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 (pH1N1_υ), but several, including one Swedish fatality of a 10 year old male, have crossover polymorphisms previously described in the pH1N1_υ 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 pH1N1_υ 144E & 144T) and equality to the pH1N1_υ 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)

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