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H1N1 D225G D225N D225A in Ukraine Lungs
Recombinomics Commentary 23:39
January 8, 2010

Mill Hill has released a series of H1N1 European sequences at GISAID. Included was a series from Ukraine collected in November.  Sequences from Lviv in western Ukraine were from swabs, and were likely from recovered cases.  These cases matched the sub-clade seen at Lviv in October collections.  The outbreak moved to the east in November, and two isolates from Kyiv and the adjacent Chernihiv oblast were from lung washes (A/Kyiv/377/2009 and A/Chernihiv/452/2009).  Both lung HA sequence had mixtures of receptor binding domain changes at position 225.

Earlier, Mill Hill had released nine HA sequences from western Ukraine (see map). Five were nasal washes and were a closely related sequence from Ternobil and Khmelnitsky had a wild type receptor binding domain.  In contrast, four were lung or throat samples from fatal cases, and all four had D225G.  The CDC subsequently released five sequences.  Three were from three Ternobil sequences, but two were unique and were likely from additional fatal cases.  Both of these sequences had D225N.  Others, including recent reports from Russia, had reported D225N and D225G from the same location or the same sample.  Both polymnorphisms from the same sample had been seen in Utah in the United States, San Luis Potosi in Mexico, and Stockholm in Sweden.

The two Ukraine lung sample also has mixed signal at position one and two in codon 225, encoding both D225G and D225N.  However, the sample from Kyiv also had a third signal at position two of codon 225, encoding D225A, which has been seen previously in swine from Northern Ireland in 1938.

This added complexity at position 225 raises concerns that the H1N1 in Ukraine is rapidly evolving away from the initial immune response, which is leading to a higher frequency of position 225 changes, which are associated with more severe cases. 

The changes have now been found in at four location in Ukraine (Lviv, Ternopil, Kyiv, and Chernihiv) from eight patients.  It is likely that all eight infections were fatal. Lung samples had been tested from at least five of the patients and all lung samples had D225G, D255N, or both.  One sample also had D225A. 

The presence of three newly acquired polymorphisms at the same position in one patient is a strong signal of immunological escape, leading to a fatal outcome.

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