225G in Receptor Binding Domain Traveled to China without Vaccine Pairing of 206S

The expected Hydra Effect on Hemagglutinin patterns are being validated with the latest sequence deposits.  Multiple antigenic heads continue to arise within single geographic areas while the march from Southern Hemisphere winter strains (May-July 2009) into the Northern Hemisphere ΣPF11 lays distinct markers.

Two sequences today from China carry the Receptor Binding Domain polymorphism coding for 225G similar to the fatal cases during the South American winter.  These sequences represent the first movement of 225G into China and the second into Asia after Hiroshima201, although we have observed 225E in one instance, Changsha78.

This incursion of 225G makes Zhejiang Province one of very few geographic locales to represent both vaccine RBD polymorphisms as 226R was demonstrated mid-summer in A/Zhejiang/DTID-ZJU01/2009.

Let's examine the new Yiwu HA segments for this analysis:

• A/Zhejiang-Yiwu/11/2009     
• A/Zhejiang/DTID-ZJU02/2009  

These two Zhejiang province cases were sampled in September making the sequences contemporary for evaluation of the genetic acquisition cycle pertinent to North America today.  Each case continues the recent affinity of 206T with 225G.  Nine of fourteen instances of 225G on record within ΣPF11 are paired with 206T and only one isolated sequence after April has 206S in the pairing. You will note that the live vaccine is based on an early finding in Texas and Mexico (Texas05 pairing of 206S / 225G).  The current sequences continue to demonstrate a directional movement away from those four early Texas and Mexican strains from April. 

The Yiwu11 case, 41F, is specifically noted as having "severe symptoms".  Confidence is increased that these sequences are valid due to independent verification.  The two sequences were managed from separate labs though the hosts were apparently from the same city, Yiwu, and suffered during the same time frame.

Each of the two HA sequences represent a novel introduction into ΣPF11.   Yiwu11's closest GenBank match is 1758 of 1774 nucleotides and ZJU02's closest match is Yiwu11.  The two sequences are an exact nucleotide match (1759/1759) at all alignable positions (sequence truncation at Yiwu11 head and ZJU02 tail), potentially representing perfect transmission in Asia of 225G.  The Catalonia sequences from Spain in early August initiated the first and only previously recorded perfect segment transmission of a 206T / 225G pairing.  The Brasil deaths share amino acid homology, but varied at a silent SNP coding for Lysine at residue 222 (222K). 

If a cluster is in effect with these two sequences, then we may be observing a foundational, well-passaged, human-fit strain in the Northern Hemisphere heralding Pandemic 2.0 Influenza.    Only time will tell.

A correlation is also emerging in consideration of geography and population ethnicity with nine of the fourteen 225G cases in areas with a substantial Hispanic population. The ethnic profiles of the individual cases are not identified. Yiwu is a burgeoning commodities trading area with a substantial immigrant population including import/export workers from South America.  If we note that NY and Georgia have Hispanic populations, then only Hiroshima remains as a potential non-Hispanic area.  At any rate, the correlation of 225G to areas with Hispanic human genotypes bears scrutiny for pathogen-host interaction at the genetic level. 

Recall that other human-fit genetic advances are recorded in the Zhejiang Province recently.  Of minor note, the Neuraminidase segments of Yiwu11 and ZJU02 are also novel to the reservoir though the amino acid levels match widely.  A third base SNP that merits attention has now spanned from the original introduction in A/Netherlands/602 to ZJU02, A408G coding at residue 136 for a synonymous Glutamine (136Q).  Movement at this amino acid position is implicated in Relenza resistence (136K), though the synonymous change from the Netherlands and Zhejiang is not accorded trait enhancement in the literature.

This advancing Antigenic Diversity and movement of 225G separated from the 206S into a highly populated country prior to winter should generate a call for wider surveillance and more rapid deposition of sequences.

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