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Migrating H5N1 HA Cleavage Sites

Recombinomics Commentary

December 26, 2005

The latest OIE report from the Ukraine describes two HA cleavage sites detected in the Crimea peninsula.  Moreover, reports from the Volga Delta also described genetic sequences distinct from those found in migratory birds from Qinghai Lake.

However, the cleavage site from Qinghai Lake, GERRRKKR, is clearly expanding its global reach, which can be traced via sequences at Genbank and Los Alamos.  The above cleavage site was first detected in ducks in Hong Kong in 2000 (
A/Duck/Hong Kong/ww461/2000(H5N1), A/Duck/Hong Kong/ww487/2000(H5N1)).  It then reappeared in 2004 in chickens in Hubei Province (A/Chicken/Hu bei/14/2004(H5N1), A/chick/Macheng/2004(H5N1)) .  The two chicken sequences were closely related to each other and shared a number of polymorphisms with the isolates from Qinghai Lake.  Like the Qinghai Lake isolates, other polymorphisms were found in isolates from Japan and South Korea in the east and Sweden on the west.  These polymorphisms defined a northern migratory path shared by more recent wild bird flu isolate in Novosibirsk, Mongolia, and Kazakhstan.  In addition polymorphisms were shared with the first reported H5N1 isolate from Scotland in 1959 (A/chicken/Scotland/59(H5N1)), and South Africa in 1961 (A/tern/South Africa/61(H5N3)), indicating migratory birds have been transporting H5 sequences for some time. In addition polymorphism were found that were also in H5 isolates from the Americas, including the H5N2 isoaltes from the eastern seaboard of the United States. Shared polymorphisms were also found with H5N1 from tree sparrows in Henan.

These data predict that HPAI H5N1 will soon be extended worldwide.  This expansion is more easily monitored because the H5 sequences are in HPAI isolates which lead to fatal infections in domestic poultry, which are easily noted.

The GERRKKR cleavage site has expanded into Europe and has been reported in isolates from Turkey, Romania, Croatia, Ukraine, Volga Delta, and Tula.  Recently new HPAI H5N1 cleavage sites in Europe have been reported as well as in Mongolia and Hunan in Asia.  These novel cleavage sites highlight the rapid evolution of H5N1, as migration leads to dual infections and recombination, further destabilizing the H5N1 gene pool as H5N1 extends its global reach.


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