Recombinomics Commentary 16:05
December 21, 2009
As the number of H274Y cases continue to expand, the transmission of these cases comes into sharper focus.  The recently released sequences from Japan, which include eight sequences with H274Y defines a number of sub-clades with multiple examples of H274Y, signaling the transmission of H274Y.

One example involves sequences which have H274Y and D225E,  This combination of Tamiflu resistance with a receptor binding domain change is of concern because prior fixing of Adamantane resistance, S31N, in seasonal H3N2, and Tamiflu resistance in seasonal H1N1 involved receptor binding domain changes.  In H3N2 the two key RBD drivers were S193F and D225N.  In seasonal H1N1 it was A193T followed by changes in flanking positions 187, 189, and 196.

Thus, when the first example, A/Hong Kong/2369/2009,  of H274Y in a patient (San Francisco traveler to Hong Kong) who had no documented exposure to Tamiflu, had D225E, there was concern that this change would lead to more examples of this combination.  The report led to increased surveillance in northern California, which failed to pick up additional examples ofH274Y or D225E.  However, other countries screening passengers at border checks identified sequences with D225E, and most were passengers from the United States raising concerns that the US surveillance was missing milder cases with D225E, because most testing was directed at hospitalized patients.


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