H5N1 Clade 2.2 Recombinants in Qinghai Province in 2006
Recombinomics Commentary
July 3, 2007
H5N1 clade 2.2 sequences from wild birds in Qinghai province were made public at Genbank. The isolates were collected from a bar-headed goose (A/bar-headed goose/Qinghai/F/2006(H5N1)), and black-headed gull (A/black-headed gull/Qinghai/3/2006(H5N1)), and a swan (A/swan/Qinghai/01/2006(H5N1)), one year after the outbreak at Qinghai Lake in May, 2005. The isolates clearly demonstrate that clade 2.2 continues to be transported and transmitted by migratory birds. These isolates, like those reported in Europe, the Middle East, and Africa, have acquired new polymorphisms via recombination.
Sequences from all eight gene segments are over 99% identical to the consensus clade 2.2 sequence. However, the PB1 of the bar headed goose is only 94% identical, because it has acquired sequences similar to those found in H5N1 tree sparrows isolated in 2004 in Henan province. The clear-cut recombination is similar to the recombination noted previously in Henan isolates.
In addition to the PB1 recombination in the one isolate, all three have a novel HA cleavage site which is a recombined sequence with the 5’ portion encoding the amino side of the clade 2.2 cleavage site, GERRRKKR, while the 3’ portion encodes the carboxyl side of the clade 2.3 cleavage site, RERRRK_R, resulting in the recombinant GERRRK_R, which has a G at the first position, and a deletion of one of the tandem K's..
In addition to the acquisition of a large portion of PB1 from the tree sparrow sequences and a portion of the clade 2.3 HA cleavage site, the PB2, PB1, and MP genes have polymorphisms found in a cat and goose isolate from northern Germany, a buzzard isolate from Denmark, multiple swan isolates in Astrakhan, and multiple poultry isolates from western Africa (primarily Nigeria). An example of the polymorphism tracing for PB2 is here, PB1 is here, and MP is here.
These polymorphisms are appended onto 2-2 sequences that, like the HA cleavage site and portion of the PB1 gene, are found in H5N1 isolates in eastern China. This recombining of single nucleotide polymorphisms from distinct geographical regions illustrates how H5N1 evolves via recombination.
These acquisitions are similar to the concurrent acquisition of NA G743A by six different clade 2.2 genetic backbones in Moscow, Egypt, and Ghana. These acquisitions cast serious doubt on the basic tenets of influenza genetics, which are heavily dependent on random mutations and reassortment.
The tenets actively ignore homologous recombination, which is responsible for most of the genetic drift. This drift can be accurate monitored and predicted by polymorphism tracing like the examples noted above, which are useful for identifying vaccine targets.
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