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Hong Kong Tamiflu Resistant Pandemic Sequence Released
Recombinomics Commentary 06:57
July 7, 2009

The NA sequence from the Hong Kong teenager with oseltamivir  Tamiflu resistance, A/Hong Kong/2369/2009, has been released.  The sequence is clearly that of pandemic H1N1 and exactly matches (other than H274Y) the sequence of an earlier isolate A/New Jersey/1/2009.  Similarly, the HA sequence is also swine and has two recently acquired polymorphisms, one of which is also in New Jersey/1/2009.  Thus this sequence is in circulation and as was seen in the isolates in Denmark and Japan, the H274Y is appended onto a swine H1N1 background.

These results mimic that seen in seasonal flu, where H274Y was appended onto multiple seasonal flu background.  The polymorphisms jumped from one background to the next, via genetic hitchhiking and recombination.  Thus like seasonal flu, the pandemic H1N1 has no evidence of reassortment.  The H274Y is on an evolutionarily fit H1N1 that will allow the H274Y to move about through the pandemic H1N1 gene pool.  This movement will be facilitated by widespread Tamiflu usage, which will select minor populations as happened in Denmark and Japan, where H274Y was identified in patients receiving a maintenance dose of Tamiflu.

However, in Hong Kong, like the many examples of H274Y in H1N1 seasonal flu, the resistance is in patients not receiving Tamiflu.  However, the lessons of H274Y in seasonal flu were not learned.  Recent comments have described H274Y acquisitions through random mutation and reassortment.  However, there has been no examples of recent seasonal H1N1 flu genes in the pandemic H1N1 sequences, and the H274Y in patients receiving Tamiflu likely represent selection of a minor population with H274Y that is silently spread.  The release of the sequences from Denmark and Japan would be useful.

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