2010-11-16

225Y from Finland Increases Depth of Genetic Diversity within Critical Receptor Binding Site

Last Updated 2010-12-11

The National Institute for Health and Welfare of Finland deposited a group of 133 HA sequences at GenBank on 2010-11-13. The amino acid range of position 225 is extended by the mixed peaks found on an unidentified age / gender sampled on 2009-11-28, Finland649_2009_11_28. Though 225E is the most common change at the position within this geography, this particular infection attempted immune escape by revising to a Tyrosine at 225.  This inflection point sample was taken at a peak of the pandemic practically one year ago and was not published until November 2010.

. . . . Finland649_2009_11_28 (
. . . . . . . . syn49G [MyanmarJPS020_2010_07_07
. . . . . . . . . . . . . . . . . . . . plus 8 in 2010,
. . . . . . . . . . . . . . India8910_2010-05-08
. . . . . . . . . . . . . . . . . . . . with 188T,
. . . . . . . . . . . . . . SingaporeKK081_2010_02_12,
. . . . . . . . . . . . . . TexasJMS411_2010_01_25
. . . . . . . . . . . . . . . . . . . . plus 2 in late 2009,
. . . . . . . . . . . . . . Virginia01_2010_01-21,
. . . . . . . . . . . . . . Hawaii01_2010_01-03,
. . . . . . . . . . . . . . Hawaii02_2010_01-02,
. . . . . . . . . . . . . . England935_2009_12,
. . . . . . . . . . . . . . Yakutsk_EAV_2009_11_18,
. . . . . . . . . . . . . . swIowa44837_1_2009_11_08_xL
. . . . . . . . . . . . . . . . . . . . with 225N, 230I,
. . . . . . . . . . . . . . CaliforniaVRDL71_2009_08_28,
. . . . . . . . . . . . . . WiscS0435_2009,
. . . . . . . . . . . . . . HK01_2009_04_30, et al],
. . . . . . . . syn216E,
. . . . . . . . 225Y mix wt (kAT),
. . . . . . . . 324I,
. . . . . . . . syn413K)

Another trace supporting this Finnish deposit showed a mix at 225 equating to 225G and wild type. Note the consecutive numbering of the 225Y sample to the 225G sample and the similarity of the two sequences.  Of the 5 morphic positions, they share 4 and have matching revision values at 3 of those 5.

. . . . Finland648_2009_11_19 (
. . . . . . . . 129Q,
. . . . . . . . syn216E,
. . . . . . . . 225G mix wt,
. . . . . . . . 324I,
. . . . . . . . syn413K)

Previously, we have detailed the genetic diversity and Vaccine Escape tendencies within this viral reservoir.  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 with position 225 increasing by the novel Tyrosine with the Finnish deposit.   Protein revision is documented at 58 of the 63 positions (92%), engaging a wide potential for antibody resistance (natural Immune Escape and Vaccine Escape).  Specifically, the range from 220 to 226 shows deep diversity, driving sequences that are laboratory confirmed as Low Reactors (Vaccine Escape).  With the critical position 225 depth chart now moving into double digits at 10 values within this reservoir, ample consideration must be given to the rapid acquisition feature on display.

Amino Acid Position 225 Variation in ΣPF11

  • 225D (GAt) wt
  • 225D synonymous (GAc)
  • 225A
  • 225E (GAa)
  • 225E (GAg)
  • 225E (GAa) plus 226R
  • 225G (Gga) from 225E
  • 225G (GgT)
  • 225N
  • 225V
  • 225Y

Supporting Sequences

. . . . Yakutsk_EAV_2009_11_18 (
. . . . . . . . syn49G,
. . . . . . . . syn164L [1918],
. . . . . . . . 206S [Yaro_CHMV_2009_11_10_f (224K & 225G)],
. . . . . . . . 286N [H3N8],
. . . . . . . . . . . [Yaro_CHMV],
. . . . . . . . 296H [Yaro_CHMV],
. . . . . . . . syn348V [Yaro_CHMV,
. . . . . . . . . . . . . . . IndiaPune10604_2009_09,
. . . . . . . . . . . . . . . BZ_SaoPaulo53823_2009_08_01_f,
. . . . . . . . . . . . . . . Eng662_2009_08],
. . . . . . . . syn429L (TTa) [H3N8 Avian, 1918, WSN33, S5, M7],
. . . . . . . . syn448L [S9],
. . . . . . . . . . . . . [Yaro_CHMV],
. . . . . . . . syn490P [S5, tn],
. . . . . . . . . . . . . [Yaro_CHMV],
. . . . . . . . syn511T [Yaro_CHMV],
. . . . . . . . syn542S [H2, H5, H9N2],
. . . . . . . . . . . . . [Yaro_CHMV])



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