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Commentary

G743A Acquired by Vaccine Resistant H5N1 in Egypt
Recombinomics Commentary 09:11
May 27, 2008

New HA and NA sequences from Egypt have been released.  Two of the 2008 HA sequences, A/chicken/Egypt/1709-5/2008 and A/chicken/Egypt/1709-6/2008 are closely related to a sub-clade which was first reported in Egypt from isolates collected between mid-December, 2007 and mid-January, 2008.  This sub-clade was easily distinguished from earlier isolates, although it had the regional markers defined by earlier isolates from 2006 and 2007.  The majority of these isolates were from vaccinated flocks, indicating this sub-clade was vaccine resistant.  The clade also had a large number of non-synonymous changes.

The same sub-clade was found in Israel in early 2008, A/chicken/Israel/1055/2008.  Full sequences from this isolate were released and the NA sequence did not have G743A.  The NA sequences from the two Egyptian isolates described above were closely related to the NA sequence from Israel.  These three NA sequences differed from each other at two positions, One of the two positions (in A/chicken/Egypt/1709-6/2008) was G743A.

G743A had attracted interest in isolates collected form the beginning of 2007.  It had been appended onto multiple genetic backgrounds in Egypt.  In the same time frame, G743A was also appended onto easily distinguished sequences in Moscow and Ghana.  This concurrent acquisition was most easily explained by homologous recombination because like the vaccine resistant isolates describe above, the number of changes between those isolates with G743A and earlier precursors was minimal (2-6 changes), yet one of those small number of changes was G743A.  It was also found in clade 2.2.3 isolates from Kuwait, also collected in early 2007.  Sequences related to the Kuwait isolates were subsequently found throughout Europe from the summer of 2007 to early 2008.  All published NA sequences from these related isolates have G743A.  A similar acquisition was also seen in Nigerian isolates from early 2007.

Thus, the addition of G743A to the vaccine resistant sub-clade in Egypt and Israel is yet another example of a distinct clade 2.2 sub-clade with G743A appended.  This type of acquisition by recombination involving the appending of the same polymorphism onto multiple genetic backgrounds has important applications for vaccine development.

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