H1N1 Tamiflu Resistance Spread Through Southern Hemisphere
Recombinomics Commentary 13:26
September 24, 2008

The meeting reviewed the data and scientific findings gathered during the 2007-2008 influenza season in the Northern Hemisphere and new data from the Southern Hemisphere 2008 season.

The above comments are from a recent WHO meeting on oseltamivir (Tamiflu) resistance in H1N1 seasonal flu linked to H274Y.  The document includes NA and HA phylogenetic analysis of many of these recent isolates.  As seen in the NA tree, all isolates in the upper arm have H274Y.  This branch corresponds to the “Northern EU” branch released previously.  As can be seen in the recent tree, the isolates in this branch represent Tamiflu resistance at the beginning of this year in the northern hemisphere, as well as recent isolates from the southern hemisphere (see list below).  The earlier tree, which had many isolates from Japan, had a higher percentage of H274Y positive isolates that were not in the “Northern EU” branch (see second list below).

In the more recent tree, the majority of H274Y positive isolates form a distinct branch, which is also true for 2007/2008 public sequences from isolates in the United States, as well as isolates from Turkey, France, and South Africa (see third list below).  Thus, there is one dominant Brisbane/59 sub-clade, which has produced the majority of the reported H274Y isolates, but there are additional examples in each tree representing independent acquisition of H274Y.  These independent acquisitions may be linked to recombination with the dominant sub-clade.

This dominant sub-clade also gave rise to the dominant sub-clade in South Africa, which has a cluster of changes in the HA sequence near the receptor binding domain at position 190.  Two of the Seychelles isolates have these changes in HA, but are not markers as having H274Y.  One is listed in the NA tree, but it does not map with the South African sequences, suggesting it is a reassortant, or mislabeled.

In either event, the new phylogenetic trees show that the dominant H1N1 subclade is widespread in the northern and southern hemisphere, suggesting it will reappear in H1N1 infections in the upcoming season.

Aug-Dec 2007
Norway/1736/07
Paris/341/2007

Jan-Mar 2008
Athens/41/2008
Belgium/812/2008
Belgium/850/2008
Belgium/858/2008
Berlin/47/2008
Bucharest/229/2008
Buenos Aires/13/2008
Cameroon/25/2008
Estonia/6/2008
Finland/11/2008
Geneva/9296/2008
Hong Kong/852/2008
Ireland/744/2008
Kiev/313/2008
Lisbon/3/2008
Luxembourg/116/2008
Parma/34/2008
Slovenia/123/2008
St. Petersburgh/12/2008

Apr-Aug 2008
Cameroon/73/2008
Cameroon/80/2008
Chubut/102197/2008
Ghana/100/2008
Johannesburg/35/2008
Johannesburg/47/2008
Kursk/1/2008
Lyon/1059/2008
Seychelles/2010/2008
St. Petersburg/75/2008
St. Petersburg/85/2008

Jan-Mar 2008 (Hawaii-like and others)
Austria/405507/2008
Austria/405832/2008
Scotland/5/2008
Yokahama/35/2008

Northern EU-like
Norway/1687/07
Norway/1701/07
Norway/1731/07
Norway/1736/07
Norway/1743/07
Norway/1745/07
Norway/1747/07
Yokohama/77/08
Yokohama/78/08
Yokohama/79/08

Hawaii like and others
Aichi/76/08
Gifu-C/17/08
Gifu-C/38/08
Kobe/27/08
Shimane/59/08
Tochigi/8/08
Tochigi/28/08
Tochigi/34/08
Tottori/21/08
Tottori/23/08
Tottori/28/08
Tottori/29/08
Yamagata/68/08
Yokohama/22/08
Yokohama/30/08
Yokohama/31/08
Yokohama/34/08
Yokohama/35/08


Public Northern EU-like
Ankara-TR/170/2008
Arizona/03/2007
Arizona/13/2007
Arizona/14/2007
Arizona/15/2007
Bursa-TR/1231/2007
Cape Town/26/2008
England/557/2007
Hawaii/01/2008
Hawaii/02/2008
Hong Kong/17/2008
Illinois/10/2007
Indiana/01/2008
Istanbul-TR1198/2007
Istanbul-TR1219/2007
Istanbul-TR111/2008
Johannesburg/14/2008
Johannesburg/21/2008
Johannesburg/33/2008
Johannesburg/35/2008
Johannesburg/36/2008
Johannesburg/45/2008
Maryland/04/2007
Memphis/03/2008
Minnesota/01/2008
New Jersey/15/2007
New Jersey/16/2007
New Jersey/20/2007
New Jersey/05/2008
New Jersey/06/2008
New Jersey/10/2008
North Carolina/02/2008
Paris/341/2007
Paris/644/2007
Paris/749/2007
Paris/847/2007
Paris/910/2007
Paris/1154/2008
Paris/1157/2008
Paris/1170/2008
Paris/1208/2008
Pennsylvania/02/2008
South Carolina/01/2008
Washington/01/2008

Public Hawaii like and others
Florida/2/2008
Hawaii/21/2007
Hawaii/28/2007
Paris/963/2008

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