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H1N1 RBD Changes D225G and D225E in Norway
Recombinomics Commentary 17:39
November 24, 2009

Twenty-five HA sequences from Norway have been released at Genbank.  The isolates were collected between May and October and include six sequences with receptor binding domain changes.  All changes are at position 225, but 5 of the 6 have D225E, while the sixth has D225G as well as wild type D225.  Outcomes are not included in the characterization sheet, but it is not likely that the two fatal and one serious cases described in media releases last week were samples with D225E because the WHO briefing on Norway presented a country list that matched D225G reports.

D225E is not as well characterized as D225G, which was in 1918/1919 isolates and was characterized in receptor binding studies which demonstrated that D225G targeted alpha 2,3 receptors, like those in lung, as well as alpha 2,6 receptors. D225G was also found in four of four fatal cases in Ukraine.

The finding of D225G in Norway (A/Norway/2924/2009) as a mixture with wild type sequences confirms that isolates with receptor binding domain changes can be circulating as mixtures and the sequence identified will be dependent on the tissue sampled and when it is sampled.  Thus, Infections with a high frequency of D225G will likely be quickly cleared from the upper respiratory tract because viruses with D225G will quickly go to the lungs, which wild type sequences will be more quickly cleared from the upper respiratory tract. Thus a nasopharyngeal swab may be negative if all not cleared virus has moved to the lungs, or be positive for the wild type if depleted wild type H1N1 is remaining at the time of swabbing.  Thus, the true level of D225G may be grossly under estimated by nasopharyngeal swabs, and the one sample positive for D225G may reflect the rare instances where D225G could still be detected in a nasopharyngeal swab.

These recent sequences provide additional data for widespread isolates with receptor binding domain changes at position 225, but the true distribution may require sampling more representative of virus that has infected the lower respiratory tract, including lung.

gb|CY052015.1 A/Norway/4023/2009
gb|CY052007.1 A/Norway/3478/2009
gb|CY051991.1 A/Norway/3059/2009
gb|CY051987.1 A/Norway/2690/2009
gb|CY051986.1 A/Norway/2674/2009

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