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D225G Ukraine Norway Link and China Spread
Recombinomics Commentary 14:15
November 25, 2009

The same mutation has been found in both fatal and mild cases elsewhere, including in Brazil, Japan, Mexico, Ukraine, and the United States, said the WHO.

WHO's spokeswoman in Beijing, Vivian Tan, said the agency is aware of three such cases in China that occurred in June and July that were similar to the cases being investigated in Norway. Tan said WHO had no information on the cases mentioned in the Xinhua report Wednesday.
There is no evidence the mutated swine flu virus is circulating widely in the world, Tan said, but since it has been linked to deaths in Norway and elsewhere, investigators are focusing on whether this mutation could be a marker for more severe disease.

The above comments are associated with a report of eight D225G isolates with in China.  Genbank has three of the sequences, as noted earlier.  The increase in examples to eight is not surprising since D225G was in four of four fatal cases in Ukraine and reports from Norway cited detection in three isolates, 2 fatal and 1 severe case who had recovered.

However, 25 HA sequences deposited at Genbank had an HA sequence that contained D225G, A/Norway/2924/2009,  but also had the wild type sequence, raising concerns that D225G was circulating as a mixture that was most easily detected in lung samples, because the D225G was more than a "marker".  It is a polymorphisms that was found in 1918 and 1919 samples which were well characterized for receptor binding properties, which indicated the change conferred increased binding to gal 2,3 receptors which are present in lung.

Concerns that this receptor binding domain change was widely circulating were increased because an HA marker on the Norway isolate with D225G was found on additional isolates in Norway, and worldwide (see list here).  This marker was also in the HA sequences from the fatal cases in Ukraine.  Full sequences from one of the Norway isolates, A/Norway/3364-2/2009, were deposited, and a marker on the NA sequence matched isolates with the HA marker, linking this broader set of isolate from Norway with the Ukraine sequences, which also had the NA marker, as did multiple other isolates (see list here).

These associations link Ukraine to Norway, but the D225G polymorphism has jumped onto multiple genetic backgrounds, which are widespread, increasing concerns the D225G is circulating undetected because it is concentrated in lung tissues and is poorly represented in nasopharyngeal swabs.

Release of full sequences from China, as well as Norway, would be useful.

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