Romania Demonstrates Zoonotic Potential Scores of 100% on HA 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
2011-07-18

The Cantacuzino Insttitute of Bucharest, Romania released sequences from 50 HA Segments and 2 unmatched NA segments at GenBank and GISAID on 2011-05-19.  The sample dates span 452 days from 2009-11-12 to 2011-02-07.  All 52 segment sequences are fragments and show extensive variation, including several with high Zoonotic Potential scores.  Template crossing is documented in this deposit.

Diverse geography is represented across this batch and an overall heavy zoonotic homology is found.  Animal reservoirs are represented including H9N2, H7N7, H5N1, H3N8 and H3N2.  With the Romanian HA polymorphisms, homology is found to H9N2 Human & Avian, to H7N7 Human, Avian and Equine, to H5N1 Emergent Human, to H3N8 Avian and to H3N2 Emergent Human from H3N2 Avian, Feline & Canine.  This group of sequences may, in time, be found to demonstrate significant zoonotic genetic re-seeding from the animal reservoirs at the 5’ ends of the fragments as well as the 3’ ends.

Zoonotic Potential

At least two sequences in this deposit demonstrate a 100% Zoonotic Potential score.  H5N1 homology is found on RomaniaConstanta330_2010_01_05, a 201 amino HA fragment from Winter 2010.  All 5 polymorphisms (2 Amino and 2 Silent) on this pH1N1 Romanian sequence are found in the H5N1 reservoir on various samples and the combination appears novel to pH1N1 and novel to H5N1.  The superset of changes on RomaniaCluj14972_2009_12_23 (205aa frag) may also be accommodated by the influence of zoonotic reservoirs.

Receptor Binding Site - HA aa225

HA aa225 polymorphisms are found in 6 instances, 225N (3) & 225G (3).

RomaniaConstanta50378_2011_01_21 (296aa frag) affixes HA 225N on an 188T (Clade 2) background with 100N and syn#8V, a position significant to the emergent Upsilon pH1N1 Sub-Clade (Clade 1: 189T).  RomaniaCarasSeverin663_2010_01_07 (173aa frag) carries 225N with 100N.  A singlet HA 225N appears on RomaniaPrahova2704_2010_01_18 (175aa frag) approximately one year earlier.

Another winter 2010 sequence, RomaniaSuceava406_2010_01_05 (196aa span), carries 225G with 2 zoonotic polymorphisms having homology to H3N2, H3N8, H7N7 Human and H9N2 Human.  On RomaniaBuzau14584_2009_12_21 (196aa frag), 225G is found with syn181G, a homology to H5N1 Human, H5N1 Emergent Avian and H9N2 Avian.  HA syn168Y, a regional pH1N1 marker from Russian and Ukrainian fatalities, appears 4 times, including a pairing with 225G on RomaniaPrahova564_2010_01_06 (172aa frag) and a pairing with 100N on RomaniaMaramures13812_2009_12_15 (198aa frag).

HA Template Jumping

In addition, clade-defining elements are observed appearing on different clade backgrounds, including RomaniaBihor51551_54F_2011_01_31 on a Clade 2 (188T Tau) background with the addition of 189T (Clade 1).  A Clade 5 (208K, 219V) background in 2011, RomaniaArad50090_2011_01_20 (287aa frag), received 188T (Clade 2).

Nine HA segment sequences spanning 2009_11_12 to 2010_01_26 measure zero polymorphisms.

Sequences

SortKeys:
SequenceDate Desc,
SequenceID Asc,
SegmentID Asc

. . . . RomaniaNeamt51999_2011_02_07 (
. . . . . . . . Clade 2: 188T
. . . . . . . . GISAID HA EPI317512
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . HA Truncated after aa287)

. . . . RomaniaBucuresti52010_2011_02_04 (
. . . . . . . . Clade 5: 208K, 219V
. . . . . . . . GISAID HA EPI317528
. . . . . . . . 11 Polymorphisms (6 Amino and 5 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . syn66G (GGg) [H5N1 wt, H6, H9N2],
. . . . . . . . syn82I (ATc),
. . . . . . . . syn93C (TGc) [H1N1 Avian wt],
. . . . . . . . . . . . . . . . . [H5N1 Avian Domestic & Wild],
. . . . . . . . . . . . . . . . . [H9N2 Avian Emergent 2009],
. . . . . . . . 100N,
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaBihor51551_54F_2011_01_31 (
. . . . . . . . Clade 2: 188T crossing with Clade 1: 189T
. . . . . . . . Sub-Clade Tau: 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . Tau Imputed: syn338G, syn448L, 454N
. . . . . . . . GISAID HA EPI317529
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 189T,
. . . . . . . . syn215P (CCa),
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaBrasov49666_2011_01_30 (
. . . . . . . . Clade 3: 186P
. . . . . . . . GISAID HA EPI317530
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . 137T,
. . . . . . . . 186P,
. . . . . . . . syn212K (AAa),
. . . . . . . . syn214K (AAa),
. . . . . . . . syn272D (GAc) [H1N1 Avian with pH1N1 Upsilon polymorphisms],
. . . . . . . . . . . . . . . . . . [H3N2 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian Emergent 2010],
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaBucuresti50820_2011_01_30 (
. . . . . . . . Clade 2: 188T
. . . . . . . . Sub-Clade Tau: 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . Tau Imputed: syn338G, syn448L, 454N
. . . . . . . . GISAID HA EPI317532
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . syn31H (CAt),
. . . . . . . . 73F,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn283Q (CAa),
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaArad51247_2011_01_29 (
. . . . . . . . Clade 5: 208K, 219V
. . . . . . . . GISAID HA EPI317518
. . . . . . . . 10 Polymorphisms (5 Amino and 5 Silent)
. . . . . . . . syn36L (tTA),
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . . . . . . . . . . . . [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],
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn292S (AGt),
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaArad51034_2011_01_29 (
. . . . . . . . Clade 2: 188T
. . . . . . . . Sub-Clade Tau: 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . Tau Imputed: syn338G, syn448L, 454N
. . . . . . . . GISAID HA EPI317531
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaSalaj51422_2011_01_28 (
. . . . . . . . Clade 2: 188T
. . . . . . . . Sub-Clade Tau: 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . Tau Imputed: syn338G, syn448L, 454N
. . . . . . . . GISAID HA EPI317505
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . 100N,
. . . . . . . . 174R,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . HA Truncated after aa295)

. . . . RomaniaCluj51505_2011_01_27 (
. . . . . . . . Clade 2: 188T
. . . . . . . . Sub-Clade Tau: 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . Tau Imputed: syn338G, syn448L, 454N
. . . . . . . . GISAID HA EPI317504
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaMures51180_2011_01_27 (
. . . . . . . . Clade 5: 208K, 219V
. . . . . . . . GISAID HA EPI317506
. . . . . . . . 9 Polymorphisms (4 Amino and 5 Silent)
. . . . . . . . syn36L (tTA),
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . . . . . . . . . . . . [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],
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn276H (CAt),
. . . . . . . . HA Truncated after aa295)

. . . . RomaniaBucuresti51194_2011_01_26 (
. . . . . . . . Clade 2: 188T
. . . . . . . . Sub-Clade Tau: 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . Tau Imputed: syn338G, syn448L, 454N
. . . . . . . . GISAID HA EPI317507
. . . . . . . . 4 Polymorphisms (2 Amino and 2 Silent)
. . . . . . . . 100N,
. . . . . . . . syn107Q (CAg),
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . HA Truncated after aa295)

. . . . RomaniaPrahova50643_2011_01_26 (
. . . . . . . . Clade 2: 188T
. . . . . . . . Sub-Clade Tau: 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . Tau Imputed: syn338G, syn448L, 454N
. . . . . . . . GISAID HA EPI317510
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . HA Truncated after aa287)

. . . . RomaniaBucuresti50823_2011_01_26 (
. . . . . . . . Clade 4: 128D
. . . . . . . . GISAID HA EPI317533
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . syn60I (ATc),
. . . . . . . . 107L,
. . . . . . . . 128D,
. . . . . . . . HA Truncated after aa295)

. . . . RomaniaCalarasi2225_2011_01_21 (
. . . . . . . . Clade 2: 188T
. . . . . . . . Sub-Clade Tau: 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . Tau Imputed: syn338G, syn448L, 454N
. . . . . . . . GISAID HA EPI317508
. . . . . . . . 4 Polymorphisms (2 Amino and 2 Silent)
. . . . . . . . 100N,
. . . . . . . . syn107Q (CAg),
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . HA Truncated after aa295)

. . . . RomaniaConstanta50378_2011_01_21 (
. . . . . . . . Clade 2: 188T
. . . . . . . . GISAID HA EPI317525
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . syn#8V (GTg),
. . . . . . . . syn32S (TCc),
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . 210G,
. . . . . . . . 225N,
. . . . . . . . syn232Y (TAc),
. . . . . . . . syn277D (GAc),
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaArad50090_2011_01_20 (
. . . . . . . . Clade 5: 208K, 219V crossing with Clade 2: 188T
. . . . . . . . GISAID HA EPI317509
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . syn36L (tTA),
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . . . . . . . . . . . . [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],
. . . . . . . . 188T,
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . HA Truncated after aa287)

. . . . RomaniaTimis49900_2011_01_19 (
. . . . . . . . GISAID HA EPI317501
. . . . . . . . 3 Polymorphisms (1 Amino and 2 Silent)
. . . . . . . . syn60I (ATc),
. . . . . . . . syn273T (ACg),
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaMaramures49545_2011_01_15 (
. . . . . . . . Clade 2: 188T
. . . . . . . . GISAID HA EPI317502
. . . . . . . . 3 Polymorphisms (3 Amino and 0 Silent)
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaIasi48801_2011_01_11 (
. . . . . . . . Clade 2: 188T
. . . . . . . . Sub-Clade Tau: 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . Tau Imputed: syn338G, syn448L, 454N
. . . . . . . . GISAID HA EPI317511
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 38G,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn292S (AGt),
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaBucuresti48333_2011_01_09 (
. . . . . . . . Clade 2: 188T
. . . . . . . . Sub-Clade Tau: 100N, syn179L, 188T,
. . . . . . . . . . . . . . . . Tau Imputed: syn338G, syn448L, 454N
. . . . . . . . GISAID HA EPI317503
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaBihor48551_2011_01_09 (
. . . . . . . . GISAID NA EPI317527
. . . . . . . . 5 Polymorphisms (1 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa253,
. . . . . . . . syn307N (AAt),
. . . . . . . . syn312Y (TAc),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa435)

. . . . RomaniaIasi47959_2010_12_31 (
. . . . . . . . GISAID NA EPI317526
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . NA Truncated before aa253,
. . . . . . . . syn330D (GAc),
. . . . . . . . 386S,
. . . . . . . . NA Truncated after aa435)

. . . . RomaniaPrahova3261_2010_01_26 (
. . . . . . . . GISAID HA EPI317487
. . . . . . . . 0 Polymorphisms (0 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa105,
. . . . . . . . HA Truncated after aa280)

. . . . RomaniaIasi2807_2010_01_19 (
. . . . . . . . GISAID HA EPI317486
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa105,
. . . . . . . . syn279N (AAc),
. . . . . . . . HA Truncated after aa280)

. . . . RomaniaPrahova2704_2010_01_18 (
. . . . . . . . GISAID HA EPI317485
. . . . . . . . 1 Polymorphisms (1 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa105,
. . . . . . . . 225N,
. . . . . . . . HA Truncated after aa280)

. . . . RomaniaNeamt2058_2010_01_13 (
. . . . . . . . GISAID HA EPI317484
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa105,
. . . . . . . . syn140P (CCc),
. . . . . . . . HA Truncated after aa280)

. . . . RomaniaCarasSeverin663_2010_01_07 (
. . . . . . . . GISAID HA EPI317491
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa100,
. . . . . . . . 100N,
. . . . . . . . 225N,
. . . . . . . . syn270I (ATc),
. . . . . . . . HA Truncated after aa273)

. . . . RomaniaBistritaNasaud677_2010_01_07 (
. . . . . . . . GISAID HA EPI317492
. . . . . . . . 4 Polymorphisms (1 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa93,
. . . . . . . . syn96G (GGg) [H1N1 Avian with pH1N1 Upsilon polymorphisms],
. . . . . . . . . . . . . . . . . [H5N1 Human and Avian wt],
. . . . . . . . . . . . . . . . . [H9N2 Human and Avian wt],
. . . . . . . . 100N,
. . . . . . . . syn220R (AGg) [H1N1 Avian with extensive pH1N1 polymorphisms],
. . . . . . . . . . . . . . . . . . [H3N2 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human],
. . . . . . . . . . . . . . . . . . [H9N2 Human and Avian wt],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . syn270I (ATc),
. . . . . . . . HA Truncated after aa273)

. . . . RomaniaIlfov481_2010_01_06 (
. . . . . . . . GISAID HA EPI317488
. . . . . . . . 4 Polymorphisms (2 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa137,
. . . . . . . . syn167S (TCt),
. . . . . . . . syn294P (CCc) [H3N2 Human emergent 2010 dropping 295F (TTc)],
. . . . . . . . . . . . . . . . . . [H3N2 Avian, Canine & Feline],
. . . . . . . . . . . . . . . . . . [H3N8 Avian wt],
. . . . . . . . . . . . . . . . . . [H7N7 Human, Avian and Equine wt],
. . . . . . . . . . . . . . . . . . [H9N2 Human 2009 with Upsilon polymorphisms],
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . 297S,
. . . . . . . . HA Truncated after aa297)

. . . . RomaniaPrahova564_2010_01_06 (
. . . . . . . . GISAID HA EPI317489
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa100,
. . . . . . . . syn168Y (TAt),
. . . . . . . . 225G,
. . . . . . . . HA Truncated after aa272)

. . . . RomaniaGalati591_2010_01_06 (
. . . . . . . . GISAID HA EPI317490
. . . . . . . . 0 Polymorphisms (0 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa110,
. . . . . . . . HA Truncated after aa276)

. . . . RomaniaConstanta330_2010_01_05 (
. . . . . . . . Zoonotic Potential: 100%
. . . . . . . . GISAID HA EPI317480
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa92,
. . . . . . . . syn96G (GGg) [H1N1 Avian with pH1N1 Upsilon polymorphisms],
. . . . . . . . . . . . . . . . . [H5N1 Human and Avian wt],
. . . . . . . . . . . . . . . . . [H9N2 Human and Avian wt],
. . . . . . . . 127S [H5N1 Egypt wt],
. . . . . . . . 166E [H5N1 Egypt Emergent Human 2010],
. . . . . . . . syn181G (GGa) [H5N1 Egypt Human 2007, 2009],
. . . . . . . . . . . . . . . . . . . . . . [H5N1 Avian Emergent 2010],
. . . . . . . . . . . . . . . . . . . . . . [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . . . . . with 39E, syn42G, 296R mix wt],
. . . . . . . . syn258F (TTt) [pH1N1 rare GISAID (under 30)],
. . . . . . . . . . . . . . . . . . [pH1N1 GISAID Low Homology to this Sequence],
. . . . . . . . . . . . . . . . . . [pH1N1 GISAID 4 with VxX Markers],
. . . . . . . . . . . . . . . . . . [H1N1 Avian with pH1N1 Upsilon polymorphisms],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2009 (Tat)],
. . . . . . . . HA Truncated after aa293)

. . . . RomaniaSuceava406_2010_01_05 (
. . . . . . . . GISAID HA EPI317481
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa101,
. . . . . . . . 225G,
. . . . . . . . syn294P (CCc) [H3N2 Human emergent 2010 dropping 295F (TTc)],
. . . . . . . . . . . . . . . . . . [H3N2 Avian, Canine & Feline],
. . . . . . . . . . . . . . . . . . [H3N8 Avian wt],
. . . . . . . . . . . . . . . . . . [H7N7 Human, Avian and Equine wt],
. . . . . . . . . . . . . . . . . . [H9N2 Human 2009 with Upsilon polymorphisms],
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . 297S,
. . . . . . . . HA Truncated after aa297)

. . . . RomaniaBotosani169_2010_01_03 (
. . . . . . . . GISAID HA EPI317479
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa91,
. . . . . . . . 91S [H3N2 Asia Avian],
. . . . . . . . . . . [H3N2 Human wt (aGc)],
. . . . . . . . 93F,
. . . . . . . . syn95P (CCc) [H1N1 Avian wt],
. . . . . . . . . . . . . . . . . [H3N2 Human and Avian wt (agc)],
. . . . . . . . . . . . . . . . . [H9N2 Early Human],
. . . . . . . . . . . . . . . . . [H9N2 Avian wt],
. . . . . . . . syn96G (GGg) [H1N1 Avian with pH1N1 Upsilon polymorphisms],
. . . . . . . . . . . . . . . . . [H5N1 Human and Avian wt],
. . . . . . . . . . . . . . . . . [H9N2 Human and Avian wt],
. . . . . . . . 99L,
. . . . . . . . 100V,
. . . . . . . . HA Truncated after aa289)

. . . . RomaniaOlt114_2010_01_02 (
. . . . . . . . GISAID HA EPI317465
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa105,
. . . . . . . . syn270I (ATc),
. . . . . . . . HA Truncated after aa280)

. . . . RomaniaOlt119_2010_01_02 (
. . . . . . . . GISAID HA EPI317466
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa105,
. . . . . . . . syn270I (ATc),
. . . . . . . . HA Truncated after aa280)

. . . . RomaniaBotosani15520_2009_12_30 (
. . . . . . . . GISAID HA EPI317476
. . . . . . . . 0 Polymorphisms (0 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa100,
. . . . . . . . HA Truncated after aa280)

. . . . RomaniaCluj15569_2009_12_30 (
. . . . . . . . GISAID HA EPI317477
. . . . . . . . 4 Polymorphisms (2 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa100,
. . . . . . . . 100N,
. . . . . . . . 111L [H3N2 Human and Avian wt (cTa)],
. . . . . . . . . . . . . [H9N2 Avian Emergent with pH1N1 polymorphisms (tct)],
. . . . . . . . syn251L (tTA),
. . . . . . . . syn270I (ATc),
. . . . . . . . HA Truncated after aa280)

. . . . RomaniaBraila15575_2009_12_30 (
. . . . . . . . GISAID HA EPI317478
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa97,
. . . . . . . . 99M (ATg) [H1N1 Avian with pH1N1 polymorphisms],
. . . . . . . . . . . . . . . [H9N2 Human 2000],
. . . . . . . . . . . . . . . [H9N2 Asia and Europe Avian (gag)],
. . . . . . . . syn135V (GTg),
. . . . . . . . syn168Y (TAt),
. . . . . . . . syn294P (CCc) [H3N2 Human emergent 2010 dropping 295F (TTc)],
. . . . . . . . . . . . . . . . . . [H3N2 Avian, Canine & Feline],
. . . . . . . . . . . . . . . . . . [H3N8 Avian wt],
. . . . . . . . . . . . . . . . . . [H7N7 Human, Avian and Equine wt],
. . . . . . . . . . . . . . . . . . [H9N2 Human 2009 with Upsilon polymorphisms],
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaBotosani15033_2009_12_26 (
. . . . . . . . GISAID HA EPI317474
. . . . . . . . 0 Polymorphisms (0 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa100,
. . . . . . . . HA Truncated after aa291)

. . . . RomaniaDambovita15050_2009_12_26 (
. . . . . . . . GISAID HA EPI317475
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa91,
. . . . . . . . 91S [H3N2 Asia Avian],
. . . . . . . . . . . [H3N2 Human wt (aGc)],
. . . . . . . . syn96G (GGg) [H1N1 Avian with pH1N1 Upsilon polymorphisms],
. . . . . . . . . . . . . . . . . [H5N1 Human and Avian wt],
. . . . . . . . . . . . . . . . . [H9N2 Human and Avian wt],
. . . . . . . . HA Truncated after aa288)

. . . . RomaniaCluj14972_2009_12_23 (
. . . . . . . . Zoonotic Potential: 100%
. . . . . . . . GISAID HA EPI317473
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa91,
. . . . . . . . 91S [H3N2 Asia Avian],
. . . . . . . . . . . [H3N2 Human wt (aGc)],
. . . . . . . . syn96G (GGg) [H1N1 Avian with pH1N1 Upsilon polymorphisms],
. . . . . . . . . . . . . . . . . [H5N1 Human and Avian wt],
. . . . . . . . . . . . . . . . . [H9N2 Human and Avian wt],
. . . . . . . . 99M (ATg) [H1N1 Avian with pH1N1 polymorphisms],
. . . . . . . . . . . . . . . [H9N2 Human 2000],
. . . . . . . . . . . . . . . [H9N2 Asia and Europe Avian (gag)],
. . . . . . . . syn272D (GAc) [H1N1 Avian with pH1N1 Upsilon polymorphisms],
. . . . . . . . . . . . . . . . . . [H3N2 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian Emergent 2010],
. . . . . . . . syn294P (CCc) [H3N2 Human emergent 2010 dropping 295F (TTc)],
. . . . . . . . . . . . . . . . . . [H3N2 Avian, Canine & Feline],
. . . . . . . . . . . . . . . . . . [H3N8 Avian wt],
. . . . . . . . . . . . . . . . . . [H7N7 Human, Avian and Equine wt],
. . . . . . . . . . . . . . . . . . [H9N2 Human 2009 with Upsilon polymorphisms],
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaIasi14805_2009_12_22 (
. . . . . . . . GISAID HA EPI317471
. . . . . . . . 1 Polymorphisms (0 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa96,
. . . . . . . . syn96G (GGg) [H1N1 Avian with pH1N1 Upsilon polymorphisms],
. . . . . . . . . . . . . . . . . [H5N1 Human and Avian wt],
. . . . . . . . . . . . . . . . . [H9N2 Human and Avian wt],
. . . . . . . . HA Truncated after aa291)

. . . . RomaniaIlfov14852_2009_12_22 (
. . . . . . . . GISAID HA EPI317472
. . . . . . . . 4 Polymorphisms (2 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa98,
. . . . . . . . 99M (ATg) [H1N1 Avian with pH1N1 polymorphisms],
. . . . . . . . . . . . . . . [H9N2 Human 2000],
. . . . . . . . . . . . . . . [H9N2 Asia and Europe Avian (gag)],
. . . . . . . . syn168Y (TAt),
. . . . . . . . syn294P (CCc) [H3N2 Human emergent 2010 dropping 295F (TTc)],
. . . . . . . . . . . . . . . . . . [H3N2 Avian, Canine & Feline],
. . . . . . . . . . . . . . . . . . [H3N8 Avian wt],
. . . . . . . . . . . . . . . . . . [H7N7 Human, Avian and Equine wt],
. . . . . . . . . . . . . . . . . . [H9N2 Human 2009 with Upsilon polymorphisms],
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . HA Truncated after aa296)

. . . . RomaniaBuzau14584_2009_12_21 (
. . . . . . . . GISAID HA EPI317470
. . . . . . . . 3 Polymorphisms (2 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa97,
. . . . . . . . syn181G (GGa) [H5N1 Egypt Human 2007, 2009],
. . . . . . . . . . . . . . . . . . . . . . [H5N1 Avian Emergent 2010],
. . . . . . . . . . . . . . . . . . . . . . [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . . . . . with 39E, syn42G, 296R mix wt],
. . . . . . . . 182V,
. . . . . . . . 225G,
. . . . . . . . HA Truncated after aa293)

. . . . RomaniaMures14446_2009_12_20 (
. . . . . . . . GISAID HA EPI317469
. . . . . . . . 1 Polymorphisms (1 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa124,
. . . . . . . . 255K,
. . . . . . . . HA Truncated after aa268)

. . . . RomaniaMaramures13812_2009_12_15 (
. . . . . . . . GISAID HA EPI317468
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa99,
. . . . . . . . 99R,
. . . . . . . . 100N,
. . . . . . . . syn168Y (TAt),
. . . . . . . . syn294P (CCc) [H3N2 Human emergent 2010 dropping 295F (TTc)],
. . . . . . . . . . . . . . . . . . [H3N2 Avian, Canine & Feline],
. . . . . . . . . . . . . . . . . . [H3N8 Avian wt],
. . . . . . . . . . . . . . . . . . [H7N7 Human, Avian and Equine wt],
. . . . . . . . . . . . . . . . . . [H9N2 Human 2009 with Upsilon polymorphisms],
. . . . . . . . 296R (Cgc) [H9N2 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 39E, syn42G, syn181G, 296R mix wt],
. . . . . . . . 297S,
. . . . . . . . HA Truncated after aa297)

. . . . RomaniaHarghita12170_2009_12_08 (
. . . . . . . . GISAID HA EPI317467
. . . . . . . . 0 Polymorphisms (0 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa114,
. . . . . . . . HA Truncated after aa273)

. . . . RomaniaIasi11140_2009_12_02 (
. . . . . . . . GISAID HA EPI317464
. . . . . . . . 0 Polymorphisms (0 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa107,
. . . . . . . . HA Truncated after aa246)

. . . . RomaniaBotosani10121_2009_11_26 (
. . . . . . . . GISAID HA EPI317463
. . . . . . . . 0 Polymorphisms (0 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa135,
. . . . . . . . HA Truncated after aa281)

. . . . RomaniaIasi9422_2009_11_22 (
. . . . . . . . GISAID HA EPI317483
. . . . . . . . 0 Polymorphisms (0 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa105,
. . . . . . . . HA Truncated after aa272)

. . . . RomaniaBotosani8204_2009_11_12 (
. . . . . . . . GISAID HA EPI317482
. . . . . . . . 0 Polymorphisms (0 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa107,
. . . . . . . . HA Truncated after aa280)

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France Highlights Polymorphic Fluctuation in 83 Day Series

Sequences discussed in this analysis are variously stored publicly at GenBank and at GISAID. We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GenBank and from GISAID’s EpiFlu™ Database on which this research is based. A GISAID-generated list is detailed in a linked spreadsheet for completeness in citation.

Last Update
2011-07-18

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

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

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

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

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

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

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

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

Sequences

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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TamiFlu Resistant Australian Sequences Demonstrate Recombination with Human and Avian H5N1

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.

1. Hurt AC, Lee RT, Leang SK, Cui L, Deng YM, Phuah SP, Caldwell N, Freeman K, Komadina N, Smith D, Speers D, Kelso A, Lin RT, Maurer-Stroh S, Barr IG. Increased detection in Australia and Singapore of a novel influenza A(H1N1)2009 variant with reduced oseltamivir and zanamivir sensitivity due to a S247N neuraminidase mutation. Euro Surveill. 2011;16(23):pii=19884.
Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19884
Date of submission: 26 May 2011

“A novel influenza A(H1N1)2009 variant with mildly reduced oseltamivir and zanamivir sensitivity has been detected in more than 10% of community specimens in Singapore and more than 30% of samples from northern Australia during the early months of 2011.”¹

Last Updated
2011-06-16

On 2011-06-02, the WHO Collaborating Centre for Reference and Research on Influenza published 10 HA and 12 NA pH1N1 sequence segments at GISAID in support of their paper ¹ on the MultiDrug Resistance moderated by NA 247N.  These sequences were sampled from patients in Australia and Brunei from January to March 2011.  In addition to the discussed NA 247N, all 12 Neuraminidase segments display multiple polymorphism recombination at the 5’ end with a zoonotic co-infection from a strain matching Human and Avian H5N1 cases as well as H4, H6, H9N2, H10, H11, H12 and H13 sequences.  The Brunei sequence exhibits potential recombination to the same zoonotic reservoirs with additional NA nucleotide homology at aa40, aa46, aa95, 157T, aa353, 369K, aa377 and aa426.

These sequences are deeply avian in nature with additional homology to various zoonotic reservoirs.  Though the primary subclade carrying this drug resistance marker is young, the basic backbone has risen to triple digits rather quickly.  The HA and the NA segments in this deposit represent hypermorphic outcomes signaling a change in viral behaviour on SubClade 5 (208K_219V) in this region of the world during early 2011.  Notice must be made that the NA 247N has crossed onto the HA 188T SubClade as well.  Existence of the newly recognised TamiFlu resistance marker across multiple human pandemic subclades indicates potential for spread.

As we have previously discussed concerning genetic markers for drug resistance, GeneWurx expects standing genetic revisions on the pH1N1 subclades to eventually be laboratory validated for drug resistance.

. . . . AustraliaDarwin75_27F_2011_03_17 (
. . . . . . . . GISAID HA EPI319199
. . . . . . . . 17 Polymorphisms (8 Amino and 9 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . 262K [H5N1 Human (Aag)],
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn549R (AGg))

. . . . AustraliaDarwin75_27F_2011_03_17 (
. . . . . . . . GISAID NA EPI319198
. . . . . . . . 12 Polymorphisms (4 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 299A,
. . . . . . . . 466R,
. . . . . . . . 467S)

. . . . AustraliaDarwin75_MDCK1_27F_2011_03_17 (
. . . . . . . . GISAID HA EPI319166
. . . . . . . . 15 Polymorphisms (8 Amino and 7 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . 262K [H5N1 Human (Aag)],
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933])

. . . . AustraliaDarwin75_MDCK1_27F_2011_03_17 (
. . . . . . . . GISAID NA EPI319165
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 299A)

. . . . AustraliaDarwin74_17F_2011_03_16 (
. . . . . . . . GISAID HA EPI319170
. . . . . . . . 17 Polymorphisms (8 Amino and 9 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn549R (AGg),
. . . . . . . . 550S)

. . . . AustraliaDarwin74_17F_2011_03_16 (
. . . . . . . . GISAID NA EPI319169
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 299A)

. . . . AustraliaDarwin74_MDCK1_17F_2011_03_16 (
. . . . . . . . GISAID HA EPI319182
. . . . . . . . 14 Polymorphisms (6 Amino and 8 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918])

. . . . AustraliaDarwin74_MDCK1_17F_2011_03_16 (
. . . . . . . . GISAID NA EPI319181
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 299A)

. . . . AustraliaPerth29_40M_2011_03_08_TmX_f (
. . . . . . . . GISAID HA EPI319176
. . . . . . . . 16 Polymorphisms (8 Amino and 8 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . 259V,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918])

. . . . AustraliaPerth29_40M_2011_03_08_TmX_f (
. . . . . . . . GISAID NA EPI319175
. . . . . . . . 11 Polymorphisms (3 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 299A)

. . . . AustraliaDarwin54_26M_2011_03_06 (
. . . . . . . . GISAID NA EPI319184
. . . . . . . . 9 Polymorphisms (1 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms])

. . . . AustraliaPerth30_40M_2011_03_01_f (
. . . . . . . . GISAID HA EPI319178
. . . . . . . . 16 Polymorphisms (8 Amino and 8 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . 259V,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918])

. . . . AustraliaPerth30_40M_2011_03_01_f (
. . . . . . . . GISAID NA EPI319177
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 299A)

. . . . AustraliaDarwin70_20F_2011_02_14 (
. . . . . . . . GISAID HA EPI319174
. . . . . . . . 15 Polymorphisms (7 Amino and 8 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918])

. . . . AustraliaDarwin70_20F_2011_02_14 (
. . . . . . . . GISAID NA EPI319173
. . . . . . . . 11 Polymorphisms (3 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 299A,
. . . . . . . . 466R)

. . . . AustraliaDarwin11_27F_2011_02_11 (
. . . . . . . . GISAID NA EPI319183
. . . . . . . . 11 Polymorphisms (2 Amino and 9 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 299A,
. . . . . . . . syn433E (GAa) [H3N1 Swine],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms])

. . . . AustraliaDarwin10_37M_2011_02_09 (
. . . . . . . . GISAID HA EPI319172
. . . . . . . . 15 Polymorphisms (7 Amino and 8 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918])

. . . . AustraliaDarwin10_37M_2011_02_09 (
. . . . . . . . GISAID NA EPI319171
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 299A)

. . . . AustraliaDarwin2_CS_18M_2011_01_13 (
. . . . . . . . GISAID HA EPI319168
. . . . . . . . 16 Polymorphisms (8 Amino and 8 Silent)
. . . . . . . . 41D,
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918])

. . . . AustraliaDarwin2_CS_18M_2011_01_13 (
. . . . . . . . GISAID NA EPI319167
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 299A)

. . . . AustraliaDarwin2_18M_2011_01_13 (
. . . . . . . . GISAID HA EPI302351
. . . . . . . . 16 Polymorphisms (8 Amino and 8 Silent)
. . . . . . . . 41D,
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918])

. . . . AustraliaDarwin2_18M_2011_01_13 (
. . . . . . . . GISAID NA EPI302350
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1_υ polymorphisms],
. . . . . . . . 299A)

. . . . Brunei1_2011_01_13 (
. . . . . . . . GISAID HA EPI319180
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc) [H5N1 Human 2011],
. . . . . . . . 377K,
. . . . . . . . syn388K (AAa) [H5N1 Human 2005, 2011],
. . . . . . . . 454N,
. . . . . . . . syn527L (TTa) [H5N1 Human 2005, 2011 (cTa)])

. . . . Brunei1_2011_01_13 (
. . . . . . . . GISAID NA EPI319179
. . . . . . . . 14 Polymorphisms (6 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . 40I [H1N1 Avian
. . . . . . . . . . . . . .  with pH1N1_υ polymorphisms],
. . . . . . . . 46T [H1N1 Avian
. . . . . . . . . . . . . .  with pH1N1_υ polymorphisms],
. . . . . . . . . . . [H1N1 Camel],
. . . . . . . . 95I,
. . . . . . . . syn157T (ACt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn240T (ACc) [H1N1 Avian wt],
. . . . . . . . 241I [H1N1 Avian wt],
. . . . . . . . 247N,
. . . . . . . . syn353Y (TAt) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with pH1N1_υ polymorphisms],
. . . . . . . . 369K [H1N1 Avian
. . . . . . . . . . . . . . . . with pH1N1_υ polymorphisms],
. . . . . . . . . . . . [H4N6 Avian 2010],
. . . . . . . . . . . . [H12N6 Avian],
. . . . . . . . syn377P (CCa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with pH1N1_υ polymorphisms],
. . . . . . . . syn426L (tTA) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with pH1N1_υ polymorphisms])

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