Commentary
Norway
Tamiflu Resistant H1N1 Does Not Have A193T
Recombinomics Commentary
23:29
December 24, 2008
H1N1 HA sequences
from the 2007/2008 season in Norway have recently been released at
Genbank. Although the NA sequences have not been released,
several NA sequences were included in phylogenetic analysis of H1N1 in Japan,
and many additional HA sequences map with those know to come from H274Y
positive isolates. As indicated earlier, these sequences map to a
subset that has been called “Northern EU-like”, and this sub-clade
accounted for the vast majority of H274Y isolates in Europe and North
America, including the United States. In the 2007/2008 season,
over 65% of H1N1 isolates in Norway had H274Y. High levels were
seen in other European countries, including France, where the frequency
approached 50%.
However, during the 2008 flu season in the southern hemisphere, this
same sub-clade produced the 100%
Tamiflu resistance in South Africa. However, the subclade could
be subdivided more as it continued to evolve. The dominant
sub-clade of the sub-clade in South Africa had a cluster of changes
flanking the receptor binding domain position 190 (using H3 numbering),
which encoded for three non-synonymous changes, N187S, G189N,
A193T. Moreover, these polymorphisms could be found in circulating
H1N1 isolates. N187S was in clade IIC in Hong Kong, G189N was in
clade IIB in Kenya, and A193T was in more widespread clade IIC,
although the combination of polymorphisms were limited to isolates from
the 1940’s,
which also had A193T.
A193T was in 2007/2008 isolates from the United States, as well as one
isolate from England, which formed a sub-clade of the dominant
sub-clade. However, A193T was not in any of the isolates from
Norway, nor was it in isolates from France, or the South African
isolates that were not in the dominant sub-clade of the sub-clade.
Recently, the CDC released sequences from H1N1 isolates collected in
the United
States this season. All of these isolates mapped
to the earlier sub-clades with A193T. This sub-clade was even
more dominant than South African sub-clade because all isolates from
the United States not only had H274Y, but they also had A193T.
Although sequences from Europe have not been released, the same level
of dominance has been reported. All clade IIB isolates have been
Tamiflu resistant. The only sensitive H1N1 isolate in England was
clade IIC. For clade IIB all isolates in England, as well as Scotland,
Norway, and Austria have been resistant, as have all isolates in Canada.
Thus, the H1N1 sequences from the United States, where the only Tamiflu
sensitive isolate was clade IIC, are at 100% for clade IIB, and 98% of
H1N1 isolates are clade IIB (which is similar to Europe).
Therefore, it seems likely that clade IIB sequences in Europe and
Canada will have both H274Y and A193T.
Release of these
sequences would be useful.
Recombinomics
Presentations
Recombinomics
Publications
Recombinomics
Paper
at Nature Precedings