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D225G / D225N H1N1 in Case from Sweden
Recombinomics Commentary 23:54
December 28, 2009

The Swedish Institute for Infectious Disease Control has released a series of H1N1 sequences at GISAID.  Included was an isolate, A/Stockholm/92/2009, which has an HA sequences with mixed signal at adjacent codons allowing for the synthesis of D225G and D225N.  The same chnages were reported previously for a fatal case in Utah, A/Utah/42/2009, as well as two fatal cases (25M and 40M) in San Luis Potosi, A/Mexico/InDRE50625/2009 and A/Mexico/InDRE50617/2009) which were collected a day apart.  The same mixture was also in a swine sequence, A/swine/4/Mexico/2009 in the adjacent province, Quertaro.

The outcome of the infection in Sweden is unclear, but the patient was on ECMO, indicating it was a severe case.  Thus, all 4 cases with the tandem polymorphisms are from fatal or severe cases, even though the markers are on different H1N1 backgrounds.

This movement of adjacent changes from one background to another is most easily explained by recombination, which is also seen for the individual changes.  The same jumping from one genetic background to another was also seen for H274Y in seasonal as well as pandemic H1N1.

The appearance of these tandem polymorphisms as mixed signals on multiple genetic backgrounds may signal an advantage for having wild type as well as the polymorphisms encoding D225G and D225N in the same cells.  Alternatively, the mixed signals may signal D225S, although the changes in the absence of the wild type sequence have not been reported.  D225S would represent stronger evidence for recombination leading to acquisition of both sequences through one cross over event.

The increased frequency of these changes and strong association with fatal or severe cases raises concerns for this combination becoming more frequent.  These sequences were from a nasopharygeal swab, which is the most common source for sequences.

Thus, although the tandem changes remain rare, the increasing frequency raises concerns that such combinations could be catastrophic.

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