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Human H5N1 Iraq Sequence Includes N186S
March 15, 2006
HA sequences from Iraq have been released (A/human/Iraq/207-NAMRU3/2006(H5N1), A/domestic goose/Iraq/812/2006(H5N1), A/domestic cat/Iraq/820/2006(H5N1) by the US Naval Medical Research Unit in Cairo. As expected, all three have the HA cleavage site GERRRKKR, which is the signature sequence of the Qinghai strain of H5N1 bird flu. All three sequences are wild type at position 227 (serine).
The sequences are most closely related to the Kurgan isolate, A/chicken/Kurgan/3/2005(H5N1), which shares some polymorphisms with the Nigerian sequence, A/chicken/Nigeria/641/2006(H5N1). There are some polymorphisms that are specific to Iraq, including R565K.
The most intriguing change however is the change that is only in the human sequence, A609G, which creates N186S. This change could alter the affinity of receptor binding domain, which includes position 190, for human receptors. Donor sequences for this change were not identified in a search of the Los Alamos flu database, highlighting the need for a more complete database and release of the sequestered sequences.
The human sequence from Iraq is the first Qinghai related human sequence made public, and the cat sequence is the second mammalian Qinghai related sequence to be made public. Kudos goes to the Cairo research group for timely and transparent release of critical sequence information.
The above data provides more compelling reasons for the release of the H5N1 sequences sequestered by WHO, including human sequences from Turkey and Indonesia. The sequences each have unique features that are critical in mapping the paths of H5N1 spread as well as changes that will impact vaccine development. Release of the sequestered sequences is long overdue.