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Commentary

Evolution of H1N1 Tamiflu Resistance in Japan
Recombinomics Commentary 18:37
November 18, 2008

in Tottori Prefecture during the 22 stocks in the 68-resistant strain, the frequency has been outstanding and 32.4 percent.

The above comments are from an updated Japan NIH report on Tamiflu resistance in Japan in the 2007/2008 season.  As noted above, the most concentrated Prefecture for H274Y was Tottori, where the rate was above 32% in H1N1 isolates.  The new report has an updated phylogenetic tree that demonstrates that H1N1 in Tottori included the dominant Brisbane sub-clade that accounted for the majority of H274Y cases in Europe and the United States, but also included isolates on branches that had isolate that did and did not have H274Y, indicating the H274Y positive isolates had independently acquired H274Y (see list below), supporting acquisition via homologous recombination.

As seen in the updated tree, the majority of cases reported in Japan were in isolates that were not on the dominant branch (shaded in pink), but were on multiple separate branches.

Similar data was seen in recent sequences released from England, where several of the H274Y isolates (England/654/2007 and England/684/2007) did not map on the branch with the dominant sub-clade, providing evidence for more independent acquisitions which are most easily explained by homologous recombination.  These multiple branches ion England and Japan offer additional clades which could become dominant this season.

Recent data from the southern hemisphere over the summer, and early isolates in the northern hemisphere this season, raise concerns that the resistance levels will approach 100% of H1N1 isolates in many countries.  Sequence data on isolates, including the US where H1N1 is the dominant serotype this season, would be useful.

Dominant Brisbane sub-clade

Okayama/11/08
Tottori/41/08
Tottori/42/08
Tottori/43/08
Tottori/44/08
Tottori/46/08
Tottori/50/08
Tottori/52/08
Tottori/53/08
Tottori/55/08
Tottori/56/08
Tottori/57/08
Tottori/59/08
Tottori/60/08
Tottori/67/08
Yokohama/77/08
Yokohama/78/08
Yokohama/79/08

Other branches

Branch 1
Yamagata/68/08

Branch 2
Shimane/59/08

Branch 3
Tochigi/34/08
Tochigi/39/08

Branch 4
Tottori/28/08
Tottori/29/08
Tottori/34/08
Tottori/35/08
Tottori/37/08
Tottori/63/08

Branch 5
Gifu-C/17/08
Gifu-C/38/08
Tottori/21/08
Tottori/23/08

Branch 6
Aichi/76/08
Kobe/27/08
Kobe/31/08
Kobe/32/08

Branch 7
Yokohama/22/08
Yokohama/30/08
Yokohama/31/08
Yokohama/34/08
Yokohama/35/08

Branch 8
Tochigi/8/08

Branch 9
Nagano/1100/08
Nagano/1107/08

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