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Commentary
New Ukraine H1N1
Sequences Raise Concerns
Recombinomics
Commentary 19:05
January 13, 2010
The sequences were similar to the nasal wash sequences released earlier. Only one sample, A/Dnipropetrovsk/273?2009, had D225G (as a mixture with wild type), and were the same sub-clade seen in western Ukraine, bases on HA and NA markers. The HA marker that was limited to Ternopil and Khmelmitski isolates in the earlier collections was found on a subset of Dnipropetrovsk and Cherkasy isolates. The marker on one Ternopil isolate that was shared with New York isolates with D225N was also present in one of the Dnipropetrovsk sequences.
Thus, the new sequences indicated that same sub-clade was circulating throughout Ukraine, while regional markers within the sub-clade were present across a wide area in Ukraine. However, in fatal cases D225G, D225N, or both markers were appended onto this background, and the background had some region specific variation, consistent with acquisition by homologous recombination.
It was the movement from background to background that was the foundation for the prediction that fatal cases in Ukraine would have D225G/N. The newly released sequences support that mechanism because the RBD changes appear on multiple backgrounds at the same time as reported for changes in H5N1 as well as seasonal H1N1. This same pattern seen previously is being repeated for pandemic H1N1 leading to H274Y appearing on multiple genetic backgrounds as well as position 225 changes in HA also jumping from background to background.
Thus far the D225G and D225N acquisitions have been relatively rare. Recently released sequences had the first example of D225G in India as well as D225N in Japan. Similarly, the additional examples in Ukraine and Moldova which include both changes in the same samples significantly reduces the likelihood that these changes are due to independent random events which do not transmit, which is the current WHO working hypothesis.
Instead the appearance of the same change on multiple backgrounds at the same time is more easily explained by recombination. The increasing detection of these changes raise concerns that an increased frequency will lead to increased frequencies of severe and fatal cases.
The recent fatal cluster in Romania increases concerns that such cluster will become more common.
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