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Fixed in Tamiflu Resistant H1N1
in United States
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
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
S187N G189S A193T
at Nature Precedings