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Emergence of H1N1 Tamiflu Resistance on Clade 2C In China
Recombinomics Commentary 13:53
July 17, 2008

NA sequences being released at Genbank include two isolates from China with H274Y.  The isolates (A/Zhejiang/Xiangshan522/2006 and A/Gansu/Chenguan/1129/2007) were collected in the 2006/2007 season in August and January, and are related to A/Hong Kong/2652/2006, the prototype clade 2C sequence which is widely circulating in Asia.  All three of the above isolates, like the vast majority of clade 2C isolates, has M2 S31N, conferring amantadine resistance.

The presence of H274Y in China in clade 2C has not been reported previously.  Moreover, the upcoming paper “Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide in 2004-2008” indicated that these patients did not develop the resistance due to Tamiflu treatment.  In the 2006/2007 season, public sequences with H274Y were limited to New Caledonia, clade 1 in five isolates in the United States.  Four of these isolates were described in the above paper, and only one of the four had been treated with Tamiflu prior to sample collection.  In the 2007/2008 the incidence of H274Y exploded in the Brisbane/59 strain, clade 2B and almost all patients positive for H274Y had not been treated with Tamiflu prior to sample collection.

Thus, in the past two seasons, H274Y has been reported on clade 1, 2B, and 2C genetic backgrounds.  Moreover, phylogenetic analysis of clade B isolates indicates the H274Y was due to multiple independent introductions.

These independent introductions onto multiple genetic backgrounds which are clustered in time are similar to G743A introductions in H5N1 in early 2007 on a varient of clade 2.2 genetic backgrounds. 

These data are most easily explained by homologous recombination with a common source.

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