Prediction Demonstrated of Antigenic Dual Geography sH3N2 HA 140K

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 Excel for completeness in citation.

Publish Date : 2013-12-02
Last Update : 2013-12-04

Map - Dual Geography Prediction

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2 Predicted Human Sequences

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The United States CDC and the UK National Institute for Medical Research published sequences at GISAID respectively on 2013-06-21 (CDC) and 2013-06-26 (NIMR) that fulfill the dual geography genetic change and timing of the GeneWurx spread prediction published on 2013-02-08 titled sH3N2 HA 140K Antigen Polymorphism Potential in Europe and North America.

Antigenic Variance

sH3N2 Antigen Revision Demonstrated As Predicted Sample Date Name Antigen Revision ID  2013-04-24   Alaska04_C2_44M  HA 140K  EPI459829   2013-03-12   RussiaSamara73_C1St1_17F  HA 140K  EPI460558

The Alaska04_C2_44M_2013_04_24 sequence was antigenically characterised as a Victoria361-like vaccine match.

Vaccine Candidate Investigation

On 2013-12-02 the United States CDC produced 3 lab-derived, HA 140K sequences dated 2013-11-29 and 2013-12-02 (2) at GISAID that originated at New York Medical College and are coded similarly to previous Investigational Vaccine Candidates (X-233 & X-233A).  The 3 lab-developed sequences appear to be based on the Hemagglutinin & Neuraminidase of the fixed form derived / purified from an early ambiguous HA 140K emergence, A/New York/39/2012.

That New York sample taken on 2012-10-20 was published with a submission date and update date of 2012-12-07 on a C1 passage with HA 140I, then on an E3 passage with ambiguity at HA aa140.  Those C1 and E3 passages were each antigenically characterised as Victoria361-like vaccine matches, although that E3 passage showed some trace of ambiguity resolving to HA 140K.

In a publication dated 2013-03-14, an E4 passage derived the HA 140K.  An E5 passage of A/New York/39/2012 with ambiguity resolving to HA 140K was added to GISAID today, 2013-12-02, by the United States CDC to join the outcomes of various other passage strategies for a total of 9 sequences on deposit from this New York sample.

Vaccine Candidate Investigation

sH3N2 Investigational NewYork39_2012_10_20 Passage Strategies Publish Date Name aa140 Antigen ID  2013-12-02   NewYork39_EXIR_5M_X233A_2012_10_20  HA 140K  EPI490080   2013-12-02   NewYork39_EXIR_5M_X233_2012_10_20  HA 140K  EPI490077   2013-11-29   NewYork39_E4E8E1_5M_X233_2012_10_20  HA 140K  EPI489319   2013-12-02   NewYork39_E5_5M_2012_10_20  HA 140K mix wt  EPI490093   2013-05-08   NewYork39_C2_5M_2012_10_20  HA 140I  EPI445712   2013-03-14   NewYork39_E4_5M_2012_10_20  HA 140K  EPI436261   2013-02-25   NewYork39_C3_5M_2012_10_20  HA 140I  EPI426140   2012-12-07   NewYork39_E3_5M_2012_10_20  HA 140K mix wt  EPI404965   2012-12-07   NewYork39_C1_5M_2012_10_20  HA 140I  EPI404927

MetaData

Our researchers very much appreciate that age and gender information are annotated for each base HA 140K sequence via the originating / submitting organisation's chain of custody.

Although 1 of the 2 HA 140K prediction demonstration sequences was updated subsequent to the original submission, no clinical progression, treatment annotation or clinical outcome has yet been made public corresponding to these very important cases that originated respectively from the Alaska State Virology Lab and WHO National Influenza Centre of Saint Petersburg, Russia.

HA Polymorphisms

. . . . Alaska04_C2_44M_2013_04_24 (

. . . . . . . . A/Alaska/04/2013
. . . . . . . . Emergent H7N9 Correlation HA 131A

. . . . . . . . GISAID HA EPI459829

. . . . . . . . GISAID Isolate EPI_ISL_143267

. . . . . . . . 18 Polymorphisms (10 Amino and 8 Silent)

. . . . . . . . #7Y,

. . . . . . . . syn8N (AAt),

. . . . . . . . 33R,

. . . . . . . . syn79F (TTt),

. . . . . . . . 131A [Emergent H7N9 wild type],

. . . . . . . . 140K,

. . . . . . . . 145S,

. . . . . . . . 156H,

. . . . . . . . 186G,

. . . . . . . . 190D,

. . . . . . . . syn215P (CCa),

. . . . . . . . 278K,

. . . . . . . . syn402V (GTa),

. . . . . . . . syn455L (CTg),

. . . . . . . . syn481I (ATa),

. . . . . . . . 489N,

. . . . . . . . syn490V (GTg),

. . . . . . . . syn492R (AGg))

. . . . RussiaSamara73_C1St1_17F_2013_03_12 (

. . . . . . . . A/Samara/73/2013

. . . . . . . . Emergent H7N9 Correlation HA 128A
. . . . . . . . GISAID HA EPI460558

. . . . . . . . GISAID Isolate EPI_ISL_143568

. . . . . . . . 19 Polymorphisms (10 Amino and 9 Silent)

. . . . . . . . #7Y,

. . . . . . . . syn8N (AAt),

. . . . . . . . 33R,

. . . . . . . . syn36V (GTc),

. . . . . . . . syn79F (TTt),

. . . . . . . . 128A [Emergent H7N9 Count 02:
. . . . . . . . . . . . . . . HongKong5942_M_36F_2013_11_30_s

. . . . . . . . . . . . . . . . . . . Deposit Report
. . . . . . . . . . . . . . . . . . . GISAID HA EPI490882

. . . . . . . . . . . . . . . . . . . GISAID Isolate EPI_ISL_151417,

. . . . . . . . . . . . . . . ChinaGuangdongHuizhou1_51F_2013_08_10_s
. . . . . . . . . . . . . . . . . . . Deposit Report

. . . . . . . . . . . . . . . . . . . GISAID HA EPI476697

. . . . . . . . . . . . . . . . . . . GISAID Isolate EPI_ISL_148417],

. . . . . . . . 140K,

. . . . . . . . 142G,

. . . . . . . . 145S,

. . . . . . . . 156H,

. . . . . . . . syn175D (GAt),

. . . . . . . . 186G,

. . . . . . . . 190D,

. . . . . . . . 278K,

. . . . . . . . syn402V (GTa),

. . . . . . . . syn416T (ACa),

. . . . . . . . syn455L (CTg),

. . . . . . . . syn479G (GGg),

. . . . . . . . syn492R (AGg))

NA Polymorphisms

. . . . Alaska04_C2_44M_2013_04_24 (

. . . . . . . . A/Alaska/04/2013

. . . . . . . . GISAID NA EPI459828

. . . . . . . . GISAID Isolate EPI_ISL_143267

. . . . . . . . 15 Polymorphisms (6 Amino and 9 Silent)

. . . . . . . . syn11G (GGc),

. . . . . . . . syn18S (TCc),

. . . . . . . . syn28I (ATt),

. . . . . . . . syn68L (tTa),

. . . . . . . . syn106I (ATt),

. . . . . . . . 151N mix wt,

. . . . . . . . syn167F (TTc),

. . . . . . . . 197N,

. . . . . . . . 221D,

. . . . . . . . syn248G (GGg),

. . . . . . . . 258E,

. . . . . . . . syn300R (cGG),

. . . . . . . . 329N,

. . . . . . . . 392T,

. . . . . . . . syn439T (ACc))

. . . . RussiaSamara73_C1St1_17F_2013_03_12 (

. . . . . . . . A/Samara/73/2013

. . . . . . . . GISAID NA EPI460559

. . . . . . . . GISAID Isolate EPI_ISL_143568

. . . . . . . . 13 Polymorphisms (4 Amino and 9 Silent)

. . . . . . . . syn11G (GGc),

. . . . . . . . syn18S (TCc),

. . . . . . . . 64K,

. . . . . . . . syn106I (ATt),

. . . . . . . . syn108L (CTa),

. . . . . . . . syn128K (AAa),

. . . . . . . . syn234N (AAc),

. . . . . . . . 258E,

. . . . . . . . syn300R (cGG),

. . . . . . . . 329N,

. . . . . . . . syn395Q (CAg),

. . . . . . . . 427T,

. . . . . . . . syn439T (ACc))

Supporting Sequences

HA Polymorphisms

. . . . NewYork39_EXIR_5M_X233A_2012_10_20 (

. . . . . . . . A/New York/39/2012 X-233A

. . . . . . . . Original Submission: 2013-12-02

. . . . . . . . GISAID HA EPI490080

. . . . . . . . GISAID Isolate EPI_ISL_151399

. . . . . . . . 19 Polymorphisms (11 Amino and 8 Silent)

. . . . . . . . #7Y,

. . . . . . . . syn8N (AAt),

. . . . . . . . 33R,

. . . . . . . . syn79F (TTt),

. . . . . . . . 128A,

. . . . . . . . 140K,

. . . . . . . . 142G,

. . . . . . . . 145S,

. . . . . . . . 156H,

. . . . . . . . syn172E (GAg),

. . . . . . . . 186G,

. . . . . . . . 190D,

. . . . . . . . 194P,

. . . . . . . . 278K,

. . . . . . . . syn281C (TGt),

. . . . . . . . syn402V (GTa),

. . . . . . . . syn416T (ACa),

. . . . . . . . syn455L (CTg),

. . . . . . . . syn492R (AGg))

. . . . NewYork39_EXIR_5M_X233_2012_10_20 (

. . . . . . . . A/New York/39/2012 X-233

. . . . . . . . Original Submission: 2013-12-02

. . . . . . . . GISAID HA EPI490077

. . . . . . . . GISAID Isolate EPI_ISL_151398

. . . . . . . . 19 Polymorphisms (11 Amino and 8 Silent)

. . . . . . . . #7Y,

. . . . . . . . syn8N (AAt),

. . . . . . . . 33R,

. . . . . . . . syn79F (TTt),

. . . . . . . . 128A,

. . . . . . . . 140K,

. . . . . . . . 142G,

. . . . . . . . 145S,

. . . . . . . . 156H,

. . . . . . . . syn172E (GAg),

. . . . . . . . 186G,

. . . . . . . . 190D,

. . . . . . . . 194P,

. . . . . . . . 278K,

. . . . . . . . syn281C (TGt),

. . . . . . . . syn402V (GTa),

. . . . . . . . syn416T (ACa),

. . . . . . . . syn455L (CTg),

. . . . . . . . syn492R (AGg))

. . . . NewYork39_E4E8E1_5M_X233_2012_10_20 (

. . . . . . . . A/New York/39/2012 X-233

. . . . . . . . Original Submission: 2013-11-29

. . . . . . . . GISAID HA EPI489319

. . . . . . . . GISAID Isolate EPI_ISL_151026

. . . . . . . . 19 Polymorphisms (11 Amino and 8 Silent)

. . . . . . . . #7Y,

. . . . . . . . syn8N (AAt),

. . . . . . . . 33R,

. . . . . . . . syn79F (TTt),

. . . . . . . . 128A,

. . . . . . . . 140K,

. . . . . . . . 142G,

. . . . . . . . 145S,

. . . . . . . . 156H,

. . . . . . . . syn172E (GAg),

. . . . . . . . 186G,

. . . . . . . . 190D,

. . . . . . . . 194P,

. . . . . . . . 278K,

. . . . . . . . syn281C (TGt),

. . . . . . . . syn402V (GTa),

. . . . . . . . syn416T (ACa),

. . . . . . . . syn455L (CTg),

. . . . . . . . syn492R (AGg))

. . . . NewYork39_E5_5M_2012_10_20 (

. . . . . . . . A/New York/39/2012

. . . . . . . . Original Submission: 2013-12-02

. . . . . . . . GISAID HA EPI490093

. . . . . . . . GISAID Isolate EPI_ISL_151400

. . . . . . . . 19 Polymorphisms (11 Amino and 8 Silent)

. . . . . . . . #7Y,

. . . . . . . . syn8N (AAt),

. . . . . . . . 33R,

. . . . . . . . syn79F (TTt),

. . . . . . . . 128A,

. . . . . . . . 140K mix wt,

. . . . . . . . 142G,

. . . . . . . . 145S,

. . . . . . . . 156H,

. . . . . . . . syn172E (GAg),

. . . . . . . . 186G,

. . . . . . . . 190D,

. . . . . . . . 194P mix wt,

. . . . . . . . 278K,

. . . . . . . . syn281C (TGt),

. . . . . . . . syn402V (GTa),

. . . . . . . . syn416T (ACa),

. . . . . . . . syn455L (CTg),

. . . . . . . . syn492R (AGg))

. . . . NewYork39_C2_5M_2012_10_20 (

. . . . . . . . A/New York/39/2012

. . . . . . . . Original Submission: 2013-05-08

. . . . . . . . GISAID HA EPI445712

. . . . . . . . GISAID Isolate EPI_ISL_140279

. . . . . . . . 17 Polymorphisms (9 Amino and 8 Silent)

. . . . . . . . #7Y,

. . . . . . . . syn8N (AAt),

. . . . . . . . 33R,

. . . . . . . . syn79F (TTt),

. . . . . . . . 128A,

. . . . . . . . 142G,

. . . . . . . . 145S,

. . . . . . . . 156H,

. . . . . . . . syn172E (GAg),

. . . . . . . . 186G,

. . . . . . . . 190D,

. . . . . . . . 278K,

. . . . . . . . syn281C (TGt),

. . . . . . . . syn402V (GTa),

. . . . . . . . syn416T (ACa),

. . . . . . . . syn455L (CTg),

. . . . . . . . syn492R (AGg))

. . . . NewYork39_E4_5M_2012_10_20 (

. . . . . . . . A/New York/39/2012

. . . . . . . . Original Submission: 2013-03-14

. . . . . . . . GISAID HA EPI436261

. . . . . . . . GISAID Isolate EPI_ISL_138001

. . . . . . . . 19 Polymorphisms (11 Amino and 8 Silent)

. . . . . . . . #7Y,

. . . . . . . . syn8N (AAt),

. . . . . . . . 33R,

. . . . . . . . syn79F (TTt),

. . . . . . . . 128A,

. . . . . . . . 140K,

. . . . . . . . 142G,

. . . . . . . . 145S,

. . . . . . . . 156H,

. . . . . . . . syn172E (GAg),

. . . . . . . . 186G,

. . . . . . . . 190D,

. . . . . . . . 194P mix wt,

. . . . . . . . 278K,

. . . . . . . . syn281C (TGt),

. . . . . . . . syn402V (GTa),

. . . . . . . . syn416T (ACa),

. . . . . . . . syn455L (CTg),

. . . . . . . . syn492R (AGg))

. . . . NewYork39_C3_5M_2012_10_20 (

. . . . . . . . A/New York/39/2012

. . . . . . . . Original Submission: 2013-02-25

. . . . . . . . GISAID HA EPI426140

. . . . . . . . GISAID Isolate EPI_ISL_136409

. . . . . . . . 17 Polymorphisms (9 Amino and 8 Silent)

. . . . . . . . #7Y,

. . . . . . . . syn8N (AAt),

. . . . . . . . 33R,

. . . . . . . . syn79F (TTt),

. . . . . . . . 128A,

. . . . . . . . 142G,

. . . . . . . . 145S,

. . . . . . . . 156H,

. . . . . . . . syn172E (GAg),

. . . . . . . . 186G,

. . . . . . . . 190D,

. . . . . . . . 278K,

. . . . . . . . syn281C (TGt),

. . . . . . . . syn402V (GTa),

. . . . . . . . syn416T (ACa),

. . . . . . . . syn455L (CTg),

. . . . . . . . syn492R (AGg))

. . . . NewYork39_E3_5M_2012_10_20 (

. . . . . . . . A/New York/39/2012

. . . . . . . . Original Submission: 2012-12-07

. . . . . . . . GISAID HA EPI404965

. . . . . . . . GISAID Isolate EPI_ISL_131823

. . . . . . . . 19 Polymorphisms (11 Amino and 8 Silent)

. . . . . . . . #7Y,

. . . . . . . . syn8N (AAt),

. . . . . . . . 33R,

. . . . . . . . syn79F (TTt),

. . . . . . . . 128A,

. . . . . . . . 140K mix wt,

. . . . . . . . 142G,

. . . . . . . . 145S,

. . . . . . . . 156H,

. . . . . . . . syn172E (GAg),

. . . . . . . . 186G mix wt,

. . . . . . . . 190D,

. . . . . . . . 219Y mix wt,

. . . . . . . . 278K,

. . . . . . . . syn281C (TGt),

. . . . . . . . syn402V (GTa),

. . . . . . . . syn416T (ACa),

. . . . . . . . syn455L (CTg),

. . . . . . . . syn492R (AGg))

. . . . NewYork39_C1_5M_2012_10_20 (

. . . . . . . . A/New York/39/2012

. . . . . . . . Original Submission: 2012-12-07

. . . . . . . . GISAID HA EPI404927

. . . . . . . . GISAID Isolate EPI_ISL_131810

. . . . . . . . 17 Polymorphisms (9 Amino and 8 Silent)

. . . . . . . . #7Y,

. . . . . . . . syn8N (AAt),

. . . . . . . . 33R,

. . . . . . . . syn79F (TTt),

. . . . . . . . 128A,

. . . . . . . . 142G,

. . . . . . . . 145S,

. . . . . . . . 156H,

. . . . . . . . syn172E (GAg),

. . . . . . . . 186G,

. . . . . . . . 190D,

. . . . . . . . 278K,

. . . . . . . . syn281C (TGt),

. . . . . . . . syn402V (GTa),

. . . . . . . . syn416T (ACa),

. . . . . . . . syn455L (CTg),

. . . . . . . . syn492R (AGg))

NA Polymorphisms

. . . . NewYork39_EXIR_5M_X233A_2012_10_20 (

. . . . . . . . A/New York/39/2012 X-233A

. . . . . . . . Original Submission: 2013-12-02

. . . . . . . . GISAID NA EPI490079

. . . . . . . . GISAID Isolate EPI_ISL_151399

. . . . . . . . 10 Polymorphisms (3 Amino and 7 Silent)

. . . . . . . . syn11G (GGc),

. . . . . . . . syn18S (TCc),

. . . . . . . . 43D,

. . . . . . . . syn106I (ATt),

. . . . . . . . 258E,

. . . . . . . . syn275V (GTt),

. . . . . . . . syn300R (cGG),

. . . . . . . . 329N,

. . . . . . . . syn439T (ACc),

. . . . . . . . syn465N (AAc))

. . . . NewYork39_EXIR_5M_X233_2012_10_20 (

. . . . . . . . A/New York/39/2012 X-233

. . . . . . . . Original Submission: 2013-12-02

. . . . . . . . GISAID NA EPI490076

. . . . . . . . GISAID Isolate EPI_ISL_151398

. . . . . . . . 10 Polymorphisms (3 Amino and 7 Silent)

. . . . . . . . syn11G (GGc),

. . . . . . . . syn18S (TCc),

. . . . . . . . 43D,

. . . . . . . . syn106I (ATt),

. . . . . . . . 258E,

. . . . . . . . syn275V (GTt),

. . . . . . . . syn300R (cGG),

. . . . . . . . 329N,

. . . . . . . . syn439T (ACc),

. . . . . . . . syn465N (AAc))

. . . . NewYork39_E5_5M_2012_10_20 (

. . . . . . . . A/New York/39/2012

. . . . . . . . Original Submission: 2013-12-02

. . . . . . . . GISAID NA EPI490092

. . . . . . . . GISAID Isolate EPI_ISL_151400

. . . . . . . . 10 Polymorphisms (3 Amino and 7 Silent)

. . . . . . . . syn11G (GGc),

. . . . . . . . syn18S (TCc),

. . . . . . . . 43D,

. . . . . . . . syn106I (ATt),

. . . . . . . . 258E,

. . . . . . . . syn275V (GTt),

. . . . . . . . syn300R (cGG),

. . . . . . . . 329N,

. . . . . . . . syn439T (ACc),

. . . . . . . . syn465N (AAc))

. . . . NewYork39_C2_5M_2012_10_20 (

. . . . . . . . A/New York/39/2012

. . . . . . . . Original Submission: 2013-05-08

. . . . . . . . GISAID NA EPI445711

. . . . . . . . GISAID Isolate EPI_ISL_140279

. . . . . . . . 11 Polymorphisms (4 Amino and 7 Silent)

. . . . . . . . syn11G (GGc),

. . . . . . . . syn18S (TCc),

. . . . . . . . 43D,

. . . . . . . . syn106I (ATt),

. . . . . . . . 151N mix wt,

. . . . . . . . 258E,

. . . . . . . . syn275V (GTt),

. . . . . . . . syn300R (cGG),

. . . . . . . . 329N,

. . . . . . . . syn439T (ACc),

. . . . . . . . syn465N (AAc))

. . . . NewYork39_E4_5M_2012_10_20 (

. . . . . . . . A/New York/39/2012

. . . . . . . . Original Submission: 2013-03-14

. . . . . . . . GISAID NA EPI436260

. . . . . . . . GISAID Isolate EPI_ISL_138001

. . . . . . . . 10 Polymorphisms (3 Amino and 7 Silent)

. . . . . . . . syn11G (GGc),

. . . . . . . . syn18S (TCc),

. . . . . . . . 43D,

. . . . . . . . syn106I (ATt),

. . . . . . . . 258E,

. . . . . . . . syn275V (GTt),

. . . . . . . . syn300R (cGG),

. . . . . . . . 329N,

. . . . . . . . syn439T (ACc),

. . . . . . . . syn465N (AAc))

. . . . NewYork39_C3_5M_2012_10_20 (

. . . . . . . . A/New York/39/2012

. . . . . . . . Original Submission: 2013-02-25

. . . . . . . . GISAID NA EPI465202

. . . . . . . . GISAID Isolate EPI_ISL_136409

. . . . . . . . 11 Polymorphisms (4 Amino and 7 Silent)

. . . . . . . . syn11G (GGc),

. . . . . . . . syn18S (TCc),

. . . . . . . . 43D,

. . . . . . . . syn106I (ATt),

. . . . . . . . 151N mix wt,

. . . . . . . . 258E,

. . . . . . . . syn275V (GTt),

. . . . . . . . syn300R (cGG),

. . . . . . . . 329N,

. . . . . . . . syn439T (ACc),

. . . . . . . . syn465N (AAc))

. . . . NewYork39_E3_5M_2012_10_20 (

. . . . . . . . A/New York/39/2012

. . . . . . . . Original Submission: 2012-12-07

. . . . . . . . GISAID NA EPI404964

. . . . . . . . GISAID Isolate EPI_ISL_131823

. . . . . . . . 11 Polymorphisms (3 Amino and 8 Silent)

. . . . . . . . syn11G (GGc),

. . . . . . . . syn18S (TCc),

. . . . . . . . 43D,

. . . . . . . . syn106I (ATt),

. . . . . . . . syn116V (GTa) mix wt,

. . . . . . . . 258E,

. . . . . . . . syn275V (GTt),

. . . . . . . . syn300R (cGG),

. . . . . . . . 329N,

. . . . . . . . syn439T (ACc),

. . . . . . . . syn465N (AAc))

. . . . NewYork39_C1_5M_2012_10_20 (

. . . . . . . . A/New York/39/2012

. . . . . . . . Original Submission: 2012-12-07

. . . . . . . . GISAID NA EPI404926

. . . . . . . . GISAID Isolate EPI_ISL_131810

. . . . . . . . 10 Polymorphisms (3 Amino and 7 Silent)

. . . . . . . . syn11G (GGc),

. . . . . . . . syn18S (TCc),

. . . . . . . . 43D,

. . . . . . . . syn106I (ATt),

. . . . . . . . 258E,

. . . . . . . . syn275V (GTt),

. . . . . . . . syn300R (cGG),

. . . . . . . . 329N,

. . . . . . . . syn439T (ACc),

. . . . . . . . syn465N (AAc))

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sH3N2 Influenza Hemagglutinin & Neuraminidase Segments elucidated at 2013-12-02-23_34_14_375380 by GeneWurx see.PolyDetector v0, Copyright 2007-2013.
Supporting Influenza HA & NA Segments elucidated at 2013-12-03-03_05_27_920970 by GeneWurx see.PolyDetector v0, Copyright 2007-2013.

Publication Copyright 2007-2013 GeneWurx.com  · All Rights Reserved.

H5N1 and 1918 Receptor Binding Domain Change, HA 225G, Emerges On Two Sub-Clades in Spain

Spain deposited 239 sequences today at GenBank.

A/Catalonia/NS1706, sampled on 2009-07-29, Segment 4 (HA) and Segment 6 (NA)
A/Catalonia/NS2001, sampled on 2009-08-03, Segment 4 (HA) and Segment 6 (NA)
A/Catalonia/NS2008, sampled on 2009-08-03, Segment 4 (HA) and Segment 6 (NA)

225G is found on these 3 Spanish Hemagglutinins as in the 2 Sao Paulo cases during the same late July to early August timeframe.  On the CatNS1706 specimen, 206S is paired with the 225G; whereas, the Brasilian deaths were 206T and 225G similar to CatNS2001 and CatNS2008.  During the same timeframe, two cities more than 5,000 miles distant with an ocean between them each have emergence of multiple novel sub-clades for their geography related to the Receptor Binding Domain residue 225.  Consider seasonality and your puzzlement is enhanced.

225G is consensus for H5N1, is carried on NewYork1918 and only appears in 8 other PF11 sequences across the US and Mexico.

SaoPaulo53206
SaoPaulo53225
MX3955
MXInDRE4114
NY04
GA01
TX05
TX11

225X is demonstrated several times in the US proximal to 225G in area and time.

NY11
NY31
TX10
CA13
NE02

CatNS2001 and CatNS2008 also feature HA 298V, a potential reversion to swine sequences or to 2008 Seasonal.  Because 206T is featured in these two sequences and 206T is exclusive of 296H, we may perhaps postulate a secondary acquisition pathway for an unidentified human-fit, trait-enhancing domain (HA296:301). 

Three additional sequences in this deposit carry the pair of 206T and 298V:

• A/Catalonia/S1237, HA, sampled 2009-08-13
• A/Catalonia/S1248, HA, sampled 2009-08-18
• A/Catalonia/S1286, HA, sampled 2009-08-25 

All 5 of these Catalonia 298V specimens carry a 225 polymorphism, either 225E or 225G.

An Intra-Segment Exclusivity exists within the Catalonia specimens between 206S and 225E.  24 of 25 Catalonia 225E specimens carry 206T, all but the unusual CatS1161 with 206A.

Neuraminidase Quadruple Combination

• CatNS1706 = 106V, 248N, 275H, 286G 
• CatNS2001 = 106I, 248D, 275H, 286S
• CatNS2008 = 106I, 248D, 275H, 286S
• CatNS1237 = 106I, 248D, 275H, 286S
• CatNS1248 = 106I, 248D, 275H, 286S
• CatNS1286 = 106I, 248D, 275H, 286S 

NA 286G appears on 30 GenBank specimens within ΣPF11, 24 of them from Catalonia. 

Non-Random Acquisition Acceleration appears to be underway in potential trait-enhancing domains of both Antigen segments.  Influenza Flux is a two way street with clearly defined lanes and many points of ingress.

The Hydra Effect is demonstrated in the phylogenic trees of Brasil and Spain.  When your tree is all branches with only a few leaves at each tip, you aren’t going to get much protection from the sun unless you decided very early to be standing on just the right spot when the perfect light of noon arrives.

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H5N1 Coding from 2009 Egypt Toddler Cases enters PF11 Reservoir via Japan, NA 450G

A/Shizuoka/793 was deposited yesterday at GenBank with Segment 4 (HA) and Segment 6 (NA) from a sample taken 2009-06-15.

Influenza Flux is at work demonstrating increasing Antigenic Diversity.  The Japanese geography continues to produce genetically diverse PF11 strains with two significantly variant sub-clades represented in the two sequences deposited yesterday from the Shizuoka Prefecture. 

Shizuoka793 is unique within ΣPF11 for several reasons.  Though the Neuraminidase gene segment is identical at 1408 of 1410 residues to most recent geographically proximal Japan sequences and many NY specimens, the two exceptions provide us an exercise in origins:

• A1028C coding for A343E (Glutamate) 
• G1348A coding for S450G (Glycine)

Neither of these polymorphisms appear to have precedent within ΣPF11 and, as yet, we have not identified a donor candidate within the H1N1, H3N2, H1N2, H5N1 or H5N2 reservoirs for the NA:343E.  450G, on the other hand, has a lineage that is of interest considering the risk groups that we are seeing at the moment with this pandemic.

450G found on the pandemic Shizuoka793 in mid-June appears in low density among several serotypes of human Influenza specimens worldwide at GenBank and 18 are H5N1 specimens collected and sequenced by the NAMRU-3 team in Egypt between January and June 2009, immediately prior to the Shizuoka infection.  16 of those patients were under the age of 5 and geographically dispersed. 

Other recent matches are 7 H3N2 Seasonal 2009 cases, 17 H3N2 Seasonal 2008 cases, 5 H1N1 Seasonal 2008 cases, 13 H1N1 Seasonal 2007 cases, 11 H1N1 Seasonal 2006 cases and a swine farm worker from Iowa in 2005.  Though the Glycine at 450 is an uncommon Human Influenza polymorphism, the coding appears to be easily donated, moving between Avian, Swine and Human species on H5N1, H3N2 and H1N1 serotypes.  Clinical data on the Shizuoka case and the H5N1 infected toddlers would allow valuable insight.

The Neuraminidase Quadruple Combination on this sequence is 106I, 248D, 275H, 286S.

The Shizuoka793 Hemagglutinin is a perfect match (1701/1701) to 22 PF11 specimens from geographies including Sao Paulo, Finland, Italy and 18 specimens along the US Eastern Seaboard.  The HA 296H polymorphism deepens in Japan with this deposit being only the second in Japan, the eighth in Asia and the fifty-first in the world.  The sub-clades bearing 296H do not appear to have become dominant in any single geography, but have, nonetheless, continued alongside the dominant strains.  As of this moment, the Intra-Segment Exclusivity between 296H and 206T continues within ΣPF11 though 206T is widely circulating proximally to this specimen.

Cross-segment linking is suggested with all HA:296H specimens sharing the NA combination of 106I, 248D, 275H, 286S (for those 44 with NA on record).  No specimen bearing HA:296H is on record as TamiFlu Resistant or as carrying the NA:286G from Seasonal Influenza (H1N1/H3N2) or H5N1.

This specimen also demonstrates the strong pairing between 296H and the 2E originally found in 1918 sequences and now several PF11 HA segments.

We would be very happy to report that sub-clades are coalescing and stability is occurring within ΣPF11, but the data does not support such a view.  Even casual observation of the sparsely available sequences shows ongoing genetic acquisition leading to Antigenic Diversity and widening sub-clades.  Reversion and flux appear.

Tracking of these non-random linkings would certainly be assisted by a more robust database of recent sequences.

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