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Bird Flu Recombinants in Korea

Recombinomics Commentary
February 13, 2005

>> I consider Niman's scenarios unlikely and cannot vouch for the accuracy of the sequences, but silence on the part of the agencies seems like the wrong way to handle this. Full disclosure of whatever they know is indicated. <<

Effect Measure has posted a commentary of Recombinomics' Commentary entitled the "Recombinomics conundrum" and the above comment is on the WSN/33 situation in Korea.  There was also some commentary on recombination vs reassortment and the Korean situation addresses both of these issues.

New sequences from 2003 isolates in Korea have just come out at GenBank and are described in the current issue of Virology.  These sequences, like the 2004 swine sequences from Korea, have very clear examples of recombination.  The sequences from Korea are quite distinct from other sequences at GenBank, so verification of recombination is straightforward.  Many sequences are only partial sequences, so the extent of the recombination is unknown from the public information, but the existence of the recombination is quite clear.

The best example is in the PB2 gene of the swine isolates.  One sequence, S109, is almost all avian, but the first half of the sequence is missing.  However, the deposited sequences had 8 polymorphisms at the beginning of the deposited sequence, and all 8 exactly match WSN/33, indicating that there was recombination.  The missing portion has been sequenced, and it is all WSN/33, as is the corresponding region in S81, so both PB2 genes are recombinants, half human and half avian.

The controversy with the Korean sequences is really a technical issue.  WSN/33 is definitely a lab virus originally isolated in 1933 (the first human virus isolate, by Wilson Smith, and a variant was isolated from mouse brain in 1940, hence the name WSN, Wilson Smith, neurotropic).  The human portion of the swine sequences at GenBank are definitely WSN/33.  The real question is whether the sequences at Genbank came from swine on farms in Korea, or are a contaminant in the lab isolating the virus.  If they are the former, then somehow they moved from some lab somewhere and into the swine in 2004 (the avian portion matches 2004 Korean avian isolates).

The issue of WSN/33 sequences in swine in Korea was brought to the attention of the WHO in December, although the sequences were publicly available at the end of November. At least some at WHO knew of the data before the sequences were public (they were deposited October 24, 2004).  WHO also received a large number of media inquiries from major media organizations in December and January.  They gave out little information other than to say they were aware of the problem and were investigating. 

It has now been almost 4 months since the sequences were deposited and almost 3 months since they were made public.  The data has been independently verified by FAO in Korea and by now should have been verified outside of Korea.

The data at GenBank, as well as the discussion in the Virology paper, make it clear that there is considerable genetic instability in Korea.  An examination of the public data shows that the Korean isolates have clear cut recombination in PB2, NA, and NP genes.

The WHO has still not publicly commented. 

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