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D225E and D225N H1N1
RBD Changes in Turkey
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.