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Commentary

Conversion of  H1N1 D225E to D225G in Rome Italy
Recombinomics Commentary 12:38
February 02, 2010

Fourty-one HA sequences have been released at Genbank from Istituto Superiore do Sanita in Rome, Italy.  Recently sequences from  Ancona and Pavia/Milan were released and those sequences had a frequency of D225E of 50% or higher in the absence of D225G.  In the series from Rome, 8 of the 41 sequences had D225E and two had D225G (A/Roma/ISS1941/2009 and A/Roma/ISS1897/2009).  However, the D225G sequences had the T717A change which codes for D225E, as well as C940T associated with D225E sequences, indicating both D225E sequences was converted to D225G.  One sample was collected on Aug 25 and the other on Oct 30.  A similar result was seen in Japan on a Dec 1 collection, although the signal for D225A (A716G) was mixed.  Earlier results from Norway, Sweden, and Spain have had similar conversions of D225E genetic backgrounds to D225G.

This type of conversion of D225E or wild type H1N1 to D225G or D225N has raised concerns.  The examples in Europe demonstrate how the acquisition of D225E can rapidly spread.  In addition to the high frequencies in Spain and Italy, recently released sequences from the UK also have a high incidence of D225E, which is the most common change at position 225.

However, in Ukraine, position 225 changes were dominated by D225G or D225N.  There was one example of D225A, which has also been detected in California, but no instances of D225E.  This dominance which is clustered in time and space and on phylogenetically similar sequences contradicts the ECDC report that D225G did not transmit, as well as the WHO report which maintained that D225G/N sequences did not cluster in time, space, or phylogeny. 

Moreover, the sequences from Ukraine had D225G and D255N on many different backgrounds, requiring multiple introductions. In addition, the same sequences with wild type or D225G, D225N or both D225G and D225N were present contradicting the claim that the position 225 changes were due to copy errors.  The copy error explanation is also contradicted by the frequencies of D225E in western European countries and D225G/N in eastern Europe.

These recently released sequences add to the compelling evidence that pandemic H1N1 receptor binding domain changes are being driven by homologous recombination, and strongly discount the WHO working hypothesis that these are random and spontaneous mutations that do not transmit.

The "random mutation" view of WHO and consultants continues to be hazardous to the world's health.

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