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Commentary
Focus On H5N1
Transmission Changes
Recombinomics Commentary 19:00
February 10, 2012
The above comments from a Helen Branswell piece on the upcoming WHO meeting on the censorship of H5N1 experiments confirms what is widely known about the papers being redacted and delayed at Nature and Science. Earlier Fouchier had mentioned that he was collaborating with Indonesia, and Kawaoka has published extensively on using samples and cells from Vietnam and Indonesia in receptor binding studies, as well as generation of reasortants between H5N1 and H1N1pdm09.
These prior publications highlight the folly of the NSABB request to hide the data, which is largely known and readily tweaked by imagined “terrorists” planning on generating a useless transmissible H5N1. Most who have given the use of H5N1 as a bioweapon some thought know that it can't be controlled and would be a poor choice, although the recent attention generated by the ill conceived NSABB may create unwarranted interest in a transmissible H5N1.
A serious program would use scientists who were familiar with the scientific literature, which is clearly lacking on the NSABB board. In 2006 Kawaoka published a paper in Nature that identified two receptor binding domain changes (N186K and Q196R) which enhanced binding and synergized with S227N. The paper was high profile and summarized by editors at Nature and widely discussed in media reports, including a summary by Reuters, which cited use of samples from patients in Vietnam and Indonesia.
However, the changes in the Nature paper were already signaled by H5N1 clusters due to clade 2.2 (Qinghai strain) in Turkey, Azerbaijan, and Iraq. On October 22, 2005 a warning was issued on S227N, which could be created via recombination between clade 2.2 donor sequences pairing up with H9N2 sequences in the Middle East. At the time, there had been no confirmed clade 2.2 human cases. The first confirmed cases were announced in early 2006, and S227N was confirmed in the index case in Turkey. That case was part of a large cluster and virtually all confirmed cases in Turkey were found in clusters. Only four human sequences were published, and S227N was in 2 of the 4 (and strongly suspected in the other two since of the two without S227N was from the sister of the index case. The clusters in Turkey were followed by clusters in Azerbaijan and sequences from cases had N186K. Similarly additional clusters were found in Iraq, and sequences from those clusters had N186S and Q196R. Moreover, since all outbreaks were due to clade 2.2, all also had PB2 E627K.
Thus, more than five years ago there were three receptor binding domain changes in H5N1 HA (N186K, S227N, and Q196R) as well as one change in PB2 (E627K), that would be likely candidates for the three changes Fouchier selected, which were enhanced by passage of the H5N1 through ferrets 10 times. Similarly. Kawaoka was well aware of these changes and are likely in the H5 from Vietnam that was placed on an H1N1pdm09 background to produce transmission in ferrets.
Thus, any serious H5N1 transmission program could easily replicate the detail being redacted or delayed at Nature and Science. Even if these four changes were not among the five changes identified in the Fouchier’s Science paper, a serious program would quickly identify a combination, since it is now known that efficient transmission has been achieved by two groups using very different approaches, which in fact could be used in combination (H5 changes could be placed on an H1N1pdm09 background and then passed in ferrets).
Thus, the withholding of the detail impacts scientists who are not actively doing transmission studies and diverts attention away from the fact that transmission is remarkably easy and natural sequences can recombine to create a combination that will efficiently transmit.
Thus, the real emphasis should be on fine tuning the redacted and delayed results, as well as vaccination efforts that will limit the spread of natural (or weaponized/manipulated) H5N1.
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