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Uvs Lake H5N1 In Saudi Arabian Falcon

Recombinomics Commentary 19:48
May 12, 2008

The HA sequences from a falcon in Saudi Arabia, A/falcon/Saudi Atabia/6732-2/2007, is being released at Genbank.  The sequence is virtually identical to the earlier wild bird sequence from Saudi Arabia, A/houbara bustard/Saudi Arabia/6732-1/2007, and differs at one positive, A328G.  Thus, this sequence is also the Uvs Lake strain of clade 2.2.3. This close relationship suggest the NA sequence from the falcon will also have G743A, which was in the wild bird NA sequence as well as all Uvs Lake sequences isolated since early 2007.

The HA difference, A328G was present in the cat sequence from Germany in 2006.  In 2007, in addition to the above falcon sequence, A328G was also found in a subset of Egyptian human and bird sequences (see list here) which were from mild human cases in central and upper Egypt or bird sequences from the same areas.  Thus, like G743A, A328G is found on a number of distinct clade 2.2 isolates supporting acquisitions via recombination.  Moreover these acquisitions begin to define pathways which can be used to predict emerging sequences based on the movement of individual polymorphisms.  These pathways are best defined by a robust database, which is beginning to emerge, although many relevant sequences are still be hoarded.

Recently WHO members have suggested it was time for a new paradigm in influenza research, involving more sharing of samples and resources.  Of course such a new paradigm can begin with the WHO since they maintain a private database of H5N1 sequences and WHO regional centers are among the largest hoarders of sequence data.

The hoarding is across the board, but is quite glaring with respect to clade 2.2 sequences.  These sequences are found in long range migratory birds and have spread throughout Europe, the Middle East, and Africa following the massive wild bird outbreak at Qinghai Lake in May of 2005.  However, sequences from late 2005 and early 2006 from isolates in Europe and the Middle East still have not been released, creating giant holes in the sequence database.  Release of these sequences is long overdue, and WHO certainly has the ability of withholding support from its regional centers to force the release of the data.

As the data trickles out, it is becoming increasingly clear that H5N1 is evolving via recombination, and this evolution is quite predictable.  These observations are in conflict with the current influenza dogma which maintains that the changes described above are due to random errors and therefore cannot be predicted.  This thinking (which is shared among WHO consultants and regional centers) has lead to the catastrophic plan to hold pandemic vaccines until after a pandemic begins.  That plan is destined to fail because the stockpiled vaccine will be increasingly irrelevant due to H5N1 evolution away from the stockpiled vaccine, further evolution during the time for production of a new vaccine.  This approach will chase the target, as it evolves away from the new vaccine.

The predictability of H5N1 evolution allows for the identification of vaccine targets before the new viruses emerge, which will increase the efficacy of the vaccines.

Clearly the time for the release of the sequences is long overdue, as is the critical analysis of the outmoded tenet of influenza genetics which indicates H5N1 evolution is via random copy errors.

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