A193T Fixed in Tamiflu Resistant H1N1 in United States
Recombinomics Commentary 15:52
February 11, 2009

The US CDC has released 43 HA and 42 NA sequences from H1N1 isolates.  Two of the HA sequences were clade 2C (Hong Kong), which are oseltamivir sensitive and adamantine resistant.  One of the isolates was from the summer, while the other was from the fall.  The remaining 41 isolates were from the fall and the vast majority were collected in November and December, 2008.  The CDC is to be commended for the timely release of these important and evolving sequences.

These recent 41 isolates are all clade 2B (Brisbane) and all had H274Y.  Phylogenetic analysis indicated all isolates were related to a sub-clade that emerged last season in the United States and Europe.  All HA sequences from this sub-clade had A193T.  Over the summer the dominant sub-clade in South Africa was also from this sub-clade and had N187S and G189N in addition to A193T.  Recent sequences from Kenya also had this series as did an isolate from Washington State collected over the summer.

Isolates from the early fall in the US also evolved from this sub-clade.  All isolates had A193T and the dominant sequence also had G189V and H196R.  This dominant sequence was from isolates in HI, TX, and PA.  The same set of receptor binding domain changes, was report in Japan, including a large outbreak in elementary schools in Sendai.  These data supported the emergence of H274Y via recombination and hitch hiking, which was described in a recent paper in Nature Precedings.

The recently released sequences support and extend the above observations.  The majority of HA sequences have the same set of receptor binding domain changes, G189V, A193T, and H196R.  However, sequences with these changes were collected from isolates throughout the US (see list below).

A smaller series (see list below) was similar to the South Africa/Kenya sequences and had S187N and A193T.  However, these isolates had G189S instead of G189N, which was also noted in an earlier phylogenetic analysis, which included isolates from Seychelles.

Although there were some additional variations, all recent clade 2B isolates from the US had A193T and supported its role in the genetic hitch-hiking by H274Y, which has led to H1N1 levels approaching 100% across the northern hemisphere.  A recent WHO update on isolates collected over the same time period in the last quarter of 2008.  The only northern hemisphere country with levels lower than 97% was China.

G189V A193T H196R
A/Alaska/05/2008
A/Arizona/13/2008
A/Delaware/01/2008
A/Florida/18/2008
A/Florida/19/2008
A/Florida/21/2008
A/Hawaii/20/2008
A/Hawaii/21/2008
A/Hawaii/38/2008
A/Hawaii/46/2008
A/Idaho/23/2008
A/Illinois/15/2008
A/Illinois/16/2008
A/Illinois/17/2008
A/Massachusetts/08/2008
A/Michigan/05/2008
A/Michigan/06/2008
A/New Jersey/23/2008
A/Pennsylvania/08/2008
A/South Carolina/06/2008
A/Tennessee/11/2008
A/Texas/15/2008
A/Texas/16/2008
A/Texas/23/2008
A/Texas/27/2008
A/Texas/29/2008
A/Virginia/03/2008

S187N G189S A193T
A/Florida/24/2008
A/Minnesota/27/2008
A/Nebraska/07/2008
A/North Dakota/01/2008
A/Wisconsin/16/2008

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