Qinghai H5N1 Reservoir Linked to Germany
Recombinomics Commentary
May 4, 2007
The confirmation of H5N1 in Ghana for the first time, highlights the continued expansion of the geographical reach of the Qinghai (Clade 2.2) strain of H5N1. This strain was initially reported at Qinghai Lake in central China in May, 2005 and has since spread to almost 50 countries. Like Ghana, all countries west of China have reported the “Asian” strain of H5N1 for the first time, and all reported isolates have been the Qinghai strain.
Sequence analysis has demonstrated a steady accumulation of polymorphisms. The vast majority of these new acquisitions are readily detected in the sequence database, and most commonly found in earlier H5N1 isolates.
Egypt has had a recurrence of H5N1 infections this season in backyard poultry as well as human cases. Sequences of the isolates, released by US NAMRU-3 have provided a detail record of H5N1 evolution. The genetic complexity of H5N1 this season is more complex and most of the newly acquired polymorphisms can be found in H5N1 isolates from eastern Asia. As the data base of Qinghai sequences increase, the detection of the newly acquired sequences in earlier Qinghai isolates becomes easier.
One polymorphism, HA M230I was found in human cases in Egypt this season. This polymorphism is adjacent to the receptor binding domain, and found in all three strains of season flu (H1N1, H3N2, influenza B). Moreover, all human isolates with M230I have been from fatal cases. M230I in Qinghai isolates was reported for the first time in these patients. However, recently released H5N1 sequences from 2006 isolates in Germany had M230I. It was in an eagle owl that was fatally infected with H5N1 in February, 2006 when many countries in Europe, the Middle East, and Africa reported H5N1 infections for the first time.
Recent isolates from Egypt had acquired another polymorphism, first reported in Qinghai isolate in Germany. This group included the eagle owl isolate. Remarkably, the polymorphism, NA G743A, was reported in six isolates in Egypt that were on four separate branches of an HA or NA phylogenetic tree. Earlier isolates from these branches to not have G743A, suggesting the acquisition was recent. At the same time, the polymorphism appeared in isolates from Moscow, which were closely related to Azerbaijan isolates from 2006, which also did not have G743A.
The simultaneous acquisition of NA G743A by eight isolates on five distinct branches of phylogenetic trees strongly suggests these polymorphisms were acquired by recombination involving similar parental strains.
At the same time as the above acquisitions, Nigeria reported its first H5N1 isolate from a patient. The HA sequence from this patient had a number of polymorphisms that were shared with isolates from Egypt. However, the Nigerian isolate also had a polymorphism, G295A, that was found in German isolates (see list here), and the isolates matched those which had NA G743A. Thus, several polymorphisms that appeared in 2007 isolates in Russia, Egypt, and Nigeria trace back to the same set of 2006 isolates from Germany.
This polymorphism tracing provides additional evidence for evolution via recombination and identifies a common source for acquisitions found in 2007 isolates. More precise tracing of these polymorphisms will be enhanced by a more complete sequence database.
The current database still has major gaps due to the hoarding of Qinghai sequences from last season's outbreaks in Europe and the Middle East.
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