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Hunan H5N1 Has Multiple Receptor Binding Domain Changes
Recombinomics Commentary
November 9, 2006

The recent publication in PNAS on the spread of the Fujian strain of H5N1 throughout southern China has focused attention on the 404 full or partial HA sequences released in association with the publication.  Researchers in northern China have indicated that the Fujian strain has been present since reports of H5N1 in Hunan in 2004.

These different points of view have focused attention on the H5N1 sequences and the data from the large number of HA sequences have highlight some of the changes in both the HA cleavage site as well as the receptor binding domain, two important regions of the HA gene involve in viral entry, which affects tissue tropism and lethality through the HA, as well transmission, which is affected by the receptor binding domain.

Some of the changes in these regions in isolates that did not have the Fujian s HA cleavage site of LRERRRKR, were striking in the receptor binding domain (RBD).  Five isolates from Shantou, had four changes in or near the RBD, V214M, K222R, V223I, S227R. Researchers at the Harbin facility released a recent isolate from Shanxi, which also had a large number of changes in the RBD, A188E, A189T, T192I, L194I, R220K, K222Q.

The isolate from Shanxi was closely related to two isolates from Hunan,
A/chicken/Hunan/2246/2006(H5N1) and A/chicken/Hunan/2292/2006(H5N1). which had two of the same changes, T192I and L194I as well as two additional changes, D187N and A189E.  The sharing of two of these changes highlights the widespread recombination throughout China, which is accelerating changes because the co-circulating sequences are becoming increasingly diverse.

This increased diversity requires a robust and current database of complete sequences fro all eight gen segments, which can be used to identify and confirm the origins of the changes as well as predict future changes, which can be used as vaccine targets.

This diversity has already led to four different strains of H5N1 causing fatal infections in humans, and vaccine targets have been selected from each group.  However, the dramatic changes in both the receptor binding domain, as well as the HA cleavage site highlights the need for current database of full sequences for all eight gene segments.

The withheld sequences should be released and the partial sequences should be completed as soon as possible.

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