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H5N1 Clade 2.3.2 and 2.3.4 Mixtures Raise Concerns

Recombinomics Commentary 14:42
May 19, 2008

The release of sequences from whooper swans in Japan raises significant pandemic concerns.  Earlier reports from Japan and South Korea had indicated the sequences were the Fujian (clade 2.3) strain, which had caused fatal infections in China.  Recent fatalities in Vietnam are likely to also be from the Fujian strain.  In South Korea, a soldier tested positive for highly pathogenic H5, but the failure to detect N1 has led to media reports discounting the H5N1 infection in the soldier, and media reports have focused on HA sequences similar to clade 2.3.2.  However, the release of the whooper swan sequences show significant genetic mixing, including multiple clade 2.3.4 genes acquire via reassortment, and other polymorphisms, including those from North America and clade 2.2, acquired via recombination.

The new sequences show that the splitting of hairs between clade 2.3.4 and clade 2.3.2 is not likely to be relevant, because sequences from both sub-clades are present in the whooper swan isolates.  When H5N1 emerged from China in late 2003 / early 2004, the H5N1 was divided into multiple sub-clades.  Clade 1 was in human cases from Vietnam and Thailand in 2004.  In 2005, it was also in human isolates from Cambodia.  In 2005 human cases were also reported in Indonesia (clade 2.1) and China (clade 2.3).  The H5N1 in long range migratory birds at Qinghai Lake were clade 2.2, which subsequently spread to 50 countries west of China and caused human cases in 2006 in Turkey, Iraq, Azerbaijan, Egypt, and Djibouti.  In 2007 it caused human infections in Nigeria and Pakistan.

In China, all of the reported human cases fell into a further sub-division of the Fujian strain, clade 2.3.4.  Prior to the soldier in South Korea, all reported clade 2.3.2 cases had been in birds.  However, media reports now indicate that the South Korea sequences are related to human isolates from Vietnam.  Although 2007 sequences from ducks in Vietnam have been released, none of the human sequences, including 2008 isolates, have been released.  Similarly, the sequence of the clade 2.3.2 vaccine target has also been withheld.

Thus, the analysis of the released sequences from Japan is hampered by the withholding of related sequences from Hong Kong, Vietnam, and South Korea.  Similarly, there are few recent H5N1 sequences released from China.

WHO has called for more collaboration on H5N1 research.  Such collaborations can begin with the release of the above withheld sequences.  Japan has set the bar by promptly releasing sequences from the whooper swans on Hokkaido.  It is time for neighboring countries to follow suit.

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