- "It is interesting that the A/Hong
Kong/213/03 (H5N1) virus, which was isolated from a human and recognizes
both SA2,3Gal and SA2,6Gal (ref. 6), bound extensively to both bronchial
and alveolar cells."
-
- The above comments in tomorrow's Nature
may explain the large cluster in Turkey associated with S227N detected
in the index case. S227N had previously been shown to have reduced
affinity for avian receptors (SA2,3Gal) and increased affinity for human
receptors (SA2.6Gal). Although the recent paper in Science failed to find
increased affinity for SA2,6Gal, the S227N was on a genetic background
from an isolate in Vietnam which was distinct from the Hong Kong isolate
listed above. In Turkey, the S227N was on a Qinghai strain background,
which is different than both the Vietnam or Hong Kong strains used in the
lab experiments.
-
- However, the size of the cluster in
Turkey suggests that H5N1 was more efficiently transmitted human-to-human,
which would be consistent with increased affinity for SA2.6Gal receptors.
The H5N1 from the index case was said to be a mixture of S227N and wild
type S227. Only wild type was detected in the sister of the index
case, in contrast to the Hong Kong isolates which had S227N from both the
father and son. However, the Hong Kong isolates were grown on a canine
cell line, MDCK, as was the H5N1 used in the Nature paper. It is
unclear what was used to isolate H5N1 from the index case and his sister.
Isolation of H5N1 on chicken eggs can reduce or eliminate S227N.
-
- However, changes in the levels of S227N
and wild type could have been modulated in the patients. H5N1 was isolated
from lung tissue, which may have selected against S227N in vivo, since
the above data suggests the wild type would grow more efficiently in lung
tissue.
-
- Thus, the S227N could have facilitated
growth in the upper respiratory tract, while S227 could have been more
involved in growth in the lower respiratory tract. Genes encoding
S227 could have entered the upper respiratory tract in a pseudo-typed H5N1.
-
- These data could also explain the cluster
of cases in Azerbaijan which were fatal, yet efficient transmitted between
the index case, her two cousins, and a close friend.
-
- More sequence information on the Azerbaijan
cluster would be useful.
-
- © 2006 Recombinomics. All
rights reserved.
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