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European Swine Signatures in H5N1 Bird Flu at Qinghai Lake

Recombinomics Commentary

July 20, 2005

The sequences from the Qinghai Lake H5N1 bird flu isolates have just been made public at GenBank.  There are 20 H5N1 isolates from 2005 which include 12 isolates from Qinghai Lake.  The 12 sequences for the M2 gene show wiid type sequences in the ion channel, indicating the H5N1 in the tested waterfowl are Amantadine sensitive.

These isolates have gained attention because the deaths of the water fowl by H5N1 is without precedent and Qinhai Lake is at the intersection of the two major migratory bird fly ways in Asia.  H5N1 at Qinghai Lake could be dispersed throughout Asia and into Europe and North America by migratory birds that use these two flyways.

In addition, all of the isolates have the PB2 polymorphism E627K.  This polymorphism is of concern because previously it was almost exclusively found in human flu such as H1N1, H3N2, and H1N2.  All published human sequences since 1933 have E627K.  This polymorphism was rarely found in sero-types associated with birds, like H5N1,  The only reported H5N1 isolates prior to the isolates at Qinghai that had the human polymorphism were two isolates from mouse brain, including one from the duck meat imported into Japan from Shandong, and human or wild cat isolates from the outbreaks in 1997 and 2004.

The H5N1 at Qinghai kills experimental chickens within 20 hours and experimental mice in 3-4 days.  There are also third party reports of human fatalities in Qinghai.  The concerns have been heightened because the birds will soon migrate away from Qinghai Lake and into Europe, eastern Asia, and the Indian subcontinent.

An initial analysis of the PB2 sequence reveals small clusters of polymorphisms not normally found in H5N1 sequences at Genbank.  One cluster matches the polymorphisms found in the PB2 gene of a 1999 isolate from a child in Hong Kong.  The isolate was unusual because it was closely related to European swine isolates, but there was no linkage between the Hong Kong child and Europe so the source of the H3N2 virus was unknown.  The PB2 genes from the water fowl at Qinghai Lake have additional polymorphisms found in H1N1 swine isolates from Europe.

The mammalian signatures, like the human signature, which is also found in many swine isolates, are indicators of an expanding host range.  Moreover, the European connection suggests that migratory birds do move sequences from Europe to Hong Kong via flyway intersections such as Qinghai Lake, where birds from Asia's eastern and north central flyway can give rise to dual infections, leading to novel recombinants.

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