Morocco Reports Hypermorphism on pH1N1 HA and NA Fragments

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
2011-11-03

On 2011-10-25, the Institute Pasteur of Morocco deposited a group of human pH1N1 sequences at GenBank and GISAID.  HA segments include 14 fragments.  The NA segment is represented with 15 fragments, 7 that are related to a deposited HA fragment.  All sequences are marked geographically as Casablanca.  The sample dates span 2010-12-20 to 2011-04-01 with no specification of treatment protocol, clinical progression or clinical outcome.

Hypermorphic behaviour is found on 71% of the sequences that have both HA and NA segments, notwithstanding the fact that both segments are fragments across this deposit.  These 5 hypermorphic representatives are on two separate lineages. Additionally, the NA fragment of  MoroccoCasablanca69_11F_2011_01_26  [EPI340865] demonstrates significant, rare zoonotic homology to Avian H1N1, H5N1 and Avian H9N2.

Multi-clade hypermorphism in a single geography and within a contemporaneous time span merits careful evaluation.

Zoonoses of Polymorphisms

The mammal and avian database of Influenza A H13 covering all Neuraminidase forms comprises only 93 sequences, yet shares homology to pH1N1 human polymorphisms on Clade1.Upsilon as well as rare and novel pH1N1 human polymorphisms on Clade2, Clade4 and Clade5 sequences in this Moroccan deposit.  Several of these shared polymorphisms, e.g. markers for Clade5 (HA 219V and HA 252L), are previously uncharacterised as to potential Ultimate Origin.  The identification of multi-clade hypermorphism in this geography with wide homology to a single candidate animal reservoir (A/H13) solidifies the clear requirement for higher levels of avian surveillance.

Cladistics

10 - Clade2: 188T
01 - Clade4: 128D [EPI340861]
03 - Clade5: 208K_219V [EPI340881], [EPI340860], [EPI340876]

HA   84 Polymorphisms Averaging ~6.0 per Segment Fragment
NA 118 Polymorphisms Averaging ~7.9 per Segment Fragment

HA and NA 202 Total Polymorphisms Averaging ~13.9 per Sequence (Fragments)

Diversity

HA Superset – 36 Distinct Values
NA Superset - 47 Distinct Values

Two Receptor Binding Site items of interest are syn221P and 224K.  No indication is found of revisions at aa225, aa226 or aa230.  The Clade5 sequence bearing HA syn221P is contemporary in timing and homology to a small group of European Clade5 sequences.  A hypermorphic, Clade2 Moroccan sequence bears HA 224K, a polymorphism previously found in pH1N1 swine Clade5, suggesting a potential cross-clade transfer or compatibility.  The HA 224K may signal tissue tropism issues, having been documented on a lethal, neurotropic experimental strain (WSN_1933).

• [EPI340860] MoroccoCasablanca91_15mM_2011_02_02 – HA syn221P
• [EPI340866] MoroccoCasablanca69_11F_2011_01_26    – HA 224K

Hypermorphic Behaviour

04 HA Fragments >= 7 polymorphisms (29%)
13 NA Segments  >= 7 polymorphisms (87%)

Combined Polymorphic Count >= 15
5 of 7 Sequences with HA and NA Fragments (71%)
Total (HA / NA)

• 16 (HA 09 / NA 07): [EPI340881] MoroccoCasablanca117_10m_2011_02_15
• 16 (HA 07 / NA 09): [EPI340860] MoroccoCasablanca91_15mM_2011_02_02
• 16 (HA 05 / NA 11): [EPI340866] MoroccoCasablanca69_11F_2011_01_26
• 16 (HA 09 / NA 07): [EPI340876] MoroccoCasablanca23_3F_2011_01_13
• 15 (HA 09 / NA 07): [EPI340868] MoroccoCasablanca63_47F_2011_01_20

Sequences

. . . . MoroccoCasablanca124_5M_2011_04_01 (
. . . . . . . . GISAID NA EPI340879
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . NA Truncated before aa36,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca211_15M_2010_12_20 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340885
. . . . . . . . 4 Polymorphisms (2 Amino and 2 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa354)

. . . . MoroccoCasablanca117_10m_2011_02_15 (
. . . . . . . . Clade5: 208K_219V crossing with
. . . . . . . . . . . Clade2: 188T Defining Marker syn338G
. . . . . . . . GISAID HA EPI340881
. . . . . . . . 9 Polymorphisms (4 Amino and 5 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian],
. . . . . . . . syn82I (ATc) [H5N2 Avian],
. . . . . . . . syn93C (TGc) [H5N1 Avian Domestic & Wild],
. . . . . . . . . . . . . . . . . [H9N2 Avian Emergent 2009],
. . . . . . . . . . . . . . . . . [H13N2 Mammal],
. . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . 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],
. . . . . . . . 141Q (CAa) [H13 Avian (gAa, gga)],
. . . . . . . . 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],
. . . . . . . . syn338G (GGc) [Clade2, Rare to Clade5],
. . . . . . . . HA Truncated after aa342)

. . . . MoroccoCasablanca117_10m_2011_02_15 (
. . . . . . . . GISAID NA EPI340880
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . NA Truncated before aa33,
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H1N1 Avian (Cat)],
. . . . . . . . . . . . . . . . . .[H9N2 Avian (Ctt)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 299A,
. . . . . . . . 454V [Rare to pH1N1 (1)],
. . . . . . . . NA Truncated after aa454)

. . . . MoroccoCasablanca110_3F_2011_02_09 (
. . . . . . . . GISAID NA EPI340882
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa38,
. . . . . . . . 38V [H9N2 Avian],
. . . . . . . . syn60T (ACc) [H1N1 Avian Farm],
. . . . . . . . 81A [H1N1 Avian],
. . . . . . . . syn138A (GCt) [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . 192N [H9N2 Avian (cac)],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca107_xF_2011_02_09 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340883
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#4,
. . . . . . . . 100N,
. . . . . . . . 173R,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa341)

. . . . MoroccoCasablanca103_5M_2011_02_07 (
. . . . . . . . GISAID HA EPI340884
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#7,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 324D [Novel to pH1N1],
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa350)

. . . . MoroccoCasablanca92_52F_2011_02_02 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340858
. . . . . . . . 8 Polymorphisms (6 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#3,
. . . . . . . . 22E [Novel to pH1N1],
. . . . . . . . 34T [Novel to pH1N1 2011],
. . . . . . . . 47Q [Novel to pH1N1],
. . . . . . . . 60V [H1N1 Avian],
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa341)

. . . . MoroccoCasablanca91_15mM_2011_02_02 (
. . . . . . . . Clade5: 208K_219V
. . . . . . . . GISAID HA EPI340860
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa82,
. . . . . . . . 100F [Novel to pH1N1],
. . . . . . . . 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],
. . . . . . . . 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
. . . . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive Upsilon polymorphisms],
. . . . . . . . 252L (tTG) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . HA Truncated after aa352)

. . . . MoroccoCasablanca91_15mM_2011_02_02 (
. . . . . . . . GISAID NA EPI340859
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa36,
. . . . . . . . 69V [H1N1 Avian],
. . . . . . . . 81A [H1N1 Avian],
. . . . . . . . 106M,
. . . . . . . . syn138A (GCt) [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn395G (GGg),
. . . . . . . . NA Truncated after aa452)

. . . . MoroccoCasablanca76_13M_2011_01_26 (
. . . . . . . . Clade4: 128D
. . . . . . . . GISAID HA EPI340861
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa13,
. . . . . . . . 28P [Novel to pH1N1.Clade4],
. . . . . . . . . . . [pH1N1 with Avian Influence (3)],
. . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . with 188T, syn210S, 225G & 252L],
. . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . with 188T, syn210S, 225G & 252L],
. . . . . . . . syn60I (ATc) [H9N2 Human and Avian Emergent],
. . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6,
. . . . . . . . . . . . . . . . . . . H13N8, H13N9 Avian (tTc)
. . . . . . . . . . . . . . . . . . . . . . with 28P, 188T, syn210S],
. . . . . . . . . . . . . . . . [1918],
. . . . . . . . 128D,
. . . . . . . . syn210S (AGt) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . . . with 28P, 188T, 225G & 252L],
. . . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . . . with 28P, 188T, 225G & 252L],
. . . . . . . . 298V [H3N2 Avian, Canine, Feline & Mink],
. . . . . . . . . . . [H3N8],
. . . . . . . . . . . [H5 Avian, H6 Avian],
. . . . . . . . . . . [H9N2],
. . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . HA Truncated after aa341)

. . . . MoroccoCasablanca73_43F_2011_01_26 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340863
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa0,
. . . . . . . . 11L [Novel to pH1N1],
. . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . with 28P, 188T, syn210S, 225G & 252L],
. . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . with 28P, 188T, syn210S, 225G & 252L],
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 259T [Recently Novel to pH1N1υ],
. . . . . . . . . . . . [H9N2 Avian and Human (att)
. . . . . . . . . . . . . . . . with syn40H],
. . . . . . . . . . . . [Not Found in H1N1 Swine with 124N],
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa338)

. . . . MoroccoCasablanca73_43F_2011_01_26 (
. . . . . . . . GISAID NA EPI340862
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . NA Truncated before aa44,
. . . . . . . . syn126P (CCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn293R (AGa) [H1N1 Avian Farm],
. . . . . . . . . . . . . . . . . . . [H5N1 Avian],
. . . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca69_11F_2011_01_26 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340866
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#5,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 224K [swine pH1N1.Clade5]
. . . . . . . . . . . . [WSN_1933],
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa339)

. . . . MoroccoCasablanca69_11F_2011_01_26 (
. . . . . . . . GISAID NA EPI340865
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . NA Truncated before aa35,
. . . . . . . . 70N [H1N1 Avian],
. . . . . . . . syn137G (GGa) [H1N1 Avian],
. . . . . . . . syn215T (ACa) [H1N1 Avian],
. . . . . . . . 235D [H9N2 Avian],
. . . . . . . . syn240T (ACc) [H1N1 Avian],
. . . . . . . . 241I [H1N1 Avian],
. . . . . . . . 260R [H1N1 Avian],
. . . . . . . . 369K [H1N1 Avian],
. . . . . . . . syn377P (CCa) [H1N1 Avian],
. . . . . . . . syn386N (AAt) [H1N1 Environment],
. . . . . . . . syn416D (GAc) [H5N1 wt],
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca63_47F_2011_01_20 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340868
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa3,
. . . . . . . . syn90N (AAc) [Rare to pH1N1],
. . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa339)

. . . . MoroccoCasablanca63_47F_2011_01_20 (
. . . . . . . . GISAID NA EPI340867
. . . . . . . . 10 Polymorphisms (6 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa20,
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 262N,
. . . . . . . . 263V [H1N1 Avian],
. . . . . . . . . . . . [H5N1 wt],
. . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . 269I [H5N1 (tTa)],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . 420C,
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca60_43F_2011_01_20 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340869
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa#3,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn205G (GGa),
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa338)

. . . . MoroccoCasablanca54_23F_2011_01_20 (
. . . . . . . . GISAID NA EPI340870
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa17,
. . . . . . . . 54L,
. . . . . . . . 81A [H1N1 Avian],
. . . . . . . . syn138A (GCt) [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn395G (GGg),
. . . . . . . . NA Truncated after aa454)

. . . . MoroccoCasablanca52_25F_2011_01_20 (
. . . . . . . . GISAID NA EPI340871
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . NA Truncated before aa19,
. . . . . . . . 43R,
. . . . . . . . 44T,
. . . . . . . . 45L,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa452)

. . . . MoroccoCasablanca28_10M_2011_01_13 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340873
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#6,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 340M,
. . . . . . . . HA Truncated after aa340)

. . . . MoroccoCasablanca28_10M_2011_01_13 (
. . . . . . . . GISAID NA EPI340872
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . NA Truncated before aa21,
. . . . . . . . 54V [H1N1 Avian],
. . . . . . . . . . [H9N2 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . 454V [Rare to pH1N1 (1)],
. . . . . . . . NA Truncated after aa454)

. . . . MoroccoCasablanca26_24M_2011_01_13 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340874
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . syn136T (ACt),
. . . . . . . . 176I,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa353)

. . . . MoroccoCasablanca23_3F_2011_01_13 (
. . . . . . . . Clade5: 208K_219V
. . . . . . . . GISAID HA EPI340876
. . . . . . . . 9 Polymorphisms (4 Amino and 5 Silent)
. . . . . . . . HA Truncated before aa#7,
. . . . . . . . syn36L (tTA) [H5N1 Avian (tTg)],
. . . . . . . . syn47L (CTg) [H1N1 Avian],
. . . . . . . . 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],
. . . . . . . . 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],
. . . . . . . . syn184H (CAc) [Early pH1N1 Highly Zoonotic]
. . . . . . . . . . . . . . . . . . [swine pH1N1.Clade5],
. . . . . . . . . . . . . . . . . . [H2N3, H3N8],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Fatality 2010],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2009],
. . . . . . . . . . . . . . . . . . [H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal],
. . . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 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],
. . . . . . . . 252L (tTG) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . HA Truncated after aa335)

. . . . MoroccoCasablanca23_3F_2011_01_13 (
. . . . . . . . GISAID NA EPI340875
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa39,
. . . . . . . . syn87G (GGg) [H9N2 Avian (aag)],
. . . . . . . . syn138A (GCt) [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 242V [H9N2 Avian],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . NA Truncated after aa455)

. . . . MoroccoCasablanca17_12F_2011_01_07 (
. . . . . . . . GISAID NA EPI340877
. . . . . . . . 8 Polymorphisms (3 Amino and 5 Silent)
. . . . . . . . NA Truncated before aa35,
. . . . . . . . syn176S (TCg) [H1N1 Avian],
. . . . . . . . 213K,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn338V (GTg) [H1N1 Avian],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca15_35F_2011_01_06 (
. . . . . . . . GISAID NA EPI340878
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa35,
. . . . . . . . syn126P (CCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 263V [H1N1 Avian],
. . . . . . . . . . . . [H5N1 wt],
. . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . 269I [H5N1 (tTa)],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa454)

. . . . MoroccoCasablanca07_23F_2011_01_05 (
. . . . . . . . GISAID NA EPI340864
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . NA Truncated before aa34,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . 419S,
. . . . . . . . 420A,
. . . . . . . . 428I,
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca210_2010_12_20 (
. . . . . . . . GISAID NA EPI340886
. . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa17,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn273N (AAc) [H1N1 Avian],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa457)

Supporting Sequences

. . . . NewYork7420_2010_01_02 (
. . . . . . . . GenBank HA CY065067
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . 35I [H5N1 Egypt Human 2009-2010],
. . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . syn80S (TCt) [H5N1 Egypt Human 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H6N1, H7N3, H9N2, H11],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with #1T, 8V, 22I, syn31H,
. . . . . . . . . . . . . . . . . . . . . . . . syn40H, syn42G, 72L,
. . . . . . . . . . . . . . . . . . . . . . . . syn81Y, syn82I, 87N
. . . . . . . . . . . . . . . . . . . . . . . . syn118E, 144E, 158E,
. . . . . . . . . . . . . . . . . . . . . . . . 189T, 200T, 218S, 218V,
. . . . . . . . . . . . . . . . . . . . . . . . 237I, syn287G, syn346G,
. . . . . . . . . . . . . . . . . . . . . . . . 453K, 502K, 523A, 523I],
. . . . . . . . syn159N (AAc) [H3N8 Avian & Equine],
. . . . . . . . . . . . . . . [H9N2],
. . . . . . . . syn184H (CAc) [Early pH1N1 Highly Zoonotic]
. . . . . . . . . . . . . . . . . . [swine pH1N1.Clade5],
. . . . . . . . . . . . . . . . . . [H2N3, H3N8],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Fatality 2010],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2009],
. . . . . . . . . . . . . . . . . . [H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . 236I [H3N8],
. . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . [H5N1 Egypt Avian 2008-2010],
. . . . . . . . . . . . [H6, H7N7, H9N2 2009, H11],
. . . . . . . . syn413K (AAg) [H1N1 Avian, H2, H5N1, H9N2],
. . . . . . . . syn441H (CAt) [H1N1 Avian, H2, H5N1, H6, H9N2, H11])

. . . . NewYork7425_2009_12_20 (
. . . . . . . . GenBank HA CY065091
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . 35I [H5N1 Egypt Human 2009-2010],
. . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . syn113S (TCg) [1918],
. . . . . . . . syn159N (AAc) [H3N8 Avian & Equine],
. . . . . . . . . . . . . . . [H9N2],
. . . . . . . . syn184H (CAc) [Early pH1N1 Highly Zoonotic]
. . . . . . . . . . . . . . . . . . [swine pH1N1.Clade5],
. . . . . . . . . . . . . . . . . . [H2N3, H3N8],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Fatality 2010],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2009],
. . . . . . . . . . . . . . . . . . [H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . 236I [H3N8],
. . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . [H5N1 Egypt Avian 2008-2010],
. . . . . . . . . . . . [H6, H7N7, H9N2 2009, H11],
. . . . . . . . syn413K (AAg) [H1N1 Avian, H2, H5N1, H9N2],
. . . . . . . . syn441H (CAt) [H1N1 Avian, H2, H5N1, H6, H9N2, H11])

. . . . Texas43242018_2009_07_24 (
. . . . . . . . GenBank HA CY051823
. . . . . . . . 5 Polymorphisms (0 Amino and 5 Silent)
. . . . . . . . syn184H (CAc) [Early pH1N1 Highly Zoonotic]
. . . . . . . . . . . . . . . . . . [swine pH1N1.Clade5],
. . . . . . . . . . . . . . . . . . [H2N3, H3N8],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Fatality 2010],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2009],
. . . . . . . . . . . . . . . . . . [H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . syn239P (CCt) [H1N1 Avian],
. . . . . . . . syn297N (AAc) [H3N2 Asia Avian 1975-1977 with 159S, 453K],
. . . . . . . . . . . . . . . . . . [H3N8 Avian],
. . . . . . . . . . . . . . . . . . [H5N1],
. . . . . . . . . . . . . . . . . . [H9N2 Human, Avian, Equine and Seal wt],
. . . . . . . . . . . . . . . . . . [H9N2 Avian 2009],
. . . . . . . . syn453R (AGg) [H1N1 Avian],
. . . . . . . . syn525S (AGc) [H1N1 Avian])

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Japan Demonstrates 2011 pH1N1 Multi-Segment Hypermorphism

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
2011-10-27

On 2011-10-19, the Japanese Influenza Collaborative Study Group based at Niigata University released a group of human pH1N1 sequences at GenBank and GISAID including 46 HA fragments and 46 full NA segments.  The sample dates span 2011-01-04 to 2011-03-08.  Seven geographic areas of Japan are covered with no specification of subject age, subject gender, treatment protocol, clinical progression or clinical outcome notated.

Cladistics

Clade2: 188T is represented on 44 sequences crossing all geographic divisions and Clade3: 186P is found once each in Niigata and Osaka.  Although cladding is clear, perhaps due to publication bias, overall diversity is high. That diversity and the sheer polymorphic count demonstrate the instability of human pH1N1 as the reservoir continues to undergo revision.

HA 320 Polymorphisms Averaging ~7.0 per Segment Fragment
NA 352 Polymorphisms Averaging ~7.6 per Segment

HA and NA 672 Total Polymorphisms Averaging ~14.6 per Sequence (HA Fragments)

Diversity

The HA superset producing 77 distinct values includes 4 polymorphisms (syn31H, syn42G, 189T, syn287G) that appear on the High CFR Clade1.Upsilon revision set.  Polymorphic sets shared across pH1N1 clades suggest cross-clade compatibility.  H5N1 involvement is notated on JapanOsaka10K362_2011_02_15, [EPI340541].  Notably absent in this deposit are Receptor Binding Site changes at HA aa225.  The NA superset produces 85 distinct values.  No mixed peaks (ambiguity) are found on any segment though significant zoonoses are represented.

Hypermorphic Behaviour

14 HA Fragments >= 8 polymorphisms (30%)
20 NA Segments >= 8 polymorphisms (43%)

Combined Polymorphic Count >= 17
Total (HA / NA)

• 21 (HA 11 / NA 10): [EPI340579] JapanHokkaido10H054_2011_02_07
• 21 (HA 11 / NA 10): [EPI340574] JapanHyogo10K055_2011_01_24
• 19 (HA 11 / NA 08): [EPI340549] JapanNiigata10F257_2011_02_03
• 18 (HA 10 / NA 08): [EPI340551] JapanNiigata10F202_2011_01_31
• 18 (HA 10 / NA 08): [EPI340552] JapanNiigata10F117_2011_01_25
• 18 (HA 07 / NA 11): [EPI340548] JapanNiigata10F306_2011_02_05
• 18 (HA 11 / NA 07): [EPI340543] JapanOsaka10K346_2011_02_07
• 17 (HA 07 / NA 10): [EPI340555] JapanNagasaki10N103_2011_02_10
• 17 (HA 08 / NA 09): [EPI340561] JapanKyoto10K385_2011_02_22
• 17 (HA 09 / NA 08): [EPI340568] JapanHyogo10K308_2011_02_14

TamiFlu Resistance

Two TamiFlu Resistant sequences (NA 275Y) each feature on Clade2: 188T backgrounds having significant HA and NA homology with Avian H1N1.

• [EPI340570] JapanHyogo10K291_2011_02_07_TmX
• [EPI340564] JapanKyoto10K124_2011_01_28_TmX

Sequences

. . . . JapanNiigata10F557_2011_03_08 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340547
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . HA Truncated after aa329)

. . . . JapanNiigata10F557_2011_03_08 (
. . . . . . . . GISAID NA EPI340662
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn304V (GTa),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . JapanKyoto10K393_2011_02_25 (
. . . . . . . . GISAID HA EPI340560
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . syn#6L (tTG),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn53L (TTa),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . HA Truncated after aa329)

. . . . JapanKyoto10K393_2011_02_25 (
. . . . . . . . GISAID NA EPI340675
. . . . . . . . 7 Polymorphisms (5 Amino and 2 Silent)
. . . . . . . . 44S,
. . . . . . . . 62I,
. . . . . . . . syn237S (TCa),
. . . . . . . . 240I,
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . JapanKyoto10K385_2011_02_22 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340561
. . . . . . . . 8 Polymorphisms (3 Amino and 5 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn130D (GAt),
. . . . . . . . 146G,
. . . . . . . . syn162P (CCg),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn321L (TTa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanKyoto10K385_2011_02_22 (
. . . . . . . . GISAID NA EPI340676
. . . . . . . . 9 Polymorphisms (6 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . 62L,
. . . . . . . . 127S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn427I (ATa),
. . . . . . . . 431S)

. . . . JapanOsaka10K366_2011_02_21 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340539
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . syn#12K (AAa),
. . . . . . . . #6M,
. . . . . . . . syn34N (AAt),
. . . . . . . . syn122K (AAa),
. . . . . . . . 146G,
. . . . . . . . 156T,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . HA Truncated after aa329)

. . . . JapanOsaka10K366_2011_02_21 (
. . . . . . . . GISAID NA EPI340654
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . 13A,
. . . . . . . . 44S,
. . . . . . . . syn64Q (CAa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn378N (AAt))

. . . . JapanNagasaki10N088_2011_02_19 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340556
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . #6M,
. . . . . . . . syn34N (AAt),
. . . . . . . . syn122K (AAa),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn258F (TTt),
. . . . . . . . HA Truncated after aa329)

. . . . JapanNagasaki10N088_2011_02_19 (
. . . . . . . . GISAID NA EPI340671
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . 86T,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn378N (AAt))

. . . . JapanOsaka10K363_2011_02_16 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340540
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . 288S,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanOsaka10K363_2011_02_16 (
. . . . . . . . GISAID NA EPI340655
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . syn157T (ACa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanOsaka10K362_2011_02_15 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340541
. . . . . . . . 7 Polymorphisms (5 Amino and 2 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . 33I,
. . . . . . . . syn34N (AAt),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . 305E [H5N1 wt],
. . . . . . . . HA Truncated after aa329)

. . . . JapanOsaka10K362_2011_02_15 (
. . . . . . . . GISAID NA EPI340656
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . 44S,
. . . . . . . . syn121F (TTt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn304V (GTa),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . JapanHyogo10K308_2011_02_14 (
. . . . . . . . Clade2: 188T crossed with 189T from Clade1
. . . . . . . . GISAID HA EPI340568
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . syn10Y (TAc) [H1N1 Avian],
. . . . . . . . syn34N (AAt) [H1N1 Avian],
. . . . . . . . syn98F (TTt) [H1N1 Avian],
. . . . . . . . syn122K (AAa) [H1N1 Avian],
. . . . . . . . 146G,
. . . . . . . . 166T,
. . . . . . . . 188T [H1N1 Avian],
. . . . . . . . 189T [pH1N1 Clade1.Upsilon],
. . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 200T [H1N1 Avian],
. . . . . . . . HA Truncated after aa329)

. . . . JapanHyogo10K308_2011_02_14 (
. . . . . . . . GISAID NA EPI340683
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . 44S,
. . . . . . . . syn104N (AAt) [H1N1 Avian],
. . . . . . . . syn240T [H1N1 Avian],
. . . . . . . . 241I [H1N1 Avian],
. . . . . . . . syn287E (GAg) [H1N1 Avian],
. . . . . . . . 369K [H1N1 Avian],
. . . . . . . . syn377P (CCa) [H1N1 Avian],
. . . . . . . . 451N [H3N8 Equine, Canine, Swine (aAa)])

. . . . JapanHokkaido10H073_2011_02_14 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340578
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn223V (GTa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanHokkaido10H073_2011_02_14 (
. . . . . . . . GISAID NA EPI340693
. . . . . . . . 10 Polymorphisms (7 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . 140V,
. . . . . . . . 224F,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn304V (GTa),
. . . . . . . . 309D,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 392N)

. . . . JapanOsaka10K358_2011_02_12 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340542
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . HA Truncated after aa329)

. . . . JapanOsaka10K358_2011_02_12 (
. . . . . . . . GISAID NA EPI340657
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn304V (GTa),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . JapanHyogo10K302_2011_02_12 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340569
. . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
. . . . . . . . syn#12K (AAa),
. . . . . . . . syn31H (CAt) [pH1N1 Clade1.Upsilon],
. . . . . . . . syn34N (AAt),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanHyogo10K302_2011_02_12 (
. . . . . . . . GISAID NA EPI340684
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn301R (CGg),
. . . . . . . . syn326P (CCg),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M,
. . . . . . . . 454D)

. . . . JapanNagasaki10N103_2011_02_10 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340555
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . syn42G (GGa) [pH1N1 Clade1.Upsilon],
. . . . . . . . syn50V (GTt),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn296Q (CAa),
. . . . . . . . 297D,
. . . . . . . . HA Truncated after aa329)

. . . . JapanNagasaki10N103_2011_02_10 (
. . . . . . . . GISAID NA EPI340670
. . . . . . . . 10 Polymorphisms (7 Amino and 3 Silent)
. . . . . . . . syn42N (AAc),
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 257K,
. . . . . . . . 351Y,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M,
. . . . . . . . 416G)

. . . . JapanNagasaki10N073_2011_02_09 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340557
. . . . . . . . 4 Polymorphisms (2 Amino and 2 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanNagasaki10N073_2011_02_09 (
. . . . . . . . GISAID NA EPI340672
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . syn28N (AAt),
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanOsaka10K346_2011_02_07 (
. . . . . . . . Clade3: 186P
. . . . . . . . GISAID HA EPI340543
. . . . . . . . 11 Polymorphisms (6 Amino and 5 Silent)
. . . . . . . . syn#12K (AAa),
. . . . . . . . 41T,
. . . . . . . . 135A,
. . . . . . . . 137T,
. . . . . . . . 144S,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg) [pH1N1 Clade1.Upsilon],
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V,
. . . . . . . . HA Truncated after aa329)

. . . . JapanOsaka10K346_2011_02_07 (
. . . . . . . . GISAID NA EPI340658
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 46T,
. . . . . . . . syn126P (CCt),
. . . . . . . . syn187G (GGt),
. . . . . . . . 313R,
. . . . . . . . 394I,
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)

. . . . JapanHyogo10K291_2011_02_07_TmX (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340570
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . 17G,
. . . . . . . . syn34N (AAt) [H1N1 Avian],
. . . . . . . . 188T [H1N1 Avian],
. . . . . . . . 200T [H1N1 Avian],
. . . . . . . . syn296Q [H1N1 Avian],
. . . . . . . . HA Truncated after aa329)

. . . . JapanHyogo10K291_2011_02_07_TmX (
. . . . . . . . GISAID NA EPI340685
. . . . . . . . 9 Polymorphisms (6 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . 47G [H1N1 Avian Farm],
. . . . . . . . syn126P (CCt),
. . . . . . . . syn240T [H1N1 Avian],
. . . . . . . . 241I [H1N1 Avian],
. . . . . . . . 275Y,
. . . . . . . . 369K [H1N1 Avian],
. . . . . . . . syn377P (CCa) [H1N1 Avian],
. . . . . . . . 415M [H1N1 Avian Farm])

. . . . JapanHokkaido10H054_2011_02_07 (
. . . . . . . . Clade 2: 188T
. . . . . . . . GISAID HA EPI340579
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn122K (AAa),
. . . . . . . . 146G,
. . . . . . . . syn174K (AAg),
. . . . . . . . syn177L (CTt),
. . . . . . . . syn185P (CCg),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . 218E,
. . . . . . . . 253A,
. . . . . . . . HA Truncated after aa329)

. . . . JapanHokkaido10H054_2011_02_07 (
. . . . . . . . GISAID NA EPI340694
. . . . . . . . 10 Polymorphisms (5 Amino and 5 Silent)
. . . . . . . . 44S,
. . . . . . . . syn152R (AGa),
. . . . . . . . syn234V (GTg),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn392D (GAc),
. . . . . . . . 396T,
. . . . . . . . 469N)

. . . . JapanNiigata10F306_2011_02_05 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340548
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . syn22V (GTc),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn42G (GGa) [pH1N1 Clade1.Upsilon],
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn296Q (CAa),
. . . . . . . . 297D,
. . . . . . . . HA Truncated after aa329)

. . . . JapanNiigata10F306_2011_02_05 (
. . . . . . . . GISAID NA EPI340663
. . . . . . . . 11 Polymorphisms (8 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . 58Y,
. . . . . . . . 67I,
. . . . . . . . 86V,
. . . . . . . . syn224L (cTG),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . 371Y,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanOsaka10K340_2011_02_04 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340544
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn239P (CCa),
. . . . . . . . syn259A (GCg),
. . . . . . . . 264T,
. . . . . . . . HA Truncated after aa329)

. . . . JapanOsaka10K340_2011_02_04 (
. . . . . . . . GISAID NA EPI340659
. . . . . . . . 9 Polymorphisms (6 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . 62I,
. . . . . . . . 77V,
. . . . . . . . 90T,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn366S (AGc),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . JapanHyogo10K283_2011_02_04 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340571
. . . . . . . . 7 Polymorphisms (5 Amino and 2 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . 205E,
. . . . . . . . 276Q,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanHyogo10K283_2011_02_04 (
. . . . . . . . GISAID NA EPI340686
. . . . . . . . 9 Polymorphisms (6 Amino and 3 Silent)
. . . . . . . . 38F,
. . . . . . . . 44S,
. . . . . . . . 143N,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn251A (GCt),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanKyoto10K250_2011_02_04 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340562
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . #6M,
. . . . . . . . syn34N (AAt),
. . . . . . . . syn122K (AAa),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . HA Truncated after aa329)

. . . . JapanKyoto10K250_2011_02_04 (
. . . . . . . . GISAID NA EPI340677
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn378N (AAt),
. . . . . . . . 415M)

. . . . JapanNiigata10F257_2011_02_03 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340549
. . . . . . . . 11 Polymorphisms (4 Amino and 7 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn50V (GTg),
. . . . . . . . 89N,
. . . . . . . . syn98F (TTt),
. . . . . . . . syn122K (AAa),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn214K (AAa),
. . . . . . . . syn293L (CTt),
. . . . . . . . HA Truncated after aa329)

. . . . JapanNiigata10F257_2011_02_03 (
. . . . . . . . GISAID NA EPI340664
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 13I,
. . . . . . . . 44S,
. . . . . . . . syn104N (AAt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 451N)

. . . . JapanKyoto10K243_2011_02_02 (
. . . . . . . . GISAID HA EPI340563
. . . . . . . . 10 Polymorphisms (3 Amino and 7 Silent)
. . . . . . . . syn33V (GTc),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn42G (GGa) [pH1N1 Clade1.Upsilon],
. . . . . . . . syn96G (GGg),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn205G (GGa),
. . . . . . . . syn214K (AAa),
. . . . . . . . syn296Q (CAa),
. . . . . . . . 297D,
. . . . . . . . HA Truncated after aa329)

. . . . JapanKyoto10K243_2011_02_02 (
. . . . . . . . GISAID NA EPI340678
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanNiigata10F228_2011_02_01 (
. . . . . . . . GISAID HA EPI340550
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 146G,
. . . . . . . . syn162P (CCt),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . HA Truncated after aa329)

. . . . JapanNiigata10F228_2011_02_01 (
. . . . . . . . GISAID NA EPI340665
. . . . . . . . 9 Polymorphisms (3 Amino and 6 Silent)
. . . . . . . . syn12S (TCa),
. . . . . . . . 44S,
. . . . . . . . syn148T (ACt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn304V (GTa),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn378N (AAt))

. . . . JapanGunma10G021_2011_02_01 (
. . . . . . . . GISAID HA EPI340582
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn211K (AAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanGunma10G021_2011_02_01 (
. . . . . . . . GISAID NA EPI340697
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn304V (GTa),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . JapanOsaka10K332_2011_01_31 (
. . . . . . . . GISAID HA EPI340545
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . syn42G (GGa) [pH1N1 Clade1.Upsilon],
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanOsaka10K332_2011_01_31 (
. . . . . . . . GISAID NA EPI340660
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn382G (GGa),
. . . . . . . . 415M)

. . . . JapanHyogo10K275_2011_01_31 (
. . . . . . . . GISAID HA EPI340572
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . 205E,
. . . . . . . . HA Truncated after aa329)

. . . . JapanHyogo10K275_2011_01_31 (
. . . . . . . . GISAID NA EPI340687
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . 143N,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn304V (GTa),
. . . . . . . . 364N,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . JapanNiigata10F202_2011_01_31 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340551
. . . . . . . . 10 Polymorphisms (3 Amino and 7 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn50V (GTg),
. . . . . . . . syn98F (TTt),
. . . . . . . . syn122K (AAa),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn214K (AAa),
. . . . . . . . syn293L (CTt),
. . . . . . . . HA Truncated after aa329)

. . . . JapanNiigata10F202_2011_01_31 (
. . . . . . . . GISAID NA EPI340666
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . 44S,
. . . . . . . . syn104N (AAt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn243T (ACa),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 451N)

. . . . JapanHokkaido10H041_2011_01_31 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340580
. . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanHokkaido10H041_2011_01_31 (
. . . . . . . . GISAID NA EPI340695
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . 100H,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn252S (TCg),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanKyoto10K124_2011_01_28_TmX (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340564
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . syn34N (AAt) [H1N1 Avian],
. . . . . . . . syn37E (GAg) [H1N1 Avian Farm],
. . . . . . . . 146G [H3N8 Avian],
. . . . . . . . . . . . [H3N2 Avian, Canine, Feline
. . . . . . . . . . . . . . . . with 165N, 190E, 225G, 230I, 238K, 275I],
. . . . . . . . 188T [H1N1 Avian],
. . . . . . . . 200T [H1N1 Avian],
. . . . . . . . syn259A (GCg) [H1N1 Avian],
. . . . . . . . HA Truncated after aa329)

. . . . JapanKyoto10K124_2011_01_28_TmX (
. . . . . . . . GISAID NA EPI340679
. . . . . . . . 9 Polymorphisms (6 Amino and 3 Silent)
. . . . . . . . 43H [H1N1 Avian],
. . . . . . . . 44S [H1N1 Avian],
. . . . . . . . syn240T [H1N1 Avian],
. . . . . . . . 241I [H1N1 Avian],
. . . . . . . . 275Y,
. . . . . . . . syn366S (AGc) [H1N1 Avian],
. . . . . . . . 369K [H1N1 Avian],
. . . . . . . . syn377P (CCa) [H1N1 Avian],
. . . . . . . . 381A)

. . . . JapanNiigata10F117_2011_01_25 (
. . . . . . . . Clade3: 186P
. . . . . . . . GISAID HA EPI340552
. . . . . . . . 10 Polymorphisms (5 Amino and 5 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . 137T,
. . . . . . . . 144S,
. . . . . . . . 146G,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg) [pH1N1 Clade1.Upsilon],
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V,
. . . . . . . . HA Truncated after aa329)

. . . . JapanNiigata10F117_2011_01_25 (
. . . . . . . . GISAID NA EPI340667
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 32V,
. . . . . . . . 46T,
. . . . . . . . syn126P (CCt),
. . . . . . . . syn187G (GGt),
. . . . . . . . 313R,
. . . . . . . . 394I,
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)

. . . . JapanHyogo10K061_2011_01_25 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340573
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . 166N,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . 288S,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanHyogo10K061_2011_01_25 (
. . . . . . . . GISAID NA EPI340688
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . syn157T (ACa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanGunma10G013_2011_01_25 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340583
. . . . . . . . 4 Polymorphisms (2 Amino and 2 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanGunma10G013_2011_01_25 (
. . . . . . . . GISAID NA EPI340698
. . . . . . . . 7 Polymorphisms (5 Amino and 2 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 288V,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanOsaka10K323_2011_01_24 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340546
. . . . . . . . 8 Polymorphisms (3 Amino and 5 Silent)
. . . . . . . . syn#8V (GTg),
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn130D (GAt),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn280T (ACc),
. . . . . . . . HA Truncated after aa329)

. . . . JapanOsaka10K323_2011_01_24 (
. . . . . . . . GISAID NA EPI340661
. . . . . . . . 10 Polymorphisms (5 Amino and 5 Silent)
. . . . . . . . 44S,
. . . . . . . . 127S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn315G (GGg),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn382G (GGa),
. . . . . . . . 432T,
. . . . . . . . syn436I (ATt))

. . . . JapanHyogo10K055_2011_01_24 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340574
. . . . . . . . 11 Polymorphisms (6 Amino and 5 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn33V (GTc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 86F,
. . . . . . . . syn99I (ATt),
. . . . . . . . syn116R (AGa),
. . . . . . . . 123A,
. . . . . . . . 146G,
. . . . . . . . 169V,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . HA Truncated after aa329)

. . . . JapanHyogo10K055_2011_01_24 (
. . . . . . . . GISAID NA EPI340689
. . . . . . . . 10 Polymorphisms (3 Amino and 7 Silent)
. . . . . . . . 44S,
. . . . . . . . syn139L (cTG),
. . . . . . . . syn158L (tTA),
. . . . . . . . syn183A (GCc),
. . . . . . . . syn195I (ATc),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn246P (CCg),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))

. . . . JapanGunma10G004_2011_01_21 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340584
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . syn42G (GGa) [pH1N1 Clade1.Upsilon],
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanGunma10G004_2011_01_21 (
. . . . . . . . GISAID NA EPI340699
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanHyogo10K045_2011_01_20 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340575
. . . . . . . . 8 Polymorphisms (3 Amino and 5 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . syn42G (GGa) [pH1N1 Clade1.Upsilon],
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn205G (GGa),
. . . . . . . . syn214K (AAa),
. . . . . . . . syn296Q (CAa),
. . . . . . . . 297D,
. . . . . . . . HA Truncated after aa329)

. . . . JapanHyogo10K045_2011_01_20 (
. . . . . . . . GISAID NA EPI340690
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanKyoto10K025_2011_01_18 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340565
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . syn#4Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanKyoto10K025_2011_01_18 (
. . . . . . . . GISAID NA EPI340680
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanNiigata10F025_2011_01_18 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340553
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . syn42G (GGa) [pH1N1 Clade1.Upsilon],
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn296Q (CAa),
. . . . . . . . 297D,
. . . . . . . . HA Truncated after aa329)

. . . . JapanNiigata10F025_2011_01_18 (
. . . . . . . . GISAID NA EPI340668
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanHyogo10K037_2011_01_17 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340576
. . . . . . . . 9 Polymorphisms (3 Amino and 6 Silent)
. . . . . . . . syn33V (GTc),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn42G (GGa),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn205G (GGa),
. . . . . . . . syn214K (AAa),
. . . . . . . . syn296Q (CAa),
. . . . . . . . 297D,
. . . . . . . . HA Truncated after aa329)

. . . . JapanHyogo10K037_2011_01_17 (
. . . . . . . . GISAID NA EPI340691
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M,
. . . . . . . . syn460G (GGc))

. . . . JapanHokkaido10H031_2011_01_17 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340581
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . #1E,
. . . . . . . . syn34N (AAt),
. . . . . . . . syn42G (GGa),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanHokkaido10H031_2011_01_17 (
. . . . . . . . GISAID NA EPI340696
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn330D (GAc),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanNiigata10F012_2011_01_17 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340554
. . . . . . . . 9 Polymorphisms (4 Amino and 5 Silent)
. . . . . . . . #6M,
. . . . . . . . syn34N (AAt),
. . . . . . . . syn122K (AAa),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn240G (GGg),
. . . . . . . . syn258F (TTt),
. . . . . . . . syn299H (CAc),
. . . . . . . . HA Truncated after aa329)

. . . . JapanNiigata10F012_2011_01_17 (
. . . . . . . . GISAID NA EPI340669
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . 44S,
. . . . . . . . syn210G (GGa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn378N (AAt))

. . . . JapanKyoto10K012_2011_01_15 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340566
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn212K (AAa),
. . . . . . . . 289M,
. . . . . . . . HA Truncated after aa329)

. . . . JapanKyoto10K012_2011_01_15 (
. . . . . . . . GISAID NA EPI340681
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 44S,
. . . . . . . . 46V,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn449N (AAt))

. . . . JapanHyogo10K029_2011_01_13 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340577
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . syn42G (GGa),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanHyogo10K029_2011_01_13 (
. . . . . . . . GISAID NA EPI340692
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanKyoto10K002_2011_01_12 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340567
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . syn31H (CAt) [pH1N1 Clade1.Upsilon],
. . . . . . . . syn34N (AAt),
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanKyoto10K002_2011_01_12 (
. . . . . . . . GISAID NA EPI340682
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanNagasaki10N010_2011_01_11 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340558
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . 143E,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanNagasaki10N010_2011_01_11 (
. . . . . . . . GISAID NA EPI340673
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . syn28N (AAt),
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

. . . . JapanNagasaki10N005_2011_01_04 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340559
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . syn36L (tTA),
. . . . . . . . 163M,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . 238K,
. . . . . . . . syn296Q (CAa),
. . . . . . . . HA Truncated after aa329)

. . . . JapanNagasaki10N005_2011_01_04 (
. . . . . . . . GISAID NA EPI340674
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . syn28N (AAt),
. . . . . . . . 44S,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . 415M)

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100% Case Fatality Rate on pH1N1 Clade2 Lineage (HA 142V & NA syn204A)

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
2011-10-25

HA 142V appears on 22 pH1N1 human sequences geographically spanning 5 countries covering 16 cases documented from 2009-07-20 (Italy) to 2011-02-04 (Russia).  Researchers produced multiple sequences for 5 cases.  These 22 sequences delineate on the last day of 2010 from low polymorphic count genetics onto highly polymorphic Clade2: 188T backgrounds.  The 9 most current HA 142V sequences share 6 HA revisions and 5 NA revisions demonstrating capable transmission.

At a minimum, 7 of those sequences represent fatalities.  These fatality sequences were generated from 2 independent labs.  The subjects were geographically dispersed (Nizhnii Novgorod and Vladimir: >100 miles distant).  Non-fatality sequences (2) with HA 142V on similar Clade2 backgrounds are on file in a similar region of the world (Tula, Russia and Slovenia).  Of 9 Clade2 sequences with HA 142V, 7 are noted as fatal (78% Case Fatality Rate).  5 of those 9 Clade2 sequences carry Receptor Binding Site revisions between HA aa225 and aa230, including 225G, 225N and 230I.  Although the amino-level Ultimate Origin investigation for Valine at aa142 continues, many H5N1 sequences demonstrate the 2nd Base Codon donation potential (atg, ctt, ctg, ttg) to create the pH1N1 142V (GtT).

An examination of the Neuraminidase segments provides additional sectioning to the fatalities.  The NA segments are hyper-morphic and zoonotic.  Each Clade2 fatality with HA 142V carries NA syn204A. The 2 Clade2 non-fatality HA 142V-bearing sequences do not demonstrate the NA syn204A.  All NA syn204A (GCa) pH1N1 sequences (7) are in cross-segment combination with HA 142V on a very common Clade2: 188T background. 

Potential animal progenitors are found on 18 sequences in Avian and Mink hosts across several serotypes (H4N4, H5N4, H7N1, H8N4, H10N4).  The databases do not yet appear to demonstrate NA syn204A (GCa) on an Avian H1N1 sequence.  Future Avian H1N1 deposits may very well demonstrate that this value has crossed to human pH1N1 via an Avian H1N1 bridge (intermediate) from one of the noted H4N4, H5N4, H7N1, H8N4 or H10N4 serotypes.

7 human fatalities on 7 cases across 2 cities and 2 labs each bearing the rare HA 142V and the rarer NA syn204A merit attention as a potential “flashfire” candidate due to the 100% Case Fatality Rate (CFR) of this transmissible combination found on the most dominant pH1N1 Clade.  Furthermore, this group of sequences demonstrates a superset of revisions (HA and NA) with significant homology to the Avian H1N1 pool.  Each pH1N1 chimera strain that is in mid-stride between host species, that is “confused”, holds the potential for variant clinical symptoms and outcomes.   Early detection of "flashfire" strains (High CFR) via increased surveillance is essential to public health planning.

Case Fatality Rates for HA 142V

44% CFR Overall (7 of 16)
78% CFR on Clade2 (2010-12-31 to 2011-02-14) (7 of 9)
78% CFR in Northern Hemisphere from 2010-12-31 to 2011-02-14 (7 of 9)
100% CFR with NA syn204A (7 of 7)

Hemagglutinin Statistics for HA 142V

Total HA: 123 Polymorphisms (2 to 14) on 22 HA Segments
. . . . . . . . with 30 Distinct Values
. . . . . . . . Averaging ~5.6 Polymorphisms per HA Segment

Total HA Clade2: 88 Polymorphisms (8 to 14) on 9 Segments
. . . . . . . . . . . . with 24 Distinct Values
. . . . . . . . . . . . Averaging ~9.8 Polymorphisms per Clade2 HA Segment

HA 142V is not found as a singleton polymorphism, even on short fragments. 100% of HA 142V-bearing pH1N1 human sequences (22) also carry either HA 188T (9), syn194L (12) or 225E (1, Origin pH1N1).

Neuraminidase Statistics for HA 142V

Total NA: 94 Polymorphisms (1 to 12) on 20 Segments
. . . . . . . . with 20 Distinct Values
. . . . . . . . Averaging ~4.7 Polymorphisms per HA Segment

Total NA Clade2: 81 Polymorphisms (7 to 12) on 9 Segments
. . . . . . . . . . . . with 19 Distinct Values
. . . . . . . . . . . . Averaging ~9.0 Polymorphisms per Clade2 NA Segment

100% of the available related NA segments (20) carries NA syn416D.

Clade2 Shared Polymorphisms

HA Background: 100N, 142V, 188T, syn338G, 377K, 454N (6 common)
NA Background: [76S (8), 77E (1)], syn240T, 241I, 369K, syn377P, syn416D (5 common)

Sequences

. . . . RussiaTulaCRIE_KEE_2011_02_04 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI335282
. . . . . . . . 10 Polymorphisms (5 Amino and 5 Silent)
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . syn154L (CTg) [Rare to pH1N1 Human (3 Total: 2 on Clade2)]
. . . . . . . . . . . . . . . . . . [H1N1 Avian Farm
. . . . . . . . . . . . . . . . . . . . . with #1T, syn202V
. . . . . . . . . . . . . . . . . . . . . . . . & extensive pH1N1υ polymorphisms],
. . . . . . . . . . . . . . . . . . [H1N1 swine],
. . . . . . . . . . . . . . . . . . [H7N7 Avian and Human (tcg)],
. . . . . . . . . . . . . . . . . . [H9N2 Avian 2009 & Human 2009
. . . . . . . . . . . . . . . . . . . . . with pH1N1υ polymorphisms],
. . . . . . . . . . . . . . . . . . [S9, M9, S7],
. . . . . . . . . . . . . . . . . . [WSN1933, WSZ1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . 188T,
. . . . . . . . syn202V (GTc) [H1N1 Avian Farm
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . . . . . . . . . . . [H6N1 Avian],
. . . . . . . . . . . . . . . . . . [S9],
. . . . . . . . . . . . . . . . . . [H1N1 Human 1943, 1946, 1951],
. . . . . . . . . . . . . . . . . . [WSN1933, WSZ1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn542S (TCc))

. . . . RussiaTulaCRIE_KEE_2011_02_04 (
. . . . . . . . GISAID NA EPI335288
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . RussiaVladimirIIV35_T_27M_2011_01_31_f (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI324794
. . . . . . . . 14 Polymorphisms (10 Amino and 4 Silent)
. . . . . . . . 1T [42 pH1N1,
. . . . . . . . . . . . . only 9 from 2010-2011 Season (NH)],
. . . . . . . . . . [H1N1 Avian Farm
. . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . . . [H6N1 Avian (agc)]
. . . . . . . . . . [H7N7 Avian & Human Fatality],
. . . . . . . . . . [H9N2 Avian & Human (agc, agt, atc)],
. . . . . . . . . . [Netherlands2457b_2009_11_07_xL
. . . . . . . . . . . . . . . . . . with 225N,
. . . . . . . . . . IndiaHyderabad51_2009_05
. . . . . . . . . . . . . . . . . . with syn144A],
. . . . . . . . . . [H1N1 swine],
. . . . . . . . . . [S9, M9, S7],
. . . . . . . . . . [1976],
. . . . . . . . . . [WSN1933, WSZ1933],
. . . . . . . . . . [1918],
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . 157Q mix wt,
. . . . . . . . 188T,
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn515Q (CAa) [H5N1 Avian & Human wt],
. . . . . . . . syn527L (TTa) [H5N1 Avian])

. . . . RussiaVladimirIIV35_T_27M_2011_01_31_f (
. . . . . . . . GISAID NA EPI324795
. . . . . . . . 9 Polymorphisms (3 Amino and 6 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . syn204A (GCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn291V (GTa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . RussiaNizhniiNovgorodCRIE_BLM_L_2011_01_26_TmX_f (
. . . . . . . . Clade2: 188T with 230I
. . . . . . . . GISAID HA EPI339320
. . . . . . . . 10 Polymorphisms (7 Amino and 3 Silent)
. . . . . . . . 77N [Recently Novel to Clade1.Upsilon],
. . . . . . . . . . . . [Emergent on pH1N1 Clade 1 (189T)
. . . . . . . . . . . . . . . . with 124N, 233H, 275A],
. . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . with syn42G, 159T,
. . . . . . . . . . . . . . . . . . . . 188T, 189T, syn346G, 453K],
. . . . . . . . . . . . [Rare to H1N1 US Swine with 124N (6)],
. . . . . . . . 100N,
. . . . . . . . 142V [H5N1 Avian (atg, ctg)],
. . . . . . . . 188T,
. . . . . . . . 230I (ATt) [H9N2 Avian & Human wt],
. . . . . . . . . . . . [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],
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt) [H2 2009],
. . . . . . . . . . . . . . . . . . [H3N8 Canine 2007, Equine 2009, Swine],
. . . . . . . . . . . . . . . . . . [H5N1 wt],
. . . . . . . . . . . . . . . . . . [H5N2 Avian],
. . . . . . . . . . . . . . . . . . [H9N2 2009],
. . . . . . . . . . . . . . . . . . [H1N1 Avian 2010],
. . . . . . . . . . . . . . . . . . [H1N1 swine 2010],
. . . . . . . . syn542S (TCc) [H2, H5, H9N2],
. . . . . . . . . . . . . . . . . . [H1N1 Avian Farm
. . . . . . . . . . . . . . . . . . . . . with pH1N1υ polymorphisms])

. . . . RussiaNizhniiNovgorodCRIE_BLM_L_2011_01_26_TmX_f (
. . . . . . . . GISAID NA EPI339322
. . . . . . . . 10 Polymorphisms (4 Amino and 6 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . syn111K (AAa) [H1N1 Avian Farm],
. . . . . . . . syn204A (GCa),
. . . . . . . . syn240T (ACc) [H1N1 Avian Farm],
. . . . . . . . 241I [H1N1 Avian Farm],
. . . . . . . . 275Y mix wt,
. . . . . . . . 369K [H1N1 Avian
. . . . . . . . . . . . . . . . with syn111K, syn240T, 241I],
. . . . . . . . syn377P (CCa) [H5N1 Avian],
. . . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with 241I],
. . . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . exclusive of syn240T (ACc)],
. . . . . . . . syn416D (GAc) [H5N1 Avian Emergent 2011],
. . . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with syn51Q, syn240T, 241I],
. . . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with syn111K, syn377P])

. . . . RussiaNizhniiNovgorodCRIE_LAV_L_2011_01_24_f (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI335268
. . . . . . . . 9 Polymorphisms (6 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . 188T,
. . . . . . . . 225G,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn542S (TCc))

. . . . RussiaNizhniiNovgorodCRIE_LAV_L_2011_01_24_f (
. . . . . . . . GISAID NA EPI335295
. . . . . . . . 8 Polymorphisms (3 Amino and 5 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . syn204A (GCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . RussiaNizhniiNovgorodCRIE_OAV_L_2011_01_24_f (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI335280
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn542S (TCc))

. . . . RussiaNizhniiNovgorodCRIE_OAV_L_2011_01_24_f (
. . . . . . . . GISAID NA EPI335294
. . . . . . . . 8 Polymorphisms (3 Amino and 5 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . syn204A (GCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . RussiaNizhniiNovgorodCRIE_UBA_L_2011_01_23_f (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI335274
. . . . . . . . 12 Polymorphisms (9 Amino and 3 Silent)
. . . . . . . . 50I,
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . 188T,
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn542S (TCc))

. . . . RussiaNizhniiNovgorodCRIE_UBA_L_2011_01_23_f (
. . . . . . . . GISAID NA EPI335301
. . . . . . . . 12 Polymorphisms (5 Amino and 7 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 149F,
. . . . . . . . syn152R (AGa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . syn204A (GCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn291V (GTa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 305A,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . Slovenia414_75F_2011_01_19 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI331063
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N,
. . . . . . . . syn467C (TGt) mix wt [H1N1 Avian Farm])

. . . . Slovenia414_75F_2011_01_19 (
. . . . . . . . GISAID NA EPI331064
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . 77E [H1N1 Avian],
. . . . . . . . syn162P (CCc) [H1N1 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 242I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . RussiaNizhniiNovgorodCRIE_PAV_L_2011_01_10_f (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI339341
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn542S (TCc))

. . . . RussiaNizhniiNovgorodCRIE_PAV_L_2011_01_10_f (
. . . . . . . . GISAID NA EPI339342
. . . . . . . . 10 Polymorphisms (5 Amino and 5 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 115L,
. . . . . . . . syn204A (GCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 322L [H1N1 Avian with syn240T, 241I],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . RussiaNizhniiNovgorodCRIE_NGV_L_2010_12_31_f (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI339312
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . 142V,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn542S (TCc))

. . . . RussiaNizhniiNovgorodCRIE_NGV_L_2010_12_31_f (
. . . . . . . . GISAID NA EPI339314
. . . . . . . . 9 Polymorphisms (4 Amino and 5 Silent)
. . . . . . . . syn51Q (CAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 76S [H1N1 Avian
. . . . . . . . . . . . . . with syn240T, 241I],
. . . . . . . . 115L,
. . . . . . . . syn204A (GCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))

. . . . Moldova93_CS_2010_01_05 (
. . . . . . . . GISAID HA EPI278150
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . 324I (aTC) [H1N1 Avian],
. . . . . . . . . . . . . . [H3N2 Avian with 159S],
. . . . . . . . . . . . . . [H3N2 Canine with syn287G],
. . . . . . . . . . . . . . [H3N8 Avian Emergent],
. . . . . . . . . . . . . . [H6 Avian],
. . . . . . . . . . . . . . [S8],
. . . . . . . . HA Truncated after aa396)

. . . . Moldova93_CS_2010_01_05 (
. . . . . . . . GISAID NA EPI278149
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . syn416D (GAc))

. . . . KazakhstanTaraz01_2009_12 (
. . . . . . . . GISAID HA EPI235349
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 4Y,
. . . . . . . . syn111V (GTa) [H1N1 Avian],
. . . . . . . . . . . . . . . . [H9N2 Human (Gca)],
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . 225G,
. . . . . . . . 324I (aTC) [H1N1 Avian],
. . . . . . . . . . . . . . [H3N2 Avian with 159S],
. . . . . . . . . . . . . . [H3N2 Canine with syn287G],
. . . . . . . . . . . . . . [H3N8 Avian Emergent],
. . . . . . . . . . . . . . [H6 Avian],
. . . . . . . . . . . . . . [S8])

. . . . KazakhstanAlmaty373_9M_2009_11_28 (
. . . . . . . . GISAID HA EPI277103
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)

. . . . KazakhstanAlmaty373M_9M_2009_11_28 (
. . . . . . . . GISAID NA EPI277104
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa193,
. . . . . . . . syn416D (GAc))

. . . . KazakhstanAlmaty373CX_9M_2009_11_28 (
. . . . . . . . GISAID HA EPI271067
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)

. . . . KazakhstanAlmaty373CX_9M_2009_11_28 (
. . . . . . . . GISAID NA EPI271068
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa193,
. . . . . . . . syn416D (GAc))

. . . . KazakhstanAlmaty352M_9M_2009_11_23 (
. . . . . . . . GISAID HA EPI277101
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)

. . . . KazakhstanAlmaty352M_9M_2009_11_23 (
. . . . . . . . GISAID NA EPI277102
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa184,
. . . . . . . . syn416D (GAc))

. . . . KazakhstanAlmaty352CX_9M_2009_11_23 (
. . . . . . . . GISAID HA EPI271065
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)

. . . . KazakhstanAlmaty352CX_9M_2009_11_23 (
. . . . . . . . GISAID NA EPI271066
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa184,
. . . . . . . . syn416D (GAc))

. . . . KazakhstanAlmaty347M_18M_2009_11_19 (
. . . . . . . . GISAID HA EPI277098
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . 124I [H1N1 Avian],
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)

. . . . KazakhstanAlmaty347M_18M_2009_11_19 (
. . . . . . . . GISAID NA EPI277099
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa184,
. . . . . . . . syn416D (GAc))

. . . . KazakhstanAlmaty347_NP_18M_2009_11_19 (
. . . . . . . . GISAID HA EPI277097
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . 124I [H1N1 Avian],
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)

. . . . KazakhstanAlmaty347_NP_18M_2009_11_19 (
. . . . . . . . GISAID NA EPI277100
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa184,
. . . . . . . . syn416D (GAc))

. . . . KazakhstanAlmaty347CX_18M_2009_11_19 (
. . . . . . . . GISAID HA EPI271063
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . 124I [H1N1 Avian],
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)

. . . . KazakhstanAlmaty347CX_18M_2009_11_19 (
. . . . . . . . GISAID NA EPI271064
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa184,
. . . . . . . . syn416D (GAc))

. . . . KazakhstanAlmaty347_18M_2009_11_19 (
. . . . . . . . GISAID HA EPI271061
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . 124I [H1N1 Avian],
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)

. . . . KazakhstanAlmaty347_18M_2009_11_19 (
. . . . . . . . GISAID NA EPI271062
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa184,
. . . . . . . . syn416D (GAc))

. . . . KazakhstanAlmaty330_NP_4M_2009_11_17 (
. . . . . . . . GISAID HA EPI277095
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)

. . . . KazakhstanAlmaty330_NP_4M_2009_11_17 (
. . . . . . . . GISAID NA EPI277096
. . . . . . . . 2 Polymorphisms (0 Amino and 2 Silent)
. . . . . . . . NA Truncated before aa186,
. . . . . . . . syn259E (GAg)[H1N1 Avian],
. . . . . . . . syn416D (GAc))

. . . . KazakhstanAlmaty330_4M_2009_11_17 (
. . . . . . . . GISAID HA EPI271059
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . 142V,
. . . . . . . . syn194L (CTt) [H1N1 Avian],
. . . . . . . . HA Truncated after aa293)

. . . . KazakhstanAlmaty330_4M_2009_11_17 (
. . . . . . . . GISAID NA EPI271060
. . . . . . . . 2 Polymorphisms (0 Amino and 2 Silent)
. . . . . . . . NA Truncated before aa186,
. . . . . . . . syn259E (GAg) [H1N1 Avian],
. . . . . . . . syn416D (GAc))

. . . . ItalyPavia15_2009_07_20 (
. . . . . . . . GISAID HA EPI240761
. . . . . . . . 2 Polymorphisms (2 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa83,
. . . . . . . . 142V,
. . . . . . . . 225E,
. . . . . . . . HA Truncated after aa338)

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