H5N1 and 1918 Receptor Binding Domain Change, HA 225G, Emerges On Two Sub-Clades in Spain

Spain deposited 239 sequences today at GenBank.

A/Catalonia/NS1706, sampled on 2009-07-29, Segment 4 (HA) and Segment 6 (NA)
A/Catalonia/NS2001, sampled on 2009-08-03, Segment 4 (HA) and Segment 6 (NA)
A/Catalonia/NS2008, sampled on 2009-08-03, Segment 4 (HA) and Segment 6 (NA)

225G is found on these 3 Spanish Hemagglutinins as in the 2 Sao Paulo cases during the same late July to early August timeframe.  On the CatNS1706 specimen, 206S is paired with the 225G; whereas, the Brasilian deaths were 206T and 225G similar to CatNS2001 and CatNS2008.  During the same timeframe, two cities more than 5,000 miles distant with an ocean between them each have emergence of multiple novel sub-clades for their geography related to the Receptor Binding Domain residue 225.  Consider seasonality and your puzzlement is enhanced.

225G is consensus for H5N1, is carried on NewYork1918 and only appears in 8 other PF11 sequences across the US and Mexico.


225X is demonstrated several times in the US proximal to 225G in area and time.


CatNS2001 and CatNS2008 also feature HA 298V, a potential reversion to swine sequences or to 2008 Seasonal.  Because 206T is featured in these two sequences and 206T is exclusive of 296H, we may perhaps postulate a secondary acquisition pathway for an unidentified human-fit, trait-enhancing domain (HA296:301)

Three additional sequences in this deposit carry the pair of 206T and 298V:
All 5 of these Catalonia 298V specimens carry a 225 polymorphism, either 225E or 225G.

An Intra-Segment Exclusivity exists within the Catalonia specimens between 206S and 225E.  24 of 25 Catalonia 225E specimens carry 206T, all but the unusual CatS1161 with 206A.

Neuraminidase Quadruple Combination

  • CatNS1706 = 106V, 248N, 275H, 286G 
  • CatNS2001 = 106I, 248D, 275H, 286S
  • CatNS2008 = 106I, 248D, 275H, 286S
  • CatNS1237 = 106I, 248D, 275H, 286S
  • CatNS1248 = 106I, 248D, 275H, 286S
  • CatNS1286 = 106I, 248D, 275H, 286S 
NA 286G appears on 30 GenBank specimens within ΣPF11, 24 of them from Catalonia. 

Non-Random Acquisition Acceleration appears to be underway in potential trait-enhancing domains of both Antigen segments.  Influenza Flux is a two way street with clearly defined lanes and many points of ingress.

The Hydra Effect is demonstrated in the phylogenic trees of Brasil and Spain.  When your tree is all branches with only a few leaves at each tip, you aren’t going to get much protection from the sun unless you decided very early to be standing on just the right spot when the perfect light of noon arrives.

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