Russian Sequences, Omsk01 & Ekaterinburg01, show 2nd unique Quadruple Cross-Segment Combination (QC2)

Two of the sequences released by Russia's Vector lab in the past 7 days demonstrate another unique Cross-Segment Quadruple Combination (QC2) very similar to the combination (QC1) recently noted in the discussion on the Vector released Kazakhstani entry, Almati01.

Please review the sequences from the two samples for validation of this finding.

• HA / NA : A/Omsk/01/2009
• HA / NA : A/Ekaterinburg/01/2009

This introduction on the PF11 background carries a quadruple set of amino acids crossing Hemagglutinin and Neuraminidase:

        QC2

• HA 206T
• HA 226R
• NA 106I
• NA 248N

Omsk01 also carries NA:127S matching a polymorphic position with TamiFlu resistant Washington28.  Ekaterinburg01 shows NA:259D that appears unique at this time within ΣPF11.  Initial studies indicated that reassortment is impeached as a mechanism for these genetic acquisitions.

The QC2 changes, of course, are not fixed in the geography, as other sequences from the areas demonstrate considerable variation.  Movement within and around the Receptor Binding Domain (RBD) continues to draw our focus.

A University of Wisconsin-Madison study in 2008 found that Glutamine (Q) at 226 mediates the Binding Affinity for SAα2,6Gal (Sialic Acid α2,6) and, in turn, lowers infectivity levels in primary epithelial cells for humans compared to Leucine at that position (226L).  I am not aware of conclusive studies comparing 226Q to 226R in this regard.  Please contact me if you have applicable studies.

226R on PF11 Background (9)

• Omsk01
• Irkutsk02
• Ekater01
• Finland553 with HA:206T and NA:106I
• Lishui01
• ZhejiangDTID-ZJU01
• Texas17
• MX4603
• MXInDRE4487

Mixed signals or absent data for residue 226 appear in 13 ΣPF11 sequences across the US and Mexico.

At any rate, ΣPF11 in Eurasia and the Americas is now varying away from a stable, low infectivity position in the Receptor Binding Domain to an amino acid found in H5N1 at 226 (A/Anhui/2/2005/H5N1).  And I remind you that Anhui2 carries 206T and 296H which we are seeing persistently emerge throughout the world including clustering in Italy and the Northeastern United States.

Scrutiny is required here.

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