H5N1 Coding from 2009 Egypt Toddler Cases enters PF11 Reservoir via Japan, NA 450G

A/Shizuoka/793 was deposited yesterday at GenBank with Segment 4 (HA) and Segment 6 (NA) from a sample taken 2009-06-15.

Influenza Flux is at work demonstrating increasing Antigenic Diversity.  The Japanese geography continues to produce genetically diverse PF11 strains with two significantly variant sub-clades represented in the two sequences deposited yesterday from the Shizuoka Prefecture. 

Shizuoka793 is unique within ΣPF11 for several reasons.  Though the Neuraminidase gene segment is identical at 1408 of 1410 residues to most recent geographically proximal Japan sequences and many NY specimens, the two exceptions provide us an exercise in origins:

  • A1028C coding for A343E (Glutamate) 
  • G1348A coding for S450G (Glycine)
Neither of these polymorphisms appear to have precedent within ΣPF11 and, as yet, we have not identified a donor candidate within the H1N1, H3N2, H1N2, H5N1 or H5N2 reservoirs for the NA:343E.  450G, on the other hand, has a lineage that is of interest considering the risk groups that we are seeing at the moment with this pandemic.

450G found on the pandemic Shizuoka793 in mid-June appears in low density among several serotypes of human Influenza specimens worldwide at GenBank and 18 are H5N1 specimens collected and sequenced by the NAMRU-3 team in Egypt between January and June 2009, immediately prior to the Shizuoka infection.  16 of those patients were under the age of 5 and geographically dispersed

Other recent matches are 7 H3N2 Seasonal 2009 cases, 17 H3N2 Seasonal 2008 cases, 5 H1N1 Seasonal 2008 cases, 13 H1N1 Seasonal 2007 cases, 11 H1N1 Seasonal 2006 cases and a swine farm worker from Iowa in 2005.  Though the Glycine at 450 is an uncommon Human Influenza polymorphism, the coding appears to be easily donated, moving between Avian, Swine and Human species on H5N1, H3N2 and H1N1 serotypes.  Clinical data on the Shizuoka case and the H5N1 infected toddlers would allow valuable insight.

The Neuraminidase Quadruple Combination on this sequence is 106I, 248D, 275H, 286S.

The Shizuoka793 Hemagglutinin is a perfect match (1701/1701) to 22 PF11 specimens from geographies including Sao Paulo, Finland, Italy and 18 specimens along the US Eastern Seaboard.  The HA 296H polymorphism deepens in Japan with this deposit being only the second in Japan, the eighth in Asia and the fifty-first in the world.  The sub-clades bearing 296H do not appear to have become dominant in any single geography, but have, nonetheless, continued alongside the dominant strains.  As of this moment, the Intra-Segment Exclusivity between 296H and 206T continues within ΣPF11 though 206T is widely circulating proximally to this specimen.

Cross-segment linking is suggested with all HA:296H specimens sharing the NA combination of 106I, 248D, 275H, 286S (for those 44 with NA on record).  No specimen bearing HA:296H is on record as TamiFlu Resistant or as carrying the NA:286G from Seasonal Influenza (H1N1/H3N2) or H5N1.

This specimen also demonstrates the strong pairing between 296H and the 2E originally found in 1918 sequences and now several PF11 HA segments.

We would be very happy to report that sub-clades are coalescing and stability is occurring within ΣPF11, but the data does not support such a view.  Even casual observation of the sparsely available sequences shows ongoing genetic acquisition leading to Antigenic Diversity and widening sub-clades.  Reversion and flux appear.

Tracking of these non-random linkings would certainly be assisted by a more robust database of recent sequences.

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