H1N1 Tamiflu Resistance Linked to Brisbane Subclades
Recombinomics Commentary 12:20
April 21, 2008
Recently released NA H1N1 sequences with Tamiflu (oseltamivir) resistance marker H274Y have focused attention on the Brisbane/59 strain. In the United States, H274Y was reported on the New Caledonia strain last season, but this season all isolates with H274Y have been the Brisbane strain, even though 76% of the H1N1 isolates in the United States has been the Solomon Island strain. Thus, although the frequency of H274Y is only 10% in the United States, the frequency in public N1 sequences is 29%, which is close to the level in several European countries. Thus, countries with low frequencies of the Brisbane strain may have a low frequency of H274Y.
However, H274Y is only present in a subset of Brisbane isolates and recent data released by Italy, indicates the low level H274Y (< 1%), is linked to an absence of the Brisbane sub-clade with H274Y. A phylogenetic tree of 2008 isolates in Italy signals a high frequency of the Brisbane strain.
Recent sequence data from England and Turkey further supported a specific Brisbane subclade. In the United States, H274Y is found on two Brisbane branches. The smaller branch, composed of isolates from western states, has two H274Y positive isolates from Hawaii. The larger branch however, has isolates found through the lower continental states. The sequences from England and Turkey exactly match US isolates on this branch. Thus, this branch includes isolates from a large geographical region in the United States and Europe.
The widespread detection of this Brisbane sub-clade indicates it is evolutionarily fit and was created after the Brisbane sub-clade formed. Similarly, the small branch signals a second introduction of H274Y in the Brisbane strain.
More sequence data from H274Y positive isolates will determine the number of independent introductions, which point toward acquisition from a common source.
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