HA 225G Paired with 156E & 188T in Diverse Deposit from Australia

Last Updated 2010-12-16

A WHO Collaborating Centre for Reference and Research on Influenza released a large group of sequences at GISAID on 2010-12-14 primarily from Australia. 225G appears on two different backgrounds during the same timeframe, one with the H7N7 polymorphism that has been associated with viral conjunctivitis, 188T.  OzBrisbane209_51F_2010_08_09 also demonstrates a 156E polymorphism just upstream from the section at aa158 and aa159 that has produced so many "Low Reactor" / Vaccine Escape strains.

156E was found in the 1976 Swine Flu with 225G, but until now has not been documented in the pH1N1 with 225G, though the individual change has been located in 9 sequences [New Zealand, Japan (2), China 2010, Hungary, Germany (2) and the United States (2)].  Changes at residues 156, 157 and 158 are known to increase viral replication speed and success on the pandemic H1N1 background.  At the MedImmune growth speed experiments preparing for the 2009 Live Attenuated Influenza Vaccine, the combination of 156E and 225G created the highest pathological output (V5-153E) (J Virol. 2010 January; 84(1): 44–51). Though the V5-153E strain produced the most beneficial viral output, the lineage was impeached due to a 16 fold titers reduction in the antigenicity tests indicating a profound level of "Low Reactor".
 
This Brisbane sample has not yet been tagged for Vaccine Escape.

As a set of coincident events, several zoonotic Influenza reservoirs have also gained 156E in recent years.  This group of reservoirs appears to parallel individual changes coming into the human H1N1 pandemic.  H5N1 human cases in Vietnam carry this change from 2004.  The most current updates of Avian sequences from Egypt H5N1 in 2009 up to July 2010 demonstrate emergent 156E with 225G (Ggg).  One particular Egyptian bird, ckEgypt10135ss_2010_03, shows 156E, 225G and a variant coding for syn338G (GGg).

H3N8 equine and swine samples are on record producing this emergent change.  H7N3 and H7N7 each provide material for nucleotide donation at the first codon base while an extensive percentage of the H10N7 sequences on file carry the 156E.  A hybrid swine H1N1 sequence from Iowa,
swIowa44837_1_2009_11_08_xL, was recently published after a one year lag with 156E, 188R, 225N, 230I & syn346G.

This Brisbane strain is emergent and aggregates 225G with markers found throughout the coastal United States during late 2009 and 2010.  On a similar note, a sub-clade may perhaps be forming from Jiangsu Province, China using 225G paired with 158E and a change at amino acid position 454.

The 215T found in the sequence from the 9 year old boy, Sydney202_9M_2010_07_18, confirms an increase in the genetic diversity of the post-pandemic reservoir found during the official pandemic on an eastern European sequence, PolandWarsawINS316_2009_12_08.

As we have previously reported, 100% of the Hemagglutinin positions between 186 and 248, including antigenic areas of the Receptor Binding Domain (RBD/RBS), are on record as polymorphic. No position in that range is stable.  Many positions rate multiple changes.  Protein revision is documented at 60 of the 63 positions (95%), engaging the potential for antibody resistance (natural immune escape and vaccine escape). 

. . . . OzBrisbane209_51F_2010_08_09 (
. . . . . . . . 156E [H2N3, H3N8, H5N1, H10N7],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . 225G,
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . . . . . . . . [OzVictoria670_30M_2010_11_14
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . Emergent across Australia
. . . . . . . . . . . . . . . . . . . . . during late 2010 season,
. . . . . . . . . . . . . . . Florida14_24M_2010_08_05
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . OZVictoria512_2010_07_30
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . NZChristchurch15_2010_07_12
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . India5107_2010_06_28
. . . . . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . . . . . . MississippiAF2474_2010_03_10
. . . . . . . . . . . . . . . . . . . . . with syn235T,
. . . . . . . . . . . . . . . FloridaAF2197_2010_03_07
. . . . . . . . . . . . . . . . . . . . . with 156T,
. . . . . . . . . . . . . . . CalifVRDL9_2010_02_09
. . . . . . . . . . . . . . . . . . . . . with syn193S,
. . . . . . . . . . . . . . . Georgia06_2010_02_05
. . . . . . . . . . . . . . . . . . . . . with syn161Y,
. . . . . . . . . . . . . . . NY4662_2010_02_03
. . . . . . . . . . . . . . . . . . . . . with 97N, syn276H, syn283Q, syn304G,
. . . . . . . . . . . . . . . TexasJMS406_2010_01_10
. . . . . . . . . . . . . . . . . . . . . with 187A, syn193S, syn283Q,
. . . . . . . . . . . . . . . TexasJMS405_2010_01_09
. . . . . . . . . . . . . . . . . . . . . with 187A, syn283Q,
. . . . . . . . . . . . . . . CalifVRDL131_2009_12_30
. . . . . . . . . . . . . . . . . . . . . with 225G, syn455Q,
. . . . . . . . . . . . . . . LouisianaAF2435_2009_11_30
. . . . . . . . . . . . . . . . . . . . . with syn13N,
. . . . . . . . . . . . . . . Vienna291_2009_11_19
. . . . . . . . . . . . . . . catOregon29573_2009_11_09
. . . . . . . . . . . . . . . . . . . . . with 226R, syn283Q,
. . . . . . . . . . . . . . . Calif_SanDiegoINS63_2009_10_26
. . . . . . . . . . . . . . . . . . . . . with syn283Q, et al],
. . . . . . . . 377K,
. . . . . . . . 454N [H7N3, H7N7, H9N2]
. . . . . . . . . . [Florida14_24M_2010_08_05
. . . . . . . . . . . . . . . . . . with 188T, 454N,
. . . . . . . . . . FL_Pen210_2009_11_10
. . . . . . . . . . . . . . . . . . with 225E,
. . . . . . . . . . SouthCarolina18_2009_09_16_VxX
. . . . . . . . . . . . . . . . . . with 159D, 224K,
. . . . . . . . . . Texas45131774_2009_09_13
. . . . . . . . . . . . . . . . . . with syn223V,
. . . . . . . . . . IndiaPune9355_2009_08
. . . . . . . . . . . . . . . . . . with 225G,
. . . . . . . . . . IndiaBlore236_2009_06_xL
. . . . . . . . . . . . . . . . . . with 226R, et al],
. . . . . . . . syn465N)

. . . . Sydney202_9M_2010_07_18 (
. . . . . . . . 34D,
. . . . . . . . syn44L,
. . . . . . . . 97N,
. . . . . . . . syn106E,
. . . . . . . . 128D,
. . . . . . . . 215T [PolandWarsawINS316_2009_12_08]
. . . . . . . . 225G,
. . . . . . . . 253A,
. . . . . . . . syn362S,
. . . . . . . . 377K,
. . . . . . . . 439G [Guangdong5024_2009_10_20])

Supporting Sequences

. . . . Florida14_24M_2010_08_05 (
. . . . . . . . 100N [H7N3, H7N7, H9N2],
. . . . . . . . syn161Y [H3N8 2009, H6N1, H9N2],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 442I mix,
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . OZVictoria512_2010_07_30 (
. . . . . . . . syn60I,
. . . . . . . . 100N [H7N3, H7N7, H9N2],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn285P,
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . Thailand34_9912_2010_07_14 (
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . 200T,
. . . . . . . . HA truncated after aa253)

. . . . Thailand34_9937_2010_07_14 (
. . . . . . . . 162Q [Unique to PF11 GenBank/GISAID],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . HA truncated after aa253)

. . . . NZChristchurch15_2010_07_12 (
. . . . . . . . 100N,
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . India5107_2010_06_28 (
. . . . . . . . syn60I,
. . . . . . . . 100N [H7N3, H7N7, H9N2],
. . . . . . . . syn135V,
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . India8910_2010_05_08 (
. . . . . . . . syn49G [H7N3, H7N7],
. . . . . . . . syn51A,
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . swThaiCURA75_2010_01 (
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . 263D,
. . . . . . . . syn350G [H7N3, H7N7],
. . . . . . . . 414I,
. . . . . . . . syn484N [H3N8, H4, H5N1 (E/A/H), H6, H7N7, H9N2, H11])

. . . . Texas45131774_2009_09_13 (
. . . . . . . . syn223V [H5N1, H6N1],
. . . . . . . . 454N [H7N3, H7N7, H9N2]
. . . . . . . . . . . . . . [IndiaPune9355_2009_08 with 225G,
. . . . . . . . . . . . . . IndiaBlore236_2009_06 with 226R,
. . . . . . . . . . . . . . SouthCarolina18_2009_09_16_VxX with 224K,
. . . . . . . . . . . . . . FL_Pen210_2009_11_10 with 225E])

. . . . PolandWarsawINS316_2009_12_08 (
. . . . . . . . 22I,
. . . . . . . . syn92T,
. . . . . . . . 119M,
. . . . . . . . 165N,
. . . . . . . . syn178V,
. . . . . . . . syn186S,
. . . . . . . . 215T,
. . . . . . . . syn256Y,
. . . . . . . . syn275V,
. . . . . . . . 463V)

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