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D225E and D225N H1N1 RBD Changes in Turkey
Recombinomics Commentary 23:39
January 5, 2010

The Refik Saydam National Public Health Agency has released 29 HA sequences from Ankara, Turkey.  Several were partial sequences, but 26 covered the receptor binding domain and 8 had D225E (see list below), while one had D225N, A/Ankara/26/2009.  The outcomes of these patients were not given but media reports have described a rapid in increase in H1N1 fatalities in Turkey.  A large number of HA sequences with D225E has been published from Spain, and recently released GISAID sequences from Sweden and the UK also haveD225E, including three fatal cases from Sweden.  The prior reports of D225G and D225N associations with fatal cases has raised concerns that changes at position 225 could alter tissue tropism or aid in immune escape, leading to more severe and fatal cases.

In addition, the first reported cases of H274Y in an H1N1 patient who had not been treated with Tamiflu also had D225E as did another H274Y isolate from Tennessee, raising concerns that H274Y would pair up with receptor binding domain changes and become fixed, as happened with H274Y in seasonal H1N1.

In addition to the large number of isolates with D225E, the isolate with D225N has an additional marker that matches recent sequences from Russia and Denmark.  Two of the Russian isolates were fatal and those sequences had D225G.  The presence of D225G and D225N on similar backgrounds raises concerns that these isolates are mixtures, as seen in patients in Mexico, United States, and Sweden, where both D225G and D225N were present.

The presence of both sequences could lead to pseudo-types which use D225N to infect the upper respiratory tract and D225G to infect the lower respiratory tract.  The increasing presence in these changes at position 225 continue to raise concerns that these changes will lead to increased Tamiflu resistance, severe cases, and fatalities in the next pandemic H1N1 wave, which may begin in the next few weeks.


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