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Fujian H5N1 Sequences in China
Recombinomics Commentary
October 27, 2006

Hong Kong University has released H5N1 sequences from 404 isolates in China.  The isolates are from a number of provinces and locations in southern China, including Hong Kong, Shantou, and Fujian, Yunnan, Hunan, Guiyang, Guangxi province.  Most isolates are from ducks and geese, but many wild birds from Hong Kong (common magpie, crow, large-billed crow, white-backed munia, munia, Japanese white-eye, little egret, crested myna, and robin).

Although many of the 404 HA sequences (see list here) are partial sequences, the vast majority include the HA cleavage site, and the vast majority also have the novel Fujian cleavage site of PLRERRRK_R.  Some of the isolates have the more common cleavage site of PQRERRRKKR.

The Fujian HA cleavages site was first reported in 2005 in A/duck/Fujian/1734/05(H5N1).  As noted previously, all human sequences from China in 2005 and 2006 were the Fujian strain, as were the wild bird sequences in Hong Kong as well as sequences from Laos and Malaysia.  Thus, the current sequences confirm that the Fujian strain has become widespread in China.

The relase of 404 H5N1 sequences from isolates collected over a short time period (2005 and 2006) isa without precedent and provides insight into the evolution of H5N1 in China.  The analysis is supported by 156 PB2 sequences (see list here), which are largely full sequences and point to a wild bird origin of the sequences, modified by the acquisition of mammalian polymorphisms via recombination (see shared polymorphisms here).

Although the vast majority of the sequences are the Fujian strain, there is considerable heterogeneity, increasing pandemic concerns.  Analysis is somewhat hampered by a lack of full sequences in the database.  Initial analysis indicates the PB2 gene from
A/goose/Shantou/239/2006(H5N1) and other Shantou isolates is distinct from most of the other newly released PB2 sequences.  The 5’ end of the gene is related to A/duck/Yokohama/aq10/2003(H5N1), but is modified by the acquisition of human polymorphism.  The 3’ end of the gene is related to previously sequenced heron isolates (A/grey heron/Hong Kong/18/2005(H5N1) and A/grey heron/Hong Kong/837/2005(H5N1)) , but the earlier sequences only include the 3’ portion of the PB2 gene.

The current sequences significantly advance the understanding of H5N1 evolution in China, which enhances the full sequences from northern China, released earlier this month.  Those sequences also had clear-cut evidence of recombination, which was confirmed with full sequences of all eight gene segments.

Full sequences of all genes from the 404 H5N1 isolates from southern China would be useful, as would full sequences from earlier H5N1 isolates.  These data indicate H5N1 is evolving in a predictable manner via recombination.  A robust database of full sequences improves such analysis and increase the accuracy of predicting emerging sequences based on recombination between previously described parent sequences.

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