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HA 230I RBS Polymorphism Potential for Europe

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  • HA 230I RBS Polymorphism Potential for Europe

    2010-08-31

    HA 230I RBS Polymorphism Potential for Europe


    Current trending indicates a reportable potential for the M230I polymorphism spreading on the Hemagglutinin of PF11. This Receptor Binding Domain change may enhance Vaccine Escape from the currently selected vaccine target candidate, CA/07 X181.

    For those who are following the prediction on February 25, 2010, the pandemic reservoir now shows multiple instances of multiple encodings for 230I. Model adjustment and data transparency allowed a second set of detailed geographic predictions on 2010-08-09 that have also found traction.

    The 230I bearing sequences meeting the prediction are documented in the detailed discussion on Vaccine Escape that demonstrates a 100% change rate in the pandemic influenza (pH1N1) reservoir at the critical HA genetics range between amino acid positions 186 and 248. 87% of the amino acid positions have notated revisions.

    Expectations for the M230I polymorphism, that first came to our notice for zoonotic concern on the H5N1 human fatality cluster, have now been revised based on the most current public data. The GeneWurx model approximates that HA 230I will appear in the PF11 RBS according to the following geographic probabilities.

    • 75% probability in Germany sampled by 2010-12-01.
    • 75% probability in Spain sampled by 2010-12-01.
    • 85% probability sampled by 2010-12-01 in one of:
      • Denmark
      • Norway
      • Sweden
    • 5% or less probability of HA 230I within 60 days of conserving across PF11.
    • 7% probability of HA 230I within 180 days of conserving on one or more Hydrae.

    This HA polymorphism guided an investigation suggesting that anti-viral resistance from the NA H275Y revision is not the only genetic concern with over-usage. Anti-viral drug usage may drive 230I genetic acquisition, with a higher potential among children and young adults (0-24 years old). The sparsity of complete sequences, discounted by the lack of required meta-data, allows only a rough postulation on the mechanism.

    An accelerated viral self-revision, subsequently moving toward M230I, may be modulated by the substantially higher rates of host exposure in the lower age brackets. Additionally, that group?s multiplicity of exposure to a wider variation of influenza strains may factor into the host response/viral revision equation. In plain terms, the viral reservoir is being forced toward hard labour in order to infect and re-infect the youth.

    Just as hard work builds muscle, viral exertion against a complex host response challenges the reservoir subset to revise toward an optimal solution. 230I is an excellent and proven tertiary response for a virus on this type of offensive.

    These probabilities will be updated as additional data is made public. Transparency at this post-pandemic stage is essential to formulate viable responses for the risk groups. Release of sequences and clinical data of a finer detail and higher quantity will allow information-based decisions.



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

  • #2
    Re: HA 230I RBS Polymorphism Potential for Europe

    On August 31, 2010, GeneWurx predicted potential for HA 230I in Europe to appear in samples taken by 2010-12-01. Sweden was discussed in a group with Denmark and Norway as having an 85% potential to demonstrate HA 230I within that sample period.

    Then the Western world cut sequence publication to a trickle. Only 13 pH1N1 HA sequences since then have come from Sweden. On 2011-02-04, The Swedish Institute for Infectious Disease Control published 3 sequences at GISAID.

    One in that subset today, sampled from a 23 year old female on 2010-12-21, carries the HA 230I. Though the sample does post-date our prediction by 20 days, we would suggest that if full publication of the internal databases were to occur, we’d see several 230I sequences as early as October 2010 . . . well within the prediction window.

    Withholding data does nothing to invalidate these predictions which have a sample time deadline. Data currency is essential to solving these world health crisis puzzles, but we are willing to wait for corroboration if it takes 50 years to publish 4 month old data.

    The 230I sequences are also likely to be circulating in the United States as well, as is evidenced by the ignition markers found in the most recent GISAID US publications of the past two weeks.

    This 230I from Sweden, SwedenHalmstad1_23F_2010_12_21, patterns with rare 230I sequences on certain polymorphisms (syn245F, 280A), but then demonstrates extensive homology with the most recent 188T sequences (100N, syn338G, 377K, 454N, 537S), including the fatal UKEngland5040499_2010_12_f.

    HA 230I appears to be a jumping polymorphism now and has landed on the most dominant sub-clade in publication (may be biased against actual circulation) around the entire world. The 188T backbone is now demonstrated as permissive to receiving 230I as a tertiary Immune Escape feature.

    The SwedenHalmstad1_23F_2010_12_21 sequence falls on a phylogenetic tree branch with one other 188T Swedish sequence from this publication, SwedenVaxjo2_37F_2010_12_22, and 4 contemporary Australian sequences also published this week from Darwin, Sydney and Victoria (2). HA 230I may become popular as a 2011 pH1N1 tertiary Immune Escape feature if these patterns continue.

    A 159K change in the HA amino acid range of 156 to 159 (generally associated with Vaccine Escape) is also found on this hybrid virus. The syn245F is also found on a Russian 230I sequence with domaining homology at 158E, 225G, 230I & syn343G. The 280A is found on a 2010 TamiFlu Resistant sequence and may be an HA signal relating to potential for TmX. At any rate, the 280A is conserved in swine with domaining homology at 156E, 225N, 230I & syn346G.

    GeneWurx_UK_December_Emerging_Genetics_v5.xls

    . . . . SwedenHalmstad1_23F_2010_12_21 (
    . . . . . . . . 100N [Slovakia1625_56X_2010_03_30_xL
    . . . . . . . . . . . . . . . . . . . . with 230I],
    . . . . . . . . 159K [UKEngland4940476_2010_08
    . . . . . . . . . . . . . . . . . . . . with 128D, 377K,
    . . . . . . . . . . . . . NY3230_2010_01_25
    . . . . . . . . . . . . . . . . . . . . with 100N, syn231N],
    . . . . . . . . 188T,
    . . . . . . . . 230I,
    . . . . . . . . syn245F [RussiaBelgorod2_2010_03_15
    . . . . . . . . . . . . . . . . . . . . with 158E, 225G, 230I & syn343G],
    . . . . . . . . 280A [MXinDRE797_2010_TmX
    . . . . . . . . . . . . . swIowa44837_1_2009_11_08_xL
    . . . . . . . . . . . . . . . . . . . . with 156E, 225N, 230I & syn346G],
    . . . . . . . . syn338G,
    . . . . . . . . 377K,
    . . . . . . . . 454N,
    . . . . . . . . syn537S [UKEngland5040499_2010_12_f])
    Last edited by NS1; February 5, 2011, 06:45 AM. Reason: format

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