France Highlights Polymorphic Fluctuation in 83 Day Series

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
2011-07-18

On 2011-07-06, the Institut Pasteur published 18 pH1N1 sequences at GISAID (9 HA segments and 9 matching NA segments) with no clinical outcome noted, but with multiple manifestations of drug resistance markers related to TamiFlu Resistance.  These apparently related sequences span 83 days from 2009-11-20 to 2010-02-11 with a residual effect of significant genetic re-seeding being measured on 2010-01-28.

Due to publication as a set from this institute, the GeneWurx analysis will process the data as a time series panel without emphasis on individual host.  Alternate gain and loss of specific polymorphisms are highlighted for evaluation.  Dysmorphic behaviour is observed.

Sixteen of the segments are notated as being sampled from a 24 year old male with two segment fragments, matching HA and NA dated 2009-12-01, being notated as sampled from a 14 year old male.  Perhaps the two males are related or an administrative error resulted in a typographical error from 24 to 14 on the age?  Genetic homology is indicated with the HA segment fragment in question (noted 14M) matching all positions of sequences from the 24 year old both earlier and later in the 83 day progression.  The NA segment noted as sampled from the 14M accumulates 3 changes variously found on the remaining 24M samples, including NA 275Y marking TamiFlu drug resistance.

The Receptor Binding Site is revised on 2 sequences at HA 190N, a rare change to pH1N1.  The small set of pH1N1 190N-bearing sequences share no HA or NA homology to these 2 French sequences, suggesting an ultimate origin influencer from a non-human source and an ability of 190N to appear on new backgrounds given a particular set of circumstances.  TamiFlu resistance is genetically found on 2 sequences that are identical on the HA, outside of a variation at the potential HA domaining amino range of 418 to 421.

Significant variation is demonstrated across the time progression in the HA and NA segments that may be characterised as an ebb and flow of polymorphisms with the final products indicating a substantial net gain with selective aggregation from previous samples.  The initial HA shows 3 silent changes while the final HA in the panel shows 7 polymorphisms (4 amino and the same 3 silent); however, the progression is not linear on gain:

2009_11_20 (0 Amino, 3 Silent) syn169I, syn175E, syn541C.
2009_11_26 (1 Amino, 3 Silent) Gain 418L mix wt.
2009_12_01 (1 Amino, 3 Silent) Fragment with 418L mix wt.
2009_12_09 (1 Amino, 3 Silent) Drop 418L. Gain 421L.
2009_12_15 (1 Amino, 3 Silent) Drop 421L. Gain 418L mix wt.
2010_01_04 (4 Amino, 3 Silent) Gain 100N mix wt, 324I, 421L.
2010_01_28 (4 Amino, 3 Silent) Drop 100N, 421L. Gain 227G mix wt, 377K.
2010_01_28 (10 Amino, 5 Silent) Drop 227G, 377K.
. . . . . . . . . . . . . . . . . . . . . . Gain 100N mix wt, syn131S mix wt,
. . . . . . . . . . . . . . . . . . . . . . . . . . 190N mix wt, 219K mix wt, 241G mix wt,
. . . . . . . . . . . . . . . . . . . . . . . . . . 324A mix wt, 324I mix wt, 324T mix wt,
. . . . . . . . . . . . . . . . . . . . . . . . . . 421L, 447K, syn520Y mix wt.
2010_02_11 (4 Amino, 3 Silent) Drop 100N, syn131S, 190N, 219K, 241G,
. . . . . . . . . . . . . . . . . . . . . . . . . . 324I, 324T, 418L, syn520Y.

The initial NA shows 1 silent change while the final NA in the panel shows 4 polymorphisms (2 Amino and 2 silent); however, the progression is not linear on gain:

2009_11_20 (0 Amino, 1 Silent) syn422F.
2009_11_26 (1 Amino, 1 Silent) Gain 223R mix wt.
2009_12_01 (2 Amino, 1 Silent) Fragment. Gain 275Y TamiFlu Resistance.
2009_12_09 (1 Amino, 1 Silent) Drop 223R.
2009_12_15 (1 Amino, 1 Silent) Drop 275Y. Gain 223R mix wt.
2010_01_04 (1 Amino, 1 Silent) Persist at 223R mix wt, syn422F.
2010_01_28 (0 Amino, 1 Silent) Drop 223R.
2010_01_28 (4 Amino, 2 Silent) Gain 153T mix wt, 223R,
. . . . . . . . . . . . . . . . . . . . . . . . . syn328P mix wt, 329D mix wt, 331Q mix wt.
2010_02_11 (2 Amino, 2 Silent) Drop 153T, 331Q.

Sequences

. . . . FranceParis1158_24M_2010_02_11 (
. . . . . . . . GISAID HA EPI324964
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . syn169I (ATc),
. . . . . . . . syn175E (GAg),
. . . . . . . . 190N mix wt,
. . . . . . . . 324A mix wt,
. . . . . . . . 421L,
. . . . . . . . 447K mix wt,
. . . . . . . . syn541C (TGt))

. . . . FranceParis1158_24M_2010_02_11 (
. . . . . . . . GISAID NA EPI324963
. . . . . . . . 4 Polymorphisms (2 Amino and 2 Silent)
. . . . . . . . 223R,
. . . . . . . . syn328P (CCc),
. . . . . . . . 329D,
. . . . . . . . syn422F (TTt))

. . . . FranceParis1159_24M_2010_01_28 (
. . . . . . . . GISAID HA EPI324967
. . . . . . . . 15 Polymorphisms (10 Amino and 5 Silent)
. . . . . . . . 100N mix wt,
. . . . . . . . syn131S (TCa) mix wt,
. . . . . . . . syn169I (ATc),
. . . . . . . . syn175E (GAg),
. . . . . . . . 190N mix wt,
. . . . . . . . 219K mix wt,
. . . . . . . . 241G mix wt,
. . . . . . . . 324A mix wt,
. . . . . . . . 324I mix wt,
. . . . . . . . 324T mix wt,
. . . . . . . . 418L mix wt,
. . . . . . . . 421L,
. . . . . . . . 447K mix wt,
. . . . . . . . syn520Y (TAc) mix wt,
. . . . . . . . syn541C (TGt))

. . . . FranceParis1159_24M_2010_01_28 (
. . . . . . . . GISAID NA EPI324966
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 153T mix wt [swAsia2006],
. . . . . . . . 223R,
. . . . . . . . syn328P (CCc) mix wt,
. . . . . . . . 329D mix wt,
. . . . . . . . 331Q mix wt,
. . . . . . . . syn422F (TTt))

. . . . FranceParis1157_24M_2010_01_28 (
. . . . . . . . GISAID HA EPI324961
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . syn169I (ATc),
. . . . . . . . syn175E (GAg),
. . . . . . . . 227G mix wt,
. . . . . . . . 324I,
. . . . . . . . 377K,
. . . . . . . . 418L mix wt,
. . . . . . . . syn541C (TGt))

. . . . FranceParis1157_24M_2010_01_28 (
. . . . . . . . GISAID NA EPI324960
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . syn422F (TTt))

. . . . FranceParis1156_24M_2010_01_04 (
. . . . . . . . GISAID HA EPI324958
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 100N mix wt,
. . . . . . . . syn169I (ATc),
. . . . . . . . syn175E (GAg),
. . . . . . . . 324I,
. . . . . . . . 418L mix wt,
. . . . . . . . 421L,
. . . . . . . . syn541C (TGt))

. . . . FranceParis1156_24M_2010_01_04 (
. . . . . . . . GISAID NA EPI324957
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 223R mix wt,
. . . . . . . . syn422F (TTt))
. . . . FranceParis7973_24M_2009_12_15 (
. . . . . . . . GISAID HA EPI324946
. . . . . . . . 4 Polymorphisms (1 Amino and 3 Silent)
. . . . . . . . syn169I (ATc),
. . . . . . . . syn175E (GAg),
. . . . . . . . 418L mix wt,
. . . . . . . . syn541C (TGt))

. . . . FranceParis7973_24M_2009_12_15 (
. . . . . . . . GISAID NA EPI324945
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 223R mix wt,
. . . . . . . . syn422F (TTt))

. . . . FranceParis7974_24M_2009_12_09_TmX (
. . . . . . . . GISAID HA EPI324949
. . . . . . . . 4 Polymorphisms (1 Amino and 3 Silent)
. . . . . . . . syn169I (ATc),
. . . . . . . . syn175E (GAg),
. . . . . . . . 421L,
. . . . . . . . syn541C (TGt))

. . . . FranceParis7974_24M_2009_12_09_TmX (
. . . . . . . . GISAID NA EPI324948
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 275Y,
. . . . . . . . syn422F (TTt))

. . . . FranceParis7154_14M_2009_12_01_TmX (
. . . . . . . . GISAID HA EPI324943
. . . . . . . . 4 Polymorphisms (1 Amino and 3 Silent)
. . . . . . . . syn169I (ATc),
. . . . . . . . syn175E (GAg),
. . . . . . . . 418L mix wt,
. . . . . . . . syn541C (TGt),
. . . . . . . . HA Truncated after aa548)

. . . . FranceParis7154_14M_2009_12_01_TmX (
. . . . . . . . GISAID NA EPI324942
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . 223R mix wt,
. . . . . . . . 275Y mix wt,
. . . . . . . . syn422F (TTt),
. . . . . . . . NA Truncated after aa469)

. . . . FranceParis7975_24M_2009_11_26 (
. . . . . . . . GISAID HA EPI324952
. . . . . . . . 4 Polymorphisms (1 Amino and 3 Silent)
. . . . . . . . syn169I (ATc),
. . . . . . . . syn175E (GAg),
. . . . . . . . 418L mix wt,
. . . . . . . . syn541C (TGt))

. . . . FranceParis7975_24M_2009_11_26 (
. . . . . . . . GISAID NA EPI324951
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 223R mix wt,
. . . . . . . . syn422F (TTt))

. . . . FranceParis7976_24M_2009_11_20 (
. . . . . . . . GISAID HA EPI324955
. . . . . . . . 3 Polymorphisms (0 Amino and 3 Silent)
. . . . . . . . syn169I (ATc),
. . . . . . . . syn175E (GAg),
. . . . . . . . syn541C (TGt))

. . . . FranceParis7976_24M_2009_11_20 (
. . . . . . . . GISAID NA EPI324954
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . syn422F (TTt))

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