- Genetic sequencing of a particular fragment of the virus
relating to its virulence shows it is "analogous to the sequence of
the highly virulent [H5N1 sub-type] found in three species of migratory
water birds during the epidemic in May and June on Qinghai Lake in China,
writes Evgueny Nepoklonov, head of the main veterinary department at the
- The turkey virus was also subjected to a phylogenetic
analysis, which shows evolutionary history, of a crucial flu gene - the
neuraminidase gene. This provides additional evidence of link to the Chinese
migratory bird outbreak. "The preliminary data on the neuraminidase
structure show that it is practically identical to that of the isolate
from bar-headed geese (Anser indicus) from Qinghai Lake," says Nepoklonov.
- The above comments on sequences from H5N1 isolated in
the Chany Lake region of Novosibirsk leave little doubt that the H5N1 bird
flu was brought to the Chany Lake nature reserve via migratory birds (see
map). The sequences match in three key genes, the HA cleavage site, the
sequences of the NA gene, and a virulence fragment, which is almost certainly
the PB2 polymorphism, E627K striongly suggests that H5N1 migrated from
Qinghai Lake to Chany Lake.
- These data are cause for concern for many reasons. First
it is clear that the unique genetic sequences seen at Qinghai Lake did
not burn out when over 6000 water fowl died. The isolates from Qinghai
lake were particularly virulent, killing test chickens in 20 hours and
mice in 3-4 days. The virulence in mice correlated with E627K, which was
found in all 16 sequences deposited at GenBank. Prior to sequences from
Qinghai Lake, E627K had never been isolated in H5N1 from a bird. Previous
H5N1 isolates had been in variants that had grown in mouse brains. The
change was also found in tigers in Thailand and patients from Hong Kong,
Thailand, and Vietnam. The E627K was associated with a poor outcome. In
contrast, E627K is found in all human isolates that date back to the first
human isolate in 1933. The acquisition of mammalian sequences by H5N1
is associated with increased ability to cause human infections.
- The E627K is also associated with neurological problems.
H5N1 with that change have been isolated from the brains of mice. It
was also found in the Thailand tigers, which also had neurological problems.
The change is also in the 2004 H5N1 being used to test Tamiflu and create
a pandemic vaccine. That H5N1 causes hind leg paralysis in ferrets and
mice that died in the Tamiflu experiment had H5N1 in their brian.
- The similarity of the NA between Qingahi Lake and Novisibirsk
isolates suggest that the pandemic vaccine being developed worldwide will
have little effect on the H5N1 being transported by migratory birds. The
NA of the Qinghai Lake isolates differed from the 2004 isolate from Vietnam
by 13 amino acids. The HA from Qinghai lake has an even greater number
of amino acid differences, 18.
- Similarly, since Tamiflu targets NA, the near identity
between the Novosibirsk and Qinghai isolates and their close relationship
to NA from Vietnam suggest that more testing of Tamiflu will be required
to determine the optimal does for treating or preventing H5N1 infections.
- On a positive note, the similarities between the Novisbirsk
and Qinghai isolates suggests that the M2 in migratory bird isolates will
be sensitive to amantadine and rimantadine, although there are side effects
and resistance has developed in the past. However, the two anti-viral
agents are available in quantity in generic form, so the cost is markedly
less than Tamiflu.
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