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H5N1 RBD Changes Increase Pandemic Concerns in China
Recombinomics Commentary
November 7, 2006

The recent H5N1 sequences from China include four sequences from geese in Shantou (A/goose/Shantou/2086/2006, A/goose/Shantou/239/2006, A/goose/Shantou/2104/2006, A/goose/Shantou/7775/2006) that have four non-synonomous changes in or near the receptor binding domain (V214M, K222R, V223I, and S227R).  Changes at position 227 (S227N) have been associated with increased affinity for human 2,6 receptors and decreased affinity for avian 2,3 receptors.  Although affinity changes for this particular combination of changes has not been reported, the presence of this number of changes in or near the receptor binding domain is cause for concern.

These changes appear to have been generated via recombination because two of the changes are circulating in northern China (K222R in A/goose/Jilin/hb/2203(H5N1)) or Japan (V223I in A/chicken/Yamaguchi/7/2004(H5N1)) and recombination between H5N1 in northern China nad Japan is not uncommon.

As the diversity in receptor binding domain sequences increase, the potential for additional changes via receombination also increases.  Thus, circulation of a large number of receptor binding domain sequences co-circulating in H5N1 creates a serious pandemic concern.

This concern is increased by the withholding of current sequences as well as a questionable surveillance system, since only one Qinghai sequences has been reported in eastern China.

The sequences from avian and human H5N1 isolates from China in 2005 and 2006 should be released immediately.  H5N1 sequences from 1997-2004 demonstrate frequent recombination in northern China, and a robust database is required to determine the likelihood of additional recombination.

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