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H5N1 S227R  In 2011 Whooper Swan In Hokkaido Japan
Recombinomics Commentary 13:10
February 3, 2011

The recent series of H5N1 in poultry and wild birds in Japan (see OIE reports here) has raised concerns.  Clade 2.3.2 (Fujian strain) had been circulating in wild birds in southern China for several years, but in 2008 it appeared in wild birds in Japan and poultry in South Korea.  It was the likely cause of a human cases in South Korea and subsequently appeared in wild birds and poultry in Primorsky.

The presence in wild birds led to the prediction that clade 2.3.2 would migrate to Mongolia and Russia, which was confirmed in 2009 isolates, which led to the prediction that clade 2.3.2 would migrate to Europe, the Middle East, and Africa, as predicted and confirmed for the Qinghai strain (clade 2.2).

A 2011 H5N1 sequence, A/whooper swan/Hokkaido/4/2011, has been released by Hokkaido University at Genbank. The sequence is clade 2.3.2, as expected, but it has the receptor binding domain change S227R.

In 2005, the acquisition of S227N by clade 2.2 was predicted, based recombination between donor sequences in H9N2 in the Middle East and Qinghai H5N1.  The ability of H5N1 with S227N to bind to human receptors led to the prediction of human cases in the Middle East, which was confirmed in the sequence from the index cases in Turkey in 2006. S227N was in two of the four human sequences in Turkey and appeared in subsequent human H5N1 sequences in Egypt. 

Moreover, additional receptor binding domain changes, V223I and M230I were found in human sequences from the Gharbya cluster

The presence of V223I and M230I in clade 2.3.2 Fujian sequences raised concerns about human transmission.

The detection of S227R in the recent H5N1 sequence from Japan increases those concerns.

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