228R from Iran Increases Critical Receptor Binding Domain Diversity Above 90%

Last Updated 2010-10-26

In positions where this flu is revising the pandemic gene code, the ΣPF11 reservoir (pH1N1) presently exhibits a strong pattern of alliance with serotypes normally infecting birds, horses and dogs.

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 now documented at 57 of the 63 positions (90%), engaging the potential for antibody resistance (natural immune escape and vaccine escape). 

The Shiraz University of Medical Science released a group of sequences today at GenBank.  Each demonstrates unusual characteristics.  One stands above the others.  IranShiraz1_2010_02 carries a previously unseen Receptor Binding Domain revision, 228R, alongside changes found recently in the H10N7 reservoir. Of interest is the fact that changes at or around amino acid position 238 and changes at or around 275 are associated with an emerging sub-clade that is permissive to and demonstrates the M230I polymorphism.

Is 228R another tertiary Immune Escape marker similar in mechanism to 230I?  Iran has also documented 227Q in the reservoir on a hyper-morphic sample, Iran15583_2009_11_21.

. . . . IranShiraz1_2010_02 (
. . . . . . . . 88T,
. . . . . . . . 90K,
. . . . . . . . 91W,
. . . . . . . . syn218A [WSN33],
. . . . . . . . . . . . . . . [Nebraska02_2010_03_11
. . . . . . . . . . . . . . . . . . . . . .with 523A,
. . . . . . . . . . . . . . . CubaHabana2687_2009
. . . . . . . . . . . . . . . . . . . . . .with 221T]
. . . . . . . . 228R (cGG) [H9N2 2008 (AGA)],
. . . . . . . . 238Q [H10N7 2009],
. . . . . . . . 246Q,
. . . . . . . . 277N [H5N1, H10N7 2009],
. . . . . . . . . . . . . [Iran15583_2009_11_21,
. . . . . . . . . . . . . Wisconsin],
. . . . . . . . syn350G [swThaiCURA4_2009_11
. . . . . . . . . . . . . . . . . . . with 226R, syn484N])

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230I Permissive Sub-Clade Expanded via June 2010 Sequence from South Africa

Last Updated 2010-10-16

Another distinct geographic area is inserted into the January to August 2010 Expansion of the emerging 230I-Permissive PF11 Hydra.

From 2010-08-07 through 2010-09-27, GeneWurx discussed the spread of one remarkable Hydra across the US, Germany and the Ukraine.  HA 230I is represented in this sub-clade on a sequence from the US state of Minnesota.  HA 225G (GGt) entered the sub-clade in the US state of Pennsylvania.  The sub-clade appears to be one of several that are permissive to a combination of 225G (GGt) and 230I within post-pandemic H1N1.

On 2010-10-14, the UK National Institute for Medical Research released a set of sequences at GISAID, primarily from Africa.  CapeTown29_24M_2010_06_08, originated by the Sandringham National Institute for Communicable Disease, was sampled from a 24 year old male.  No clinical information is provided, nor outcome. 

The sequence carries 9 polymorphisms on the HA alone and typifies the rapid genetic acquisition.  Six of those changes place the sequence with 12 other cases across the United States, the Ukraine and Germany.

Follow 6 HA polymorphisms (3 silent) tracing onto this 13th sequence through the 9th distinct geographic location:

34D, 165N, 189T, syn213F, syn305K, syn346G.

Five of the six polymorphisms are found in animal influenza reservoirs (zoonotic) and the sixth shares nucleotide homology with recognised zoonotic reservoirs.  Does this Hydra link the US to flu strains from the Ukraine, India or Russia?

. . . . CapeTown29_24M_2010_06_08 (
. . . . . . . . 34D,
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F,
. . . . . . . . 275I,
. . . . . . . . syn287G,
. . . . . . . . syn305K,
. . . . . . . . syn346G,
. . . . . . . . 382I [NY2372_2010_01_20
. . . . . . . . . . . . . . . . . with 128D, 233H, 273A, syn283Q,
. . . . . . . . . . . . NewZealandWaikato2_2010_01_04
. . . . . . . . . . . . . . . . . with 233H, syn283Q,
. . . . . . . . . . . . NY_INS317_2009_12_17
. . . . . . . . . . . . . . . . . with 233H, 273A, syn283Q,
. . . . . . . . . . . . Hawaii28_2009_10_10
. . . . . . . . . . . . . . . . . with 159D,
. . . . . . . . . . . . Cameroon357_2009_08_08
. . . . . . . . . . . . . . . . . with 225E])

Please refer to additional studies for further genetic analyses, including the survey on amino acid revisions potentially related to Vaccine Escape.  A hyper-morphic, TamiFlu-resistant sequence from the state of Washington in Spring 2010 has recently been profiled with similar zoonotic influences.

Previous Study on this Topic:

• 2010-08-07 HA Spreads Across US and Travels to the Ukraine Again
• 2010-09-27 225G Sequence from Pennsylvania Extends Sub-Clade with Fatality Markers from Russia and Brasil

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