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S227N Re-emerges in Qinghai H5N1 in Egypt
February 9, 2007
NAMRU-3 has generated HA and NA sequences from H5N1 from the recent confirmed case in Fayyoum. These sequences are very similar to the HA and NA sequences from A/Egypt/0636-NAMRU3/2007 from the patient in nearby Beni Suef. Like the earlier HA sequence, there is a 3 BP deletion in the recent isolate.
However, the HA sequence was a mixture that included S227N, which is linked to increased affinity for human receptors.
S227N was first reported in both isolates from a family in Hong Kong who had gone to Fujian province for a visit in early 2003. The daughter died in China with bird flu symptoms and H5N1 was isolated from the father and son in Hong Kong. The father died, but both isolates (on MDCK cells from dog kidney) had S227N. A screening of H5N1 isolates in a receptor binding assay identified these two isolates as having increased affinity for 2,6 gal and decreased affinity for 2,3 gal.
Donor sequences for the acquisition of S227N in Qinghai H5N1 were present in H9N2 isolate that were almost exclusively in the Middle East. A warning was issued October 22, 2005 before Qinghai H5N1 had been confirmed in any human. S227N was then found in the index case for Turkey in early 2006. However, it was not in the isolate from his sister. Two additional sequences have been released, and S227N was in one of the two. Thus, S227N was in two of the four HA sequences from patients in Turkey, but in only one of the two siblings.
S227N was also in an human isolate from Egypt last year and S227N was found in an additional patient in Vietnam. However, the published data from a patient in Vietnam showed that S227N was in only one of three clones from that patient (all isolated with MDCK cells), indicating that patients with S227N had mixtures, and detecting S227N was most easily accomplished by looking at multiples clones from the same patient.
The latest sequence also is a mixture at the position encoding S227N. One sequence is wild type (with an A) while the other codes for S227N (with a G).
Although recent papers indicate H5N1 can be found in the upper respiratory tract, even when the binding preference is 2,3, sequences with a 2,6 preference lead to more sneezing (in ferrets described in Science), providing a mechanism for easier transmission. Thus, samples with S227N are more likely to lead to larger human clusters
S227N in Qinghai isolates from two patients in Turkey as well as two patients in Egypt indicates this receptor binding domain change is a major concern for the region.