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Novel HA Cleavage Site in H5N1 Swan Isolates in Mongolia

Recombinomics Commentary

November 20, 2005

Four H5N1 wild bird flu isolates from Mongolia have been made available at GenBank.  These isolates are closely related to the wild bird flu sequences from Qinghai Lake in China and Chany Lake in Novosibirsk.  The whooper swan isolates came from a brain extract (A/whooper swan/Mongolia/3/05(H5N1)), cloacal swab (A/whooper swan/Mongolia/4/05(H5N1), or a tracheal swab (A/whooper swan/Mongolia/6/05(H5N1)).  It is unclear if the three whooper swan isolates are from different birds or different organs of the same bird.

The three sequences have polymorphisms that are unique for a given isolate, shared by 2 of the 3 swan isolates, or common to all three swan isolates but different than the other H5N1 isolates.  One polymorphism found only in the three swan isolates is A1059G in HA.  This changes the multi-basic cleavage site from RRRKKR to RRRRKR.  The former sequence is found in the first H5N1 isolate in Asia (Guangdong goose/96) and is present in most HPAI H5N1 in Asia.  There are few variations, such was the sequences from northern Vietnam that were missing one of the R's.  This deletion correlated with milder disease this year.

The RRRRKR motif is exclusively found in the three swan isolates.  It is not found in any other H5N1 isolate.  It is unclear if this change affects the pathogenicity of the H5N1.  OIE reports indicated all three isolates were HPAI, but the novel HA cleavage site could be a marker for new H5N1's migrating into China.

H5N1 was widely detected in Mongolia this summer (see map) and the initial outbreak in eastern China this season was in Inner Mongolia.  This was followed by outbreaks in Anhui and Hunan, suggesting the outbreaks were due to H5N1 migrating southeast out of Mongolia.  The first reported human cases in China were in Anhui and Hunan and may be linked to this new HA cleavage site.

In any event, the novel cleavage site offers of new marker for following HPAI H5N1 migrating out of Mongolia, and may mark novel pathogenicities in humans.


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