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D225G and D225N In Utah Patient Raises Pandemic Concerns
Recombinomics Commentary 23:55
December 6, 2009

The CDC has put HA sequences, A/Utah/42/2009, from a Utah patient (28F) on deposit at GISAID, which has D225G and D225N.  Moreover, the sequence from the original sample gives mixed signals at tandem positions, revealing significant heterogeneity that the codon.  A clone for the original sample has D225GD225N and D225G have been identified in necropsy lung samples from Brazil (A Sao Paulo/53845/2009 and A/Sao Paulo/53838/2009 have D225N while A/Sao Paulo/53225/2009 and A/Sao Paulo/53206/2009 have D225G) raising concerns that these polymorphisms are associated with more severe disease.

The severity may be linked to viral load, because D225G and D225N were present as mixtures in early cases in the US in California and Texas. In fact the vaccine target, A/California/7/2009 was a mixture for D225G, as were several other isolates isolated at about the same time in Texas and California.  Other isolates in the same areas, as well as New York, did not give mixed signals, but D225G was found in milder cases.

More recently, these changes were found in more severe cases.  All four fatal cases in Ukraine had D225G, while the first fatal cases in Norway had D225G and D225E SNPs.  The Utah case above however is the first sample with D225G and D225N.  In the United States, the two isolates in New York with D225N had an additional polymorphism which was also in A/Ternopil/N11/2009, a fatal case from Ukraine, suggesting additional relationships which are not well represented in the existing database.  These relationships may be obscure because of tissue specific expression, and mixtures which are impacted by cloning procedures.

However, the recent findings sequences encoding D225N and D225G, as well as wild type, in the same sample raises concerns that this diversity has paved the way for rapid and varied responses to immunological pressures which has already cause concerns due to the low reactor status of D225G when tested against anti-sera directed against the target of the killed vaccine.

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