Greece Deposits pH1N1 Clade5 from 2011 Hospitalisation with Novel Diversity

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
2011-11-05

On 2011-10-31, the Institut Pasteur Hellenique deposited one human pH1N1 HA fragment sequence at GISAID of 216 amino acids (aa35 to aa220), documenting roughly 38% of a full pH1N1 Hemagglutinin segment.  GreeceAthens7033_75M_2011_02_22_s was sampled from a 75 year old male, hospital inpatient.  This hypermorphic fragment patterns onto Clade5: 208K_219V, a highly zoonotic, recently emergent series with a sequence count that has quickly accumulated to triple digits.

Two dispersed polymorphisms, each novel to pH1N1.Clade5, appear on this Greek sequence.  HA 77R, a novel Clade5 revision, is rare to the human pandemic and is emergent on Clade2 (3 instances).  Those 3 Clade2, HA 77R-bearing HA segment sequences are hypermorphic (accounting for 48 total HA changes); however, no HA cross-over onto this Greek sequence occurs from the full superset of polymorphisms with HA 77R.  HA 169T, also novel to Clade5, is rare to the human pandemic and is found once on Clade2, the numerically dominant series for human pH1N1.

Avian H13 serotypes share significant homology with pH1N1.Clade5 and this Greek sequence.  Given the serology background of the more recently discovered Hemagglutinin forms above H12 (~30 years for H13 to ~6 years for H16), question arise concerning cross-serotype compatibility.  Returning to the archives after these recent discoveries, investigators repeatedly found that H16 samples from the past had been mis-typed on first inspection to various Hemagglutinin forms (H1, H7, H13) due to cross-reactive serology on various inhibition panels.  Serotypes known to infect humans, including H1 and H7, featured in those earlier mistaken categorisations. 

Precise discernment of the exact relationship between the current human pandemic H1N1 and the more recently discovered Hemagglutinin forms (H13 to H16) merits evaluation due to the significant H13 homology with the heavily zoonotic and rapidly emergent pH1N1.Clade5 and the High CFR pH1N1.Clade1.Upsilon.

Sequence

. . . . GreeceAthens7033_75M_2011_02_22_s (
. . . . . . . . Clade5: 208K_219V
. . . . . . . . GISAID HA EPI340964
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . HA Truncated before aa35,
. . . . . . . . syn47L (CTg) [H1N1 Avian],
. . . . . . . . 77R (AGa) [Rare to Human pH1N1 (11 Total / 5 Asia)],
. . . . . . . . . . . . . . . [Novel to pH1N1.Clade5],
. . . . . . . . . . . . . . . [Emergent pH1N1.Clade2 (3)],
. . . . . . . . . . . . . . . [H9N2 Avian and Human wt
. . . . . . . . . . . . . . . . . . . . with pH1N1υ polymorphisms],
. . . . . . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . . . . [WSN_1933, WSZ_1933],
. . . . . . . . 100N [H5N1 Egypt Avian 2009-2010
. . . . . . . . . . . . . . . . . with syn40H, syn55L, 192I, 196K],
. . . . . . . . . . . . [H5N1 Egypt Avian 2008 with syn40H, syn55L],
. . . . . . . . . . . . [H5N2 Italy Avian 2005-2007],
. . . . . . . . . . . . [H7N3, H7N7, H9N2],
. . . . . . . . . . . . [H13N2 Mammal],
. . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . syn102E (GAa) [H5N1 wt],
. . . . . . . . . . . . . . . . . . . [H9N2 Early Human wt, Human 2008],
. . . . . . . . . . . . . . . . . . . [H9N2 Avian wt],
. . . . . . . . . . . . . . . . . . . [H10N7 Avian 2008
. . . . . . . . . . . . . . . . . . . . . . with 87N, 100N, syn102E,
. . . . . . . . . . . . . . . . . . . . . . . . 156E, 157E, 163T, 165N,
. . . . . . . . . . . . . . . . . . . . . . . . syn177L, 188T, syn221P, syn207S, syn213F,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, 230I, 233H, 237I, syn239P,
. . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn356H,
. . . . . . . . . . . . . . . . . . . . . . . . syn390N, syn391T],
. . . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 169T [Rare to Human pH1N1 (6 Total / 3 Asia)],
. . . . . . . . . . . [Novel to pH1N1.Clade5],
. . . . . . . . . . . [Singular to pH1N1.Clade2],
. . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . . . . [H1N1 swine],
. . . . . . . . syn170N (AAc) [H5N1 Egypt Human 2009],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . . . [H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . . . with 225G & 252L],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K (AaA) [pH1N1 Canine 2009],
. . . . . . . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . . . . . . . . . [H3N2 Avian 2006, 2009],
. . . . . . . . 219V (gTA) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . [H13N2, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . syn221P (CCt) [H3N2 Avian
. . . . . . . . . . . . . . . . . . . . . with 157S, 159S, syn287G],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human and Avian (tCt)],
. . . . . . . . . . . . . . . . . . [H5N1 Nigeria Avian (tCt)],
. . . . . . . . . . . . . . . . . . [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],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal],
. . . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . HA Truncated after aa250)

Supporting Sequences

HA 169T

. . . . Montana03_2011_02_02 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI310031
. . . . . . . . 8 Polymorphisms (6 Amino and 2 Silent)
. . . . . . . . 100N,
. . . . . . . . 169T,
. . . . . . . . 188T,
. . . . . . . . 213S,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))

. . . . Lebanon09L_29_2009_11_05 (
. . . . . . . . GISAID HA EPI320624
. . . . . . . . 4 Polymorphisms (4 Amino and 0 Silent)
. . . . . . . . #1T,
. . . . . . . . 169T,
. . . . . . . . 225E,
. . . . . . . . 300S,
. . . . . . . . HA Truncated after aa355)

. . . . ShanxiChengquSWL547_2009_10_19 (
. . . . . . . . GISAID HA EPI256314
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . 57N,
. . . . . . . . 131P,
. . . . . . . . 169T,
. . . . . . . . syn238E (GAa))

. . . . TianjinTangguSWL1110_2009_10_13 (
. . . . . . . . GISAID HA EPI256126
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . 169T,
. . . . . . . . 206S,
. . . . . . . . 447K,
. . . . . . . . syn455Q (CAa))

. . . . BeijingHuairouSWL1805_2009_10_01 (
. . . . . . . . GISAID HA EPI256274
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . 169T,
. . . . . . . . 206S,
. . . . . . . . 447K,
. . . . . . . . syn455Q (CAa))

. . . . Russia01_MA_2009 (
. . . . . . . . GISAID HA EPI297205
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . 169T,
. . . . . . . . 208K,
. . . . . . . . syn359E (GAa))

HA 77R on Clade2

. . . . OzBrisbane500_2011_06_22 (
. . . . . . . . GISAID HA EPI333109
. . . . . . . . 18 Polymorphisms (8 Amino and 10 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn33V (GTc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 77R,
. . . . . . . . syn99I (ATt),
. . . . . . . . syn115E (GAg),
. . . . . . . . 146G,
. . . . . . . . 171G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn338G (GGc),
. . . . . . . . syn346G (GGa),
. . . . . . . . 377K,
. . . . . . . . syn413K (AAg),
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn508L (tTG),
. . . . . . . . 523A,
. . . . . . . . HA Truncated after aa552)

. . . . OzNewcastle1_2011_04_11 (
. . . . . . . . GISAID HA EPI331558
. . . . . . . . 21 Polymorphisms (9 Amino and 12 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn33V (GTc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 77R,
. . . . . . . . syn99I (ATt),
. . . . . . . . syn115E (GAg),
. . . . . . . . 146G,
. . . . . . . . 157Q mix wt,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn338G (GGc),
. . . . . . . . syn346G (GGa),
. . . . . . . . 377K,
. . . . . . . . syn413K (AAg),
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn508L (tTG),
. . . . . . . . 523A,
. . . . . . . . syn538F (TTt),
. . . . . . . . syn549R (AGg),
. . . . . . . . 550S,
. . . . . . . . HA Truncated after aa550)

. . . . JapanHiroshimaC2_2011_01_05 (
. . . . . . . . GISAID HA EPI305466
. . . . . . . . 9 Polymorphisms (6 Amino and 3 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 71D,
. . . . . . . . 77R,
. . . . . . . . 102G mix wt,
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa348)

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