H1N1 in the United States RaisesTamiflu Resistance Concerns
Recombinomics Commentary 23:55
November 07, 2008

The latest CDC report on influenza in the United States this season indicates that 80/112 isolates have been influenza A and 16/25 of the sub-typed influenza A was H1. These initial data points indicate a significant portion of influenza infections in the upcoming weeks will be H1, raising concerns of Tamiflu resistance.

Although reports from the US have yet to comment on H274Y levels this season, the first characterized isolate in Canada had H274Y as did the first three reported H1 cases in the UK. The UK and Canadian data raise concerns that resistance will be at or near 100% for H1 isolates.

The isolates in Canada and England were characterized as Brisbane/59 although it remains unclear if the analysis will discriminate between Brisbane/59 (clade 2B) and Hong Kong/2562 (clade 2C). Last season all clade 2 isolate were characterized as Solomon Island-like (clade 2A), although there were no reported Solomon Island isolates. In the US all clade 2 isolates were Brisbane or Hong Kong and Tamiflu resistance was limited to Brisbane, and the vast majority of resistance cases were limited to a clade 2B sub-clade, which was also the case in Canada and Europe.

Eventually, isolates were called Brisbane/59-like, but the change in terminology did not provide any discrimination between clade 2B and clade 2C, which were easily distinguished phylogenetically. These sub-clades were also easily distinguished serologically, if the target isolates were grown in mammalian cells. The anti-sera used produced extensive cross-reactivity when the virus was grown in chicken eggs, but Brisbane anti-sera had a titer of 320 with Brisbane, which dropped to 40 for Hong Kong and was below the limits of detection with Solomon Island (and New Caledonia). This large differential led to changing the H1 immunogen from Solomon Island to Bisbane this season, but the utility of the new vaccine may be limited.

Isolates from South Africa had acquired a number of changes near the receptor binding domain, and recent isolates from Hong Kong were clade 2C and had H274Y. Moreover, one of the clade 2C isolates had a clade 2B NA (acquired through reassortment), while one of the changes near the clade 2B receptor binding domain was from clade 2C (acquired through recombination).

Therefore release of HA and NA sequences from new isolates in the northern hemisphere would be useful.
http://www.recombinomics.com/News/11070801/H1N1_US.html