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Fit Hong Kong Tamiflu Resistant H1N1 Is a Mixture
Recombinomics Commentary 19:54
December 1, 2009

Estimation of 274H and 274Y populations in the NPA specimen was performed by cloning and sequencing PCR products. The NPA specimen contained approximately equal proportions of 274Y and 274H (52.63% and 47.37%, respectively).

The above comments are from an upcoming EID paper on the swine H1N1 with H274Y isolated in Hong Kong from a San Francisco traveler. Since the patient was not taking Tamiflu, the detection of H274Y was an example of an evolutionarily fit H1N1 with H274Y.  However, the paper indicates that the sequence was from the virus passaged in MDCK cells and the sequence had a minor peak representing the wild type sequence.  The above quote describes the result of cloning from the original samples, which indicated the two populations were present in proportions that were almost equal.

The detection of H274Y in a San Francisco traveler who had not received anti-viral treatment led to a survey of samples in California which failed to detect H274Y.  However, earlier and subsequent data strongly suggested that H274Y was circulating as a mixture because brief treatment with prophylactic or therapeutic Tamiflu led to frequent detection of H274Y.

The transmission of evolutionarily fit H274Y was further supported by the recent release of multiple sequences with H274Y at GISAID by the CDC.  One of the isolates, A/Tennessee/17/2009 has HA and NA markers which match the Hong Kong ex-San Francisco sequence strongly suggesting that this sub-clade with H274Y is transmitting in the United States.

The transmission of swine H1N1 with h274Y allows for the jumping of one genetic background to another via homologous recombination, as was seen for H274Y in seasonal H1N1.  The recent clusters of H274Y in Wales, Scotland, and two outbreaks in North Carolina, suggest that examples of H274Y on various swine H1N1 genetic backgrounds will become increasingly common and will likely lead to fixing in swine H1N1 as happened for seasonal H1N1.

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