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Turkish H5N1 Isolate Has Recominant HA S227N

Recombinomics Commentary

January 12, 2006

Virus from one of the patients shows mutations at the receptor-binding site. One of the mutations has been seen previously in viruses isolated from a small outbreak in Hong Kong in 2003 (two cases, one of which was fatal) and from the 2005 outbreak in Viet Nam. Research has indicated that the Hong Kong 2003 viruses bind preferentially to human cell receptors more so than to avian cell receptors. Researchers at the Mill Hill laboratory anticipate that the Turkish virus will also have this characteristic.

The above comments from the WHO update strongly indicate that the polymorphism found in the isolate from the fatal case in Turkey is S227N (also called S223N using H3 numbering).  The polymorphism lead to an increased affinity for human receptors and a deceased affinity for avian receptors.  Since the same change in receptor binding affinity  is expected from the Turkey isolate, the change would be S227N.

H5N1 has been evolving by capturing mammalian polymorphisms via recombination.  The HA wild bird sequence was used to identify donor sequences that would allow S227N to be created.  All of the donor sequences were in the HA of H9N2 isolates and all recent sequences were from the Middle East.  Since H5N1 had not been previously reported to have been in the Middle East, the wild bird H5N1 would have a unique opportunity to acquire this polymorphism which was not found in prior wild bird sequences tracing back to Qinghai Lake.  This acquisition would therefore be likely to happen when the H5N1 migrated into the region surrounding the Middle East where H9N2 was endemic.

This acquisition increased the efficiency for human receptors, resulting in the first reported human infections by H5N1 wild bird sequences migrating toward the west.  Such cases were reported in Turkey and the large number of cases and increased size of familial clusters indicated transmission to humans was more efficient than had been seen previously.  In additional, there have now been several reports of infection in young brothers tossing a dead bird or playing with gloves used to carry dead birds.  These are more examples of increased efficiency.  In the past, none of the H5N1 cullers in southeast Asia were reported positive for H5N1.  Now in addition to the young children, there are reports of soldiers developing symptoms after handling infected pigeons.

The latest results indicate H5N1 continues to acquire mammalian polymorphisms via recombination, not random mutation, and these acquisitions are leading to more efficient transmission of H5N1 to humans.


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