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Qinghai H5N1 M230I in German Eagle Owl

Recombinomics Commentary
April 6, 2007

H5N1 HA and NA sequences from 25 isolates from northern Germany were released at Genbank and Los Alamos (see list here).  One isolate was from a stone marten and the others were from dead wild birds.  The HA sequences fell into two groups.  One was closely related to previously released swan and cat sequences from northern Germany as well as a common buzzard from Denmark.  The second group was closely related to the northern Germany isolates under a Bavaria designation.  That series had one group from northern Germany that was similar to isolates from Switzerland, while the isolates from southern Germany formed a group with isolates from Italy and Slovenia.  Thus, although all isolates were the Qinghai (Clade 2.2) strain, the isolates had regional and sub-regional markers that clearly divided the isolates into sub-groups.

One isolate in the northern Germany/Bavaria group was an isolate from an eagle owl, A/eagle owl/Germany/R1166/06.  It had the northern Germany regional markers, G42A, G196A, G295A, C689T, C1012T, C1402T, C1480T.  However, the isolate also had G754A, which encodes M230IM230I was first reported in patients in Gharbiya in the Nile Delta.  It was found in the first Egyptian case, A/Egypt/12374-NAMRU3/2006, this season (September, 2006) as well as the Gharbiya cluster, A/Egypt/14724-NAMRU3/2006 and A/Egypt/14725-NAMRU3/2006 (December, 2006).  M230I is adjacent to the receptor binding domain and found in all three human season flu strains (H1N1, H3N2, influenza B).  All confirmed infections with M230I in Egypt were fatal.  The presence of M230I in an eagle owl in Germany in February, 2006 provides an M230I link via the Qinghai strain.  G754A was also in a chicken, A/chicken/Egypt/1080-NAMRU3/2006, from Damietta in the Nile Delta as well as a chicken from Gharbiya, A/chicken/Egypt/1892N3-HK49/2007 in February, 2007.

Another polymorphism in the eagle owl was A463G, which was found in human cases last season in Djbouti, A/Djibouti/5691NAMRU3/2006, as well as Damietta, A/Egypt/3458-NAMRU3/2006, providing another link between the eagle owl in northern Germany and the Nile Delta,

Earlier, another isolate from an eagle owl in northern Germany had been made public at Genbank and Los Alamos.  This isolate, A/eagle owl/Bavaria/10/2006, had the same set of northern Germany regional markers listed above, as well as G446A (see slide 43), which was found in three birds in Egypt this year.  All three isolates were from Gharbiya, A/chicken/Egypt/1890N3-HK45/2007, A/chicken/Egypt/1891N3-CLEVB/2007, A/duck/Egypt/1301-NAMRU3/2007.

Thus, although the three polymorphisms listed above were in northern Germany eagle owls on a northern Germany genetic background in the winter of 2006, the markers appeared in birds and patients in the Nile Delta in the spring of 2006 or the fall/winter of 2006/2007 in the Nile Delta on an Egyptian genetic background.  This type of movement of polymorphisms is most easily explained by recombination between H5N1 transported and transmitted by migratory birds and demonstrates the predictive power of these movements.

All of the H5N1 isolates west of China have been the Qinghai strain, yet these isolates have regional markers and additional sub-regional markers that move from one genetic background to another via recombination.  These movements can be well defined with a robust database and the predictions can be used to develop vaccine targets.

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