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Human H5N1 From 2003 in Beijing

Recombinomics Commentary

June 22, 2006

The genomic sequence of the virus (A/Beijing/01/2003) was determined, and its eight segments were genetically related most closely to corresponding sequences of influenza A (H5N1) viruses that had been isolated from chickens in various regions of China in 2004. The segments of the polymerase basic protein 1 gene (PB) and the nonstructural gene (NS) were most closely related to those from Guangdong Province (in southeastern China), with 99 percent identity. The segments of the polymerase basic protein 2 gene (PB2) and HA gene were closest to those from Jilin Province (in northeastern China), with 99 percent and 97 percent identity, respectively. The segments of the neuraminidase gene (NA), nucleoprotein gene (NP), and M gene were closest to those from Hubei Province (in mideastern China), with 98 percent, 98 percent, and 99 percent identity, respectively, and the polymerase acidic protein gene (PA) segment was closest to that from Japan, with 99 percent identity.

These findings suggest that influenza A/Beijing/01/2003 may be a mixed virus.

The above comments from today's New England Journal of Medicine paper on a 2003 human case in Bejing provide additional information on the diversity of H5N1 that can cause fatal human infections.  The relationship to a variety of H5N1 bird flu isolates from poultry in China indicates the 2003 human isolate has undergone significant reassortment and recombination. The sequences summarized above are not yet available, but the HA and NA phylogenetic trees which include the isolate allow the new sequences to be positioned relative to other H5N1 sequences in the public domain.

The HA tree shows the 2003 human sequence, A/BJ01/2003, which is most closely related to 2001 and 2002 H5N1 isolates from China.  The current H5N1 isolates from humans are on a higher branch, which has Qinghai sequences (represented by Gs/QH/5/2005) at the bottom, Indonesian sequences (represented by Ck/Indonesia/2A/2003) in the middle, and Fujian sequences from China (represented by Dk/Fj/1734/2005) near the top of the branch. The top of the tree has human sequences from Vietnam and Thailand which represent clade 1.

These new data raise questions on the number of unreported human cases in China.  Earlier in 2003 a family from Hong Kong returned from a trip to Fujian province.  They were infected with H5N1, listed as A/HK/212/2003 and closer to the top of the tree.  Thus, it appears that at least two genetically diverse versions of H5N1 were in humans in China in 2003.

This year all reported sequences from China are the Fujian strain, but the number of unreported cases in the past and present, remain unclear.

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