . . . . . . . . . . . . . . . . . . . . . 253A, 275I, syn346G],
. . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . with #1T, 8V, syn31H, syn40H, syn42G,
. . . . . . . . . . . . . . . . . . . . . . . 72L, syn80S, syn82I, 87N, syn118E,
. . . . . . . . . . . . . . . . . . . . . . . 144E, 189T, 193R, 237I,
. . . . . . . . . . . . . . . . . . . . . . . syn287G, syn346G, 523A],
. . . . . . . . . . . . . . . . . [sw1930],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . . . . . [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],
. . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . with 186P, 189T,
. . . . . . . . . . . . . . . . . . . and extensive pH1N1υ polymorphisms],
. . . . . . . . 259T [H9N2 Avian and Human (att)
. . . . . . . . . . . . . . . . with syn40H],
. . . . . . . . syn338G (GGc) [H3N2 Avian, Canine, Feline],
. . . . . . . . . . . . . . . . . . [H3N8, H4, H5N1 Avian 2010, H6, sw],
. . . . . . . . . . . . . . . . . . [H1N1 Avian Farm with syn346G],
. . . . . . . . 377K [H9N2],
. . . . . . . . syn388K (AAa) [Wisconsin08_30F_2010_08_10
. . . . . . . . . . . . . . . . . . . . . with 39R, 137T, 186P,
. . . . . . . . . . . . . . . . . . . . . . . . . 225N, syn346G, syn413K, 444K,
. . . . . . . . . . . . . . . . . . Utah20_C2_2_2009_07_25_VxX
. . . . . . . . . . . . . . . . . . . . . with #12E, 0I, 159D, 227G, 296H, 470I],
. . . . . . . . . . . . . . . . . . [H5N1 Avian, Equine, Human wt],
. . . . . . . . . . . . . . . . . . [H9N2 Avian and Human
. . . . . . . . . . . . . . . . . . . . . . with 39E, syn40H, syn42G, 296H],
. . . . . . . . . . . . . . . . . . [swIowa44837_1_2009_11_08_xL
. . . . . . . . . . . . . . . . . . . . . . with syn41N, 50I, 196H,
. . . . . . . . . . . . . . . . . . . . . . . . . 225N, 230I, 238D,
. . . . . . . . . . . . . . . . . . . . . . . . . syn346G, syn413K],
. . . . . . . . 415E [H5N1 Egypt wt],
. . . . . . . . 416N mix [H5N1 Avian Egypt
. . . . . . . . . . . . . . . . . . . with 100N, 196H, 415E],
. . . . . . . . 416Y mix,
. . . . . . . . 454N [H7N3, H7N7, H9N2],
. . . . . . . . syn527L (TTa) [BeijingHZ01_2011_01_14
. . . . . . . . . . . . . . . . . . . . . . . . with 188T, 242N],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt wt (cTa)]





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

2011-06-09

Sweden Signals Rapid Zoonosis from Avian H1N1 on Emergent Tertiary SubClade

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 Updated
2011-06-09

On 2011-06-07, the Swedish Institute for Infectious Disease Control published one pH1N1 sequence at GISAID sampled in February 2011.  Six of the HA revisions are commonly found on sequences from the historical Avian H1N1 reservoir with the HA syn221P being conserved in the Avian species across both major circulating human Influenza A serotypes, H1N1 and H3N2.  This heavily avian background appears to be transmitting well in humans with cases in Switzerland, France and Estonia that continue the avian influence pattern.

A very practical implication is that many of these Avian sequences bearing the noted individual polymorphisms from this Swedish 208K_219V pH1N1 SubClade 5 sequence also carry polymorphisms that have been demonstrated on another pH1N1 subclade, the HA 189T-bearing Upsilon with a 5.8% Case Fatality Rate.  When several of the circulating human subclades are filling with Avian polymorphisms that are multiply co-located on single Avian reservoir sequences, expectations of zoonoses onto pH1N1 are heightened while the currently documented polymorphism-jumping between these very attractant pH1N1 dominant subclades is ensured.

Viable permutations rise.

“Everything that rises must converge.”

. . . . SwedenLinkoping8_20F_2011_02_17 (
. . . . . . . . GISAID HA EPI319566
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn102E (GAa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt) [H3N2 Avian
. . . . . . . . . . . . . . . . . . . . . . with 157S, 159S, syn287G],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 252L,
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))

. . . . SwedenLinkoping8_20F _2011_02_17 (
. . . . . . . . GISAID NA EPI319567
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . syn60T (ACc),
. . . . . . . . 81A,
. . . . . . . . syn138A (GCt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

Supporting Sequences

. . . . Estonia55306_3F_2011_03_03 (
. . . . . . . . GISAID HA EPI319465
. . . . . . . . 12 Polymorphisms (5 Amino and 7 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . syn254P (CCa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))

. . . . Estonia55306_3F_2011_03_03 (
. . . . . . . . GISAID NA EPI319466
. . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
. . . . . . . . syn119E (GAg),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . Estonia54375_51F_2011_02_11 (
. . . . . . . . GISAID HA EPI319459
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))

. . . . Estonia54375_51F_2011_02_11 (
. . . . . . . . GISAID NA EPI319460
. . . . . . . . 9 Polymorphisms (3 Amino and 6 Silent)
. . . . . . . . syn60T (ACc),
. . . . . . . . syn67V (GTc),
. . . . . . . . 81A,
. . . . . . . . syn138A (GCt),
. . . . . . . . syn221N (AAt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . Estonia54132_18F_2011_02_08 (
. . . . . . . . GISAID HA EPI319457
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))

. . . . Estonia54132_18F_2011_02_08 (
. . . . . . . . GISAID NA EPI319458
. . . . . . . . 8 Polymorphisms (3 Amino and 5 Silent)
. . . . . . . . syn24L (TTg),
. . . . . . . . 81A,
. . . . . . . . syn138A (GCt),
. . . . . . . . syn216I (ATt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . SwitzerlandGeneva4201955_xF_2011_01_06 (
. . . . . . . . GISAID HA EPI309651
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . 157N mix wt,
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))

. . . . SwitzerlandGeneva4201955_xF_2011_01_06 (
. . . . . . . . GISAID NA EPI309652
. . . . . . . . 9 Polymorphisms (3 Amino and 6 Silent)
. . . . . . . . 81A,
. . . . . . . . syn138A (GCt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn271A (GCt),
. . . . . . . . syn298G (GGa),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn449N (AAt))

. . . . FranceLyon3_58x_2010_12_31 (
. . . . . . . . GISAID HA EPI319497
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))

. . . . FranceLyon3_58x_2010_12_31 (
. . . . . . . . GISAID NA EPI319498
. . . . . . . . 9 Polymorphisms (3 Amino and 6 Silent)
. . . . . . . . syn60T (ACc),
. . . . . . . . 81A,
. . . . . . . . syn124C (TGt),
. . . . . . . . syn138A (GCt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn382G (GGa))

. . . . Iowa04_2009_04_24 (
. . . . . . . . GISAID HA EPI179262
. . . . . . . . 3 Polymorphisms (1 Amino and 2 Silent)
. . . . . . . . 206S,
. . . . . . . . syn221P (CCt),
. . . . . . . . syn498L (TTg))

. . . . Iowa04_2009_04_24 (
. . . . . . . . GISAID NA EPI186289
. . . . . . . . 2 Polymorphisms (0 Amino and 2 Silent)
. . . . . . . . syn306F (TTt),
. . . . . . . . syn307N (AAt))










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

2011-06-03

Sweden Demonstrates Extensive Winter 2011 Diversity with 5 pH1N1 SubClades Represented on 11 Deposited Sequences

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 Updated
2011-06-03

Across 2011-05-30 and 05-31, the Swedish Institute for Infectious Disease Control published 11 pH1N1 sequences at GISAID sampled in a time period spanning January to April 2011 with the majority in February (6).  The two deposits merit discussion due to the wide variety of backgrounds demonstrated across such a small population of sequences. 

A minimum of 5 Pandemic H1N1 subclades are represented in these 11 Swedish sequences.  More than one represented subclade carries revisions that have been associated with laboratory-determined “Low Reactor” status or with illness in previously vaccinated subjects.  None of the 11 Swedish sequences fall onto the Pandemic H1N1 Upsilon subclade (pH1N1υ), but several, including one Swedish fatality of a 10 year old male, have crossover polymorphisms previously described in the pH1N1υ superset.

130 polymorphisms (67 amino and 63 silent) are found on these 11 HA segments with 69 distinct HA changes.  The 11 NA segments demonstrate 77 polymorphisms (41 amino and 36 silent) with 38 distinct NA changes.  207 total polymorphisms on 11 Swedish sequences (HA + NA) averages to 18.8 changes per sequence.  A minimum of 5 subclades with 18 changes per sequence, many at known epitopes (antigenic sites), factors as a significantly difficult target to match with a “single-strain per serotype” vaccine strategy. 

Measurable potential for Vaccine Escape increases with circulating diversity as found on these moving targets in Scandinavia and with the clinical and experimental indications of vaccine failure, e.g. HA 128D, HA 158E, et al.

Four of the 11 HA sequences demonstrate 188T of the first pH1N1 emergent nucleotide coding and 2 of those Swedish 188T sequences additionally carry HA 158E in a mixture with wild type.  Another 4 of the 11 HA sequences demonstrate 186P with one additionally carrying HA 158E in a mixture with wild type on a background with avian influenza polymorphisms.  A concentration of 3 HA 158E revisions in 11 samples mimics the high levels found previously in other Asian and European geographies.  The penetration of HA revisions between aa156 and aa159 in Scandinavia is crossing backgrounds and appears to be accelerating.

The fatal case, SwedenMalmoe5_10M_2011_04_21_f, carries 12 HA changes including revision at aa144 (positional to pH1N1υ 144E & 144T) and equality to the pH1N1υ superset at syn287G & 377K.  Eight NA changes on the fatal sequence bring the polymorphic total to 20.  That total suggests that aggressive viral revision is correlated to fatal and severe cases.  These recent high incidences of polymorphism jumping between human subclades appear to follow the dictates of co-location on zoonotic avian sequences.

HA

. . . . SwedenMalmoe5_10M_2011_04_21_f (
. . . . . . . . GISAID EPI318269
. . . . . . . . 12 Polymorphisms (6 Amino and 6 Silent)
. . . . . . . . 137T,
. . . . . . . . 144S,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg),
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V,
. . . . . . . . syn363G (GGg),
. . . . . . . . 377K,
. . . . . . . . syn474C (TGt),
. . . . . . . . 482I)

. . . . SwedenUppsala6_67F_2011_03_11 (
. . . . . . . . GISAID EPI318263
. . . . . . . . 13 Polymorphisms (6 Amino and 7 Silent)
. . . . . . . . 137T,
. . . . . . . . 144S,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg),
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V,
. . . . . . . . syn363G (GGg),
. . . . . . . . 377K,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn480E (GAg),
. . . . . . . . 482I)

. . . . SwedenLinkoping7_19F_2011_03_09 (
. . . . . . . . GISAID EPI318260
. . . . . . . . 15 Polymorphisms (7 Amino and 8 Silent)
. . . . . . . . syn42G (GGa),
. . . . . . . . syn47L (CTg),
. . . . . . . . syn58C (TGc),
. . . . . . . . syn82I (ATc),
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N,
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc),
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))

. . . . SwedenStockholm14_32M_2011_02_15 (
. . . . . . . . GISAID EPI318257
. . . . . . . . 18 Polymorphisms (9 Amino and 9 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn33V (GTc),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn99I (ATt),
. . . . . . . . 132S,
. . . . . . . . syn139C (TGc),
. . . . . . . . 145R,
. . . . . . . . 146G,
. . . . . . . . 158E mix wt,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn456L (TTg),
. . . . . . . . syn465N (AAt),
. . . . . . . . 496S,
. . . . . . . . syn538F (TTt))

. . . . SwedenStockholm12_2011_02_13 (
. . . . . . . . GISAID EPI318241
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn431L (tTA),
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))

. . . . SwedenStockholm13_2011_02_09_sH1N1 (
. . . . . . . . GISAID EPI318247
. . . . . . . . 12 Polymorphisms (5 Amino and 7 Silent)
. . . . . . . . syn41N (AAt),
. . . . . . . . 50I,
. . . . . . . . syn154L (tTA) [swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . . . . . . . . with syn69E, 100N, syn154L (CTg),
. . . . . . . . . . . . . . . . . . . . . . . . . 189T, syn215P, 298V,
. . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . syn448L (cTA), syn474C, 482I],
. . . . . . . . 158E mix wt,
. . . . . . . . 188T,
. . . . . . . . 259T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn388K (AAa),
. . . . . . . . 415E mix wt,
. . . . . . . . 454N,
. . . . . . . . syn527L (TTa))

. . . . SwedenStockholm10_2011_02_06 (
. . . . . . . . GISAID EPI318238
. . . . . . . . 11 Polymorphisms (7 Amino and 4 Silent)
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa) [swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . . . . . . . . with syn69E, 100N, syn154L (CTg),
. . . . . . . . . . . . . . . . . . . . . . . . . 189T, syn215P, 298V,
. . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . syn448L (cTA), syn474C, 482I],
. . . . . . . . 100N,
. . . . . . . . 166I [Novel to pH1N1 188T SubClades],
. . . . . . . . 188T,
. . . . . . . . syn215P (CCa) [Vladivistok7_2010_12_03 with 188T],
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 414I [swThailandCU_RA75_2010_01 with 188T],
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))

. . . . SwedenStockholm11_2011_02_05 (
. . . . . . . . GISAID EPI318235
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn448L (TTg) [swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . . . . . . . . with syn69E, 100N, syn154L (CTg),
. . . . . . . . . . . . . . . . . . . . . . . . . 189T, syn215P, 298V,
. . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . syn448L (cTA), syn474C, 482I],
. . . . . . . . 454N)

. . . . SwedenMalmoe4_2011_02_13 (
. . . . . . . . GISAID EPI318254
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . syn60I (ATc),
. . . . . . . . 128D,
. . . . . . . . syn218A (GCg),
. . . . . . . . syn273T (ACg),
. . . . . . . . 286E,
. . . . . . . . 377K,
. . . . . . . . syn469E (GAg))

. . . . SwedenUmea1_35x_2011_01_28 (
. . . . . . . . GISAID EPI318266
. . . . . . . . 14 Polymorphisms (7 Amino and 7 Silent)
. . . . . . . . syn98F (TTt),
. . . . . . . . 137T,
. . . . . . . . 144S,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg),
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V,
. . . . . . . . syn363G (GGg),
. . . . . . . . 377K,
. . . . . . . . 397D mix wt,
. . . . . . . . syn474C (TGt),
. . . . . . . . 482I)

. . . . SwedenGothenburg1_2011_01_16 (
. . . . . . . . GISAID EPI318244
. . . . . . . . 14 Polymorphisms (6 Amino and 8 Silent)
. . . . . . . . 137T,
. . . . . . . . 144S,
. . . . . . . . 158E mix wt,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg),
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V [swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . . . . . . . . with syn69E, 100N, syn154L (CTg),
. . . . . . . . . . . . . . . . . . . . . . . . . 189T, syn215P, 298V,
. . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . syn448L (cTA), syn474C, 482I],
. . . . . . . . syn346G (GGa),
. . . . . . . . syn363G (GGg),
. . . . . . . . 377K,
. . . . . . . . syn474C (TGt),
. . . . . . . . 482I)

NA

. . . . SwedenMalmoe5_10M_2011_04_21_f (
. . . . . . . . GISAID EPI318270
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . 46T,
. . . . . . . . syn187G (GGt),
. . . . . . . . 313R,
. . . . . . . . syn336G (GGc),
. . . . . . . . syn370G (GGc),
. . . . . . . . 394I,
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)

. . . . SwedenUppsala6_67F_2011_03_11 (
. . . . . . . . GISAID EPI318264
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 46T,
. . . . . . . . syn47E (GAg),
. . . . . . . . syn187G (GGt),
. . . . . . . . 313R,
. . . . . . . . 394I,
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)

. . . . SwedenLinkoping7_19F_2011_03_09 (
. . . . . . . . GISAID EPI318261
. . . . . . . . 6 Polymorphisms (1 Amino and 5 Silent)
. . . . . . . . syn89S (TCt),
. . . . . . . . syn126P (CCt),
. . . . . . . . syn229S (TCc),
. . . . . . . . syn236G (GGc),
. . . . . . . . syn241V (GTg),
. . . . . . . . 299A)

. . . . SwedenStockholm14_32M_2011_02_15 (
. . . . . . . . GISAID EPI318258
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 20T,
. . . . . . . . 44S,
. . . . . . . . 119K mix wt,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn378N (AAt))

. . . . SwedenMalmoe4_2011_02_13 (
. . . . . . . . GISAID EPI318255
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 240I,
. . . . . . . . 264I,
. . . . . . . . syn339S (TCa),
. . . . . . . . syn383T (ACt),
. . . . . . . . 397K,
. . . . . . . . 442I)

. . . . SwedenStockholm12_21F_2011_02_13 (
. . . . . . . . GISAID EPI318242
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 83M,
. . . . . . . . 173K,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . SwedenStockholm13_2011_02_09 (
. . . . . . . . GISAID EPI318248
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . 20T,
. . . . . . . . 40I,
. . . . . . . . 46T,
. . . . . . . . syn157T (ACt),
. . . . . . . . syn229S (TCc),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . SwedenStockholm10_31F_2011_02_06 (
. . . . . . . . GISAID EPI318239
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . SwedenStockholm11_38F_2011_02_05 (
. . . . . . . . GISAID EPI318236
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . syn162P (CCc),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn398E (GAa),
. . . . . . . . syn416D (GAc))

. . . . SwedenUmea1_35x_2011_01_28 (
. . . . . . . . GISAID EPI318267
. . . . . . . . 7 Polymorphisms (5 Amino and 2 Silent)
. . . . . . . . 46T,
. . . . . . . . syn187G (GGt),
. . . . . . . . 273T,
. . . . . . . . 313R,
. . . . . . . . 394I,
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)

. . . . SwedenGothenburg1_22M_2011_01_16 (
. . . . . . . . GISAID EPI318245
. . . . . . . . 7 Polymorphisms (5 Amino and 2 Silent)
. . . . . . . . 46T,
. . . . . . . . 79P,
. . . . . . . . syn187G (GGt),
. . . . . . . . 313R,
. . . . . . . . 394I,
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)

Supporting Sequences HA

. . . . Milan18_2011_01_11 (
. . . . . . . . GenBank JF801862
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa11,
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa),
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))

. . . . Milan163_2011_01_14 (
. . . . . . . . GenBank JF801878
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa11,
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa),
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . HA Truncated after aa327)

. . . . UKEngland334_2010_12_15 (
. . . . . . . . GISAID EPI309641
. . . . . . . . 9 Polymorphisms (6 Amino and 3 Silent)
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa),
. . . . . . . . 100N,
. . . . . . . . 157Q mix wt,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))

. . . . UKIreland72392_2010_12_07 (
. . . . . . . . GISAID EPI309663
. . . . . . . . 10 Polymorphisms (7 Amino and 3 Silent)
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa),
. . . . . . . . 100N,
. . . . . . . . 158E mix wt,
. . . . . . . . 163T mix wt,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))

. . . . Vladivistok7_2010_12_03 (
. . . . . . . . GISAID EPI306383
. . . . . . . . 12 Polymorphisms (7 Amino and 5 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . 85A,
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn215P (CCa),
. . . . . . . . 236I,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn538F (TTt))

. . . . JapanTochigi105_2010_11_20 (
. . . . . . . . GISAID EPI305439
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 146G,
. . . . . . . . 166Q mix,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . 205W mix,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa347)

. . . . AlabamaAF2073_2010_02_14 (
. . . . . . . . GISAID EPI276240
. . . . . . . . 3 Polymorphisms (3 Amino and 0 Silent)
. . . . . . . . 59S,
. . . . . . . . 269L,
. . . . . . . . 377K,
. . . . . . . . HA Truncated after aa386)

. . . . Hawaii03_2010_02_08 (
. . . . . . . . GISAID EPI278818
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . 38G,
. . . . . . . . 59S,
. . . . . . . . 377K,
. . . . . . . . syn494E (GAa))

. . . . swThailandCU_RA75_2010_01 (
. . . . . . . . GISAID EPI255118
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . 188T,
. . . . . . . . 263D,
. . . . . . . . syn350G (GGg),
. . . . . . . . 414I,
. . . . . . . . syn484N (AAc))

. . . . KoreaDaejeon1871_2009_12_15 (
. . . . . . . . GISAID EPI254654
. . . . . . . . 4 Polymorphisms (4 Amino and 0 Silent)
. . . . . . . . 25R,
. . . . . . . . 59S,
. . . . . . . . 131P,
. . . . . . . . 158E)

. . . . TexasAF2623_2009_12_13 (
. . . . . . . . GISAID EPI281756
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 57E,
. . . . . . . . 59S,
. . . . . . . . 100N,
. . . . . . . . syn137A (GCt),
. . . . . . . . syn270I (ATc),
. . . . . . . . 377K,
. . . . . . . . HA Truncated after aa386)









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

2011-03-28

Scandinavia Accumulates Superset on Emergent 188T Background

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 Updated
2011-03-29

On 2011-03-20, the Statens Serum Institut of Copenhagen, Denmark published 6 pH1N1 sequences at GenBank sampled in a time period spanning approximately 3 weeks from late December 2010 until mid January 2011. Five of the six HA sequences demonstrate the 188T of the first pH1N1 emergent nucleotide coding having a second base revision (AcT) and two of those Denmark 188T sequences additionally carry HA 225G.

Denmark120_2010_12_20 and Denmark20_2011_01_04 with 188T and 225G demonstrate ongoing transmission of a template having 6 revisions (100N, syn179L, 188T, syn338G, syn448L, 454N) that congealed during November and December across published cases in at least nine American states and in severe and fatal UK cases. The backgrounds with 188T have exhibited experimentally and practically determined Vaccine Escape, as have backgrounds carrying 225G individually. The final silent revision at HA 448L on this particular 188T template appears to correlate with RBD revisions (190G, 221L, 224K) and to revisions at known Vaccine Escape amino acid positions (158E, 159D, 188T (AcT), 225G).



A potentially related, contemporary sequence from Sweden was sampled one day after Denmark120_2010_12_20.  SwedenHalmstad1_23F_2010_12_21, from the adjacent European geography, is the first published on this 188T background to carry HA 230I.  The Halmstad sequence also revised at a known Vaccine Escape position to 159K.  As the 188T bearing sub-clades represent over 50% of all GISAID-published, human pH1N1 sequences between October 2010 and March 2011, the "swl" lineage appears to have widespread 188T seeding that is attractant to additional polymorphic accommodation from zoonotic sources.

Though Scandinavia is now the only published geography with the polymorphic superset of 159K, 188T, 225G and 230I on similar backgrounds, GeneWurx analysis suggests that a signal with 188T, 225G and 230I has reportable probability in Scandinavia and several other regions worldwide.  Consideration must be given to this potential template (188T, 225G, 230I) also carrying a revision from aa156 to aa159.  In a parallel, transmitting sub-clade, 189T, 225G and 230I show potential for convergence and / or expansion with 165N and / or 158E.

Polymorphism jumping appears to be occurring bi-directionally between the transmitting 189T sub-clade and the emergent 188T sub-clades.

. . . . Denmark120_2010_12_20 (
. . . . . . . . HA truncated before aa1,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T [SwedenHalmstad1_23F_2010_12_21
. . . . . . . . . . . . . . . . with 100N, 159K, 230I,
. . . . . . . . . . . . . . . . . . . . syn338G, 377K,
. . . . . . . . . . . . . . . . . . . . 454N, syn537S],
. . . . . . . . 225G mix wt,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L [UKEngland4940476_2010_12_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4880378_2010_12_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . Kentucky09_2010_11_01
. . . . . . . . . . . . . . . . . . . . with 100N, 158E, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4640543_2010_11_f
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 190G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4920303_2010_11_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland142_2010_11_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland126_2010_11
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 221L, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4860049_2010_11
. . . . . . . . . . . . . . . . . . . . with 0A, 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . syn210S, syn338G, 377K,
. . . . . . . . . . . . . . . . . . . . . . . . 454N, 528I,
. . . . . . . . . . . . . . . . Hawaii08_2010_04_12
. . . . . . . . . . . . . . . . . . . . with 159D, 269V,
. . . . . . . . . . . . . . . . . . . . . . . . 312R, 313K, 377K,
. . . . . . . . . . . . . . . . Yakutsk_EAV_2009_11_18
. . . . . . . . . . . . . . . . . . . . with syn348V,
. . . . . . . . . . . . . . . . Yaroslavl_CHMV_2009_11_10_f
. . . . . . . . . . . . . . . . . . . . with 224K, 225G, syn348V, syn542S],
. . . . . . . . 454N)

. . . . Denmark20_2011_01_04 (
. . . . . . . . HA truncated before aa1,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T [SwedenHalmstad1_23F_2010_12_21
. . . . . . . . . . . . . . . . with 100N, 159K, 230I,
. . . . . . . . . . . . . . . . . . . . syn338G, 377K,
. . . . . . . . . . . . . . . . . . . . 454N, syn537S],
. . . . . . . . 225G mix wt,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L [UKEngland4940476_2010_12_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4880378_2010_12_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . Kentucky09_2010_11_01
. . . . . . . . . . . . . . . . . . . . with 100N, 158E, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4640543_2010_11_f
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 190G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4920303_2010_11_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland142_2010_11_severe
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland126_2010_11
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 221L, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . UKEngland4860049_2010_11
. . . . . . . . . . . . . . . . . . . . with 0A, 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . syn210S, syn338G, 377K,
. . . . . . . . . . . . . . . . . . . . . . . . 454N, 528I,
. . . . . . . . . . . . . . . . Hawaii08_2010_04_12
. . . . . . . . . . . . . . . . . . . . with 159D, 269V,
. . . . . . . . . . . . . . . . . . . . . . . . 312R, 313K, 377K,
. . . . . . . . . . . . . . . . Yakutsk_EAV_2009_11_18
. . . . . . . . . . . . . . . . . . . . with syn348V,
. . . . . . . . . . . . . . . . Yaroslavl_CHMV_2009_11_10_f
. . . . . . . . . . . . . . . . . . . . with 224K, 225G, syn348V, syn542S],
. . . . . . . . 454N,
. . . . . . . . syn541C)

Supporting Sequences

From GISAID database (GISAID Citation).

. . . . SwedenHalmstad1_23F_2010_12_21 (
. . . . . . . . 100N [Slovakia1625_56X_2010_03_30_xL
. . . . . . . . . . . . . . . . . . . . with 230I],
. . . . . . . . 159K [UKEngland4940476_2010_08
. . . . . . . . . . . . . . . . . . . . with 128D, 377K,
. . . . . . . . . . . . . NY3230_2010_01_25
. . . . . . . . . . . . . . . . . . . . with 100N, syn231N],
. . . . . . . . 188T,
. . . . . . . . 230I,
. . . . . . . . syn245F [RussiaBelgorod2_2010_03_15
. . . . . . . . . . . . . . . . . . . . with 158E, 225G, 230I & syn343G],
. . . . . . . . 280A [MXinDRE797_2010_TmX
. . . . . . . . . . . . . swIowa44837_1_2009_11_08_xL
. . . . . . . . . . . . . . . . . . . . with 156E, 225N, 230I & syn346G],
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S [UKEngland5040499_2010_12_f])

. . . . UKEngland142_2010_11_severe (
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L,
. . . . . . . . 454N)

. . . . UKEngland126_2010_11 (
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 221L,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L,
. . . . . . . . 454N)

. . . . UKEngland4860049_2010_11 (
. . . . . . . . 0A,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn210S,
. . . . . . . . syn338G,
. . . . . . . . 377K,
. . . . . . . . syn448L,
. . . . . . . . 454N,
. . . . . . . . 528I)

. . . . Hawaii08_2010_04_12
. . . . . . . . 159D mix wt,
. . . . . . . . 269V,
. . . . . . . . syn288A,
. . . . . . . . 312R,
. . . . . . . . 313K,
. . . . . . . . 377K,
. . . . . . . . syn448L [England4940476_2010_12,
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . Kentucky09_2010_11_01
. . . . . . . . . . . . . . . . . . . . with 100N, 158E, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . England4640543_2010_11_f
. . . . . . . . . . . . . . . . . . . . with 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . . . . . . . . . 190G, syn338G, 377K, 454N,
. . . . . . . . . . . . . . . . Yakutsk_EAV_2009_11_18
. . . . . . . . . . . . . . . . . . . . with syn348V,
. . . . . . . . . . . . . . . . Yaroslavl_CHMV_2009_11_10_f
. . . . . . . . . . . . . . . . . . . . with 224K, 225G, syn348V, syn542S])



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

2010-08-31

HA 230I RBS Polymorphism Potential for Europe

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

For those who are following the prediction on February 25, 2010, the pandemic reservoir now shows multiple instances of multiple encodings for 230I.  Model adjustment and data transparency allowed a second set of detailed geographic predictions on 2010-08-09 that have also found traction.

The 230I bearing sequences meeting the prediction are documented in the detailed discussion on Vaccine Escape that demonstrates a 100% change rate in the pandemic influenza (pH1N1) reservoir at the critical HA genetics range between amino acid positions 186 and 248.  89% of the amino acid positions have notated revisions.

Expectations for the M230I polymorphism, that first came to our notice for zoonotic concern on the H5N1 human fatality cluster, have now been revised based on the most current public data.  The GeneWurx model approximates that HA 230I will appear in the PF11 RBS according to the following geographic probabilities.

  • 75% probability in Germany sampled by 2010-12-01.
  • 75% probability in Spain sampled by 2010-12-01.
  • 85% probability sampled by 2010-12-01 in one of:
    • Denmark
    • Norway
    • Sweden
  • 5% or less probability of HA 230I within 60 days of conserving across PF11.
  • 7% probability of HA 230I within 180 days of conserving on one or more Hydrae.
This HA polymorphism guided an investigation suggesting that  anti-viral resistance from the NA H275Y revision is not the only genetic concern with over-usage.  Anti-viral drug usage may drive 230I genetic acquisition, with a higher potential among children and young adults (0-24 years old). The sparsity of complete sequences, discounted by the lack of required meta-data, allows only a rough postulation on the mechanism.

An accelerated viral self-revision, subsequently moving toward M230I, may be modulated by the substantially higher rates of host exposure in the lower age brackets. Additionally, that group’s multiplicity of exposure to a wider variation of influenza strains may factor into the host response/viral revision equation. In plain terms, the viral reservoir is being forced toward hard labour in order to infect and re-infect the youth.

Just as hard work builds muscle, viral exertion against a complex host response challenges the reservoir subset to revise toward an optimal solution. 230I is an excellent and proven tertiary response for a virus on this type of offensive.

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



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

2010-08-12

Sweden Fatality Sequence Demonstrates Role of Scandinavia in FlightPath Between US and Russia

Last Updated
2011-03-29

Clinical outcome was provided by the Swedish Institute for Infectious Disease Control in deposits at GISAID made between January and March of 2010.  Three HA sequences are marked as "post-mortem" and/or "deceased". 

The October and December sequences carry 225E with a minimal number of changes.

The fatal, cross-linked November case from Orebro shows a potentially zoonotic silent 177L-forming Single Nucleotide Polymorphism (SNP) with a notable FlightPath.  The synonymous revision had an early appearance in Wisconsin, is well-represented on the population of 9 cross-linked Russian fatalities and has recently traveled to New York and Nagasaki.

. . . . SwedenOrebro1_2009_11_02_xL_f  (
. . . . . . . . syn177L [H3N8, H6, H7N7],
. . . . . . . . . . . . . . [NagasakiHA_10_30_2010_03_29 with 513V, 550K,
. . . . . . . . . . . . . . NagasakiHA_10_27_2010_03_15 with 513V, 550K,
. . . . . . . . . . . . . . NY3230_2010_01_25 with syn213F,
. . . . . . . . . . . . . . Kansas25_2009_12_07 with 50A,
. . . . . . . . . . . . . . Indiana21_2009_12_01 with 212E, 313K,
. . . . . . . . . . . . . . SwedenGothenburg2_2009_12_01_xL with 146G,
. . . . . . . . . . . . . . Tambov_LLA_2009_11_30_xL_f with 225G,
. . . . . . . . . . . . . . Perm01_2009_11_25_xL_f,
. . . . . . . . . . . . . . MoscowOb_ZNF_2009_11_24_xL_f,
. . . . . . . . . . . . . . Ivanovo_KOE_2009_11_25_xL_f,
. . . . . . . . . . . . . . Astrakhan_CHRM_2009_11_24_xL_f,
. . . . . . . . . . . . . . GreeceThessaloniki2812_2009_11_22,
. . . . . . . . . . . . . . Ivanovo_STV1_2009_11_21 with 225G,
. . . . . . . . . . . . . . NorwayOslo110_2009_11_10,
. . . . . . . . . . . . . . MoscowOb_STV_2009_11_09_f with 225N,
. . . . . . . . . . . . . . GermanyNiedersachsen352_2009_11_05,
. . . . . . . . . . . . . . MoscowOb_OAM_2009_11_02_xL_f with 225G,
. . . . . . . . . . . . . . MoscowOb_DEI_2009_11_xL_f with 225G,
. . . . . . . . . . . . . . Ivanovo_AMV_2009_11_xL_f with 225G,
. . . . . . . . . . . . . . BelgiumBrussels106_2009_10_29,
. . . . . . . . . . . . . . Moscow_BVA_2009_10_24_xL_f with 225G,
. . . . . . . . . . . . . . SwedenUmea8_2009_10_07 with 0I, 244I,
. . . . . . . . . . . . . . Norway3364_2_2009_09_08_xL,
. . . . . . . . . . . . . . DenmarkAarhus82_2009_xL,
. . . . . . . . . . . . . . Orenburg_VNV_2009_08_06_xL,
. . . . . . . . . . . . . . England2800004_2009_07,
. . . . . . . . . . . . . . WiscD0008_2009_06_04],
. . . . . . . . 324I,
. . . . . . . . syn413K [H9N2])

. . . . SwedenStockholm96_2009_10_04_f  (
. . . . . . . . #1T,
. . . . . . . . 225E,
. . . . . . . . HA truncated after aa251)

. . . . SwedenUmea13_2009_12_09_f  (
. . . . . . . . #7A,
. . . . . . . . 140S,
. . . . . . . . 225E)


Two sequences from the US, NY3230_2010_01_25 and Indiana21_2009_12_01, provide potential for interchange between the Russian / Eastern European sequences carrying syn177L and the recently profiled emerging sub-clade from the US and the Ukraine during April to June 2010.

Please refer to additional studies for further genetic analyses, including the survey on amino acid revisions potentially related to Vaccine Escape.  A hyper-morphic, TamiFlu-resistant sequence from the state of Washington in Spring 2010 has recently been profiled with similar zoonotic influences.

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

2010-03-22

Cross-Linked Background Includes 226R Strain from India and Sweden Entry with novel 190Y

Cross-Linked Silent HA and NA Polymorphisms Correlated with Fatal 225G Cases in the Ukraine and Russia
  • HA:syn413K encoded from A1281G, AAa->AAg
  • NA:syn407V encoded from T1221C, GTt->GTc
 PF11 Sequences Demonstrating Cross Segment Linkage
  • 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 India BloreNIV236 with 226R, syn372Q, 454N and 550T *
  • HA and NA Sweden Stockholm31
  • Sweden Malmoe1 from 2010 with 190Y, 324I and 377K *
  • 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 
98 sequences have encircled the globe as of 2010-03-19 * with high fidelity carrying a cross-segment paired set of background markers matching and contributing to fatal cases in the Ukraine and Russia.  225G appears in 14 on this background; 225N once and 225E precisely zero.  The first occasion of 226R now enters our list retrospectively due to sequence release delay with a June 2009 case from India.

These 2 newest entries represent a very early case of ΣPF11 in an Indian individual who travelled extensively and a very recent case in Sweden from January 2010. All data guides us to the position that this pandemic reservoir is not approaching stasis. The background continues to widen within the existing clades demonstrating that ΣPF11 is far from reaching Omega status.

Areas covered include Texas (3), the Northeastern United States (5), Kentucky, Indiana, North Carolina (5), China (2), Singapore, India, Australia (2), the Ukraine (23), Moldova (5), Russia (18), Iraq (3), Denmark(3), Norway (2), Sweden (3), 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:


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

GeneWurx.com