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H5N1 Sequences from Patients in Turkey
Recombinomics Commentary
January 8, 2006
Perdue also said a preliminary comparison of viral samples taken from human cases and from affected poultry suggests the viruses that have infected these children remain closely related to the viruses circulating in chickens.
"All the genes haven't been sequenced. But it's good news that at least in the hemagglutinin and neuraminidase, the genes that have be en partially sequenced, that they're very closely related,"
The above comments on the initial sequencing data imply that there has been no reassortment in the H or N genes. The close homology between the human and bird versions also suggest that the infections in humans throughout Turkey are due to H5N1 transmition and transport by migratory birds.
The comments also suggest that the sequences are closely related to the prior sequences in the area, including earlier isolates from Turkey, which have the HA cleavage site of GERRRKKR. Isolates from the region (Romania, Ukraine, Volga Delta, Tula, Kergan, and earlier isolates from various locations in Russia, Kazakhstan, Mongolia, and Qinghai Lake also have the GERRRKKR cleavage site.
However, there is evidence that the closely related isolates are evolving. A cleavage site of RERRRKKR was reported for some isolates on the Crimea peninsula. These isolates were described as "unique" and dangerous to humans.
Recent data has indicated that changes in one or two nucleotides in the HA sequence can have major affects for receptor binding activities. One such change, S227N, increases affinity for human receptors, and decreases affinity for avian receptors. Such a change can be generated by recombining the H5N1 sequences in migratory birds with the endemic H9N2 sequences found in poultry in the Middle East.
Such a change would be expected to lead to changes being described for the H5N1 in Turkey, which can now efficiently infect humans. Earlier H5N1 were not associated with human infections, although reports of exposed humans with pneumonia have been reported for Kazakhstan, Novisbursk, and Romania. Although these cases were not confirmed to be H5N1 positive, as seen by the testing of patients in Turkey, false negatives are common. In addition, an Israeli had detectable H5 antibodies, although some tests were negative for that case.
In Turkey however, the efficiency of infecting humans is more efficient as indicated by the large number of cases, the size of the familial clusters, and the clustering of clusters. These dramatic changes suggest the H5N1 sequence has changed, but full sequences will be required, since such changes may be limited to single nucleotide changes, especially in the HA gene.
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