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Paradigm Shift Intervention Monitoring
The Health Protection Agency
published a paper
on recent sequences from the current H1N1
outbreak, which included phylogenetic
analysis of 41 HA sequences. S188T was present in 21 of the
41 sequences, extending its worldwide expansion
and domination in England.
However, the sequences with S188T had additional evidence of recombination. One subset had acquired D100N, which was present on an earlier sequence and was also found on different genetic backgrounds outside of England.
Of great concern was two sequences, A/England/4880378/2010 and A/England/4940476/2010, which had D225G appended onto the background with S188T and D100N. D225G had previously been associated with severe and fatal cases in Ukraine and Russia, and to a lesser extent in many countries with sequences representing multiple genetic backgrounds, demonstrating expansion by recombination. In England both cases with D225G were severe. However, both sequences also were identical, signifying clonal expansion.
The paper did not explain the relationship between the two patients with D225G, but a clonal expansion is a concern. This concern is increased because both sequences contained S188T, which is dominant in England and is likely associated with immunological escape, as well as D100N, which is on multiple genetic backgrounds and also becoming increasingly common.
D225G hitchhiking on a dominant genetic background could lead to a significant increase in the polymorphism leading to more severe and fatal cases. Two of the five HA sequences from 1918 had D225G demonstrating the transmissibility of D225G under the appropriate circumstances.
In the upper branch of the tree with S188T and D100N, 5 of the 7 sequences are from severe or fatal cases, including the two with D225G. Detection of D225G is somewhat dependent on when and where the sample is collected. Thus, the level of D225G on this branch may be higher than the two cases noted.
This branch has two changes in or near the receptor binding domain, D225G and S188T, recombined with D100N, which is on at least two different genetic backgrounds in England, signaling more recombination.
The new combination raises serious concerns about an increased frequency in severe and fatal cases, as seen in England. More information on the two cases with D225G, as well as a release of all sequences used to create the published phylogenic trees would be useful.
Most publications require the deposit of such sequences in a public database so statements and conclusions in the paper can be independently evaluated and confirmed by the scientific community.