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Novel HA Polymorphism in H5N1 from Turkish Child Fatality

Recombinomics Commentary

January 12, 2006

the change was found in one sample of H5N1 isolated from a Turkish child who recently died of the infection. The hemagglutinin protein, which the virus uses to attach to cells of the respiratory tract, had an alteration not usually seen in avian influenza viruses

The above comment indicates a novel polymorphisms was found in the Ha of H5N1 isolated form one of the two siblings that died at the Van hospital.  It is unclear if the change is limited to the one isolate, or the one isolate is the only one sequenced thus far.  Earlier reports indicated initial sequence data showed the H5N1 H and N sequences were distinct from the Turkey sequence from October, and were like the recent sequences from the Ukraine which were said to be "unique" and "dangerous to humans".

The number of cluster, the size of the clusters, and the clustering of clusters all suggested that the H5N1 in Dogubeyazit more efficient at infecting humans.  The change described above could provide a mechanism for the increased efficiency.

One change that was of concern was S227N, which had been previously found in only two H5N1 isolates.  That change increased the HA affinity for human receptors and decreased the affinity for avian receptors.  It had previously been isolated form Hong Kong patients who had developed bird flu symptoms while in Fujian Province.

The S227N polymorphisms could be acquire by the wild bird HA via homologous recombination with H9N2 indigenous to the Middle East.  The recent isolates from Israel had the appropriate donor sequence to generate S227N.  The above comments do not provide enough information to determine if the change is S227N or a similar change that increase the infectivity of human cells.

This change is cause for concern.  It would be useful to know if it was limited to patients in eastern Turkey or was present in isolates from patients throughout Turkey. 

In either event, the genetic change is cause for concern because it was closely related to H5N1 sequences transmitted and transported by migratory birds, and therefore may have already spread well beyond eastern Turkey. 


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