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Commentary

H1N1 Low Reactor G158E In Athens Greece
Recombinomics Commentary 11:13
March 10, 2010

Recently released sequences from Mill Hill at GISAID included a sequence, A/Athens/16606/2009, from Greece collected on December 26, 2009.  The sequence contained G158E, which was found in low reactors designated by Mill Hill and the CDC.  Although only a partial sequence was released, it contained E377K, which was also in the Hyogo/1597/2009 isolate from Japan, indicating G158E was transmitting.  Similarly, four of the G158E sequences from Japan also had A200T including one sample with H274Y.  Another sample in Japan had D225N, while samples in Italy and Russia had D225G.

These various combinations signal movement of G158E from genetic background via recombination, which was also seen for D225G, D225N, and H274Y.  D225G has also been designated a low reactor marker, leading to concerns that these markers will be more common in upcoming waves, including the wave which may be beginning now.

Increases in these markers would lead to more severe and fatal cases as indicated by the association of D2225G/N in Ukraine, Norway, and Greece.  Although current approaches has yielded high frequencies of D225G, the detection of D225G in egg isolates from mild cases raises concerns that low levels of D225G may be widespread, and increases may be missed with current assays which focus on direct sequencing and growth of virus in mammalian cells, which failed to identify D225G in milder cases, which had D225G in egg isolates.  However, this failure may be linked to mixtures in these samples, which may be less common as immune responses reduce the level of wild type receptor binding domains.

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