EARL NASH,
WTFG mutation Correspondent
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Although the number of Swine flu cases is declining, the fatal mutations of the H1N1 Swine flu strain--that were documented in the Ukraine outbreak--are increasing around the globe; the WHO says they are simply "due to independent random events," but virus mutation specialists disagree, they say that the increasing detection of these changes (strains D225G and D225N) "raises concerns that an increased frequency will lead to increased frequencies of severe and fatal cases.
The recent fatal cluster in Romania increases concerns that such clusters
will become more common."*
(The following article is from the scientifically technical recombinomics website http://www.recombinomics.com/whats_new.html * Henry L Niman, PhD )
Mill Hill has released a new
series of Ukraine sequences at GISAID. The 12 Dnipropetrovsk HA
sequences were from virus isolated from mammalian (MDCK) cells, while
the 6 Cherkasy HA sequences were from virus grown in eggs. The samples
did not have demographic data, but were isolated in early November,
when most fatal cases were in western Ukraine (see map).
The sequences were similar to the nasal wash sequences released earlier. Only one sample, A/Dnipropetrovsk/273?2009, had
D225G (as a mixture with wild type), and were the same sub-clade seen
in western Ukraine, bases on HA and NA markers. The HA marker that was
limited to Ternopil and Khmelmitski isolates in the earlier collections
was found on a subset of Dnipropetrovsk and Cherkasy isolates. The
marker on one Ternopil isolate that was shared with New York isolates
with D225N was also present in one of the Dnipropetrovsk sequences.
Thus, the new sequences indicated that same sub-clade was circulating
throughout Ukraine, while regional markers within the sub-clade were
present across a wide area in Ukraine. However, in fatal cases D225G,
D225N, or both markers were appended onto this background, and the
background had some region specific variation, consistent with
acquisition by homologous recombination.
It was the movement from background to background that was the foundation for the prediction
that fatal cases in Ukraine would have D225G/N. The newly released
sequences support that mechanism because the RBD changes appear on
multiple backgrounds at the same time as reported for changes in H5N1 as well as seasonal H1N1.
This same pattern seen previously is being repeated for pandemic H1N1
leading to H274Y appearing on multiple genetic backgrounds as well as
position 225 changes in HA also jumping from background to background.
Thus far the D225G and D225N acquisitions have been relatively rare.
Recently released sequences had the first example of D225G in India as well as D225N in Japan. Similarly, the additional examples in Ukraine and Moldova
which include both changes in the same samples significantly reduces
the likelihood that these changes are due to independent random events
which do not transmit, which is the current WHO working hypothesis.
Instead the appearance of the same change on multiple backgrounds at
the same time is more easily explained by recombination. The
increasing detection of these changes raise concerns that an increased
frequency will lead to increased frequencies of severe and fatal cases.
The recent fatal cluster in Romania increases concerns that such cluster will become more common.
