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Failure to Find H5N1 RBD Changes in Pakistan Cluster

Recombinomics Commentary 00:28
January 4, 2008

The genetic structure of H5N1 virus recovered from Pakistan's first confirmed human case of the illness suggests the virus did not mutate to become better adapted to humans, an expert with the World Health Organization said Thursday.

Dr. Frederick Hayden said initial sequencing of several genes of the virus showed no worrisome genetic changes. The London-based influenza laboratory that did the work reported that the virus was identical to a number of H5N1 viruses isolated from chickens in the region, he said.

"There were no adaptive mutations in the hemagglutinin that would suggest that it have moved towards human binding characteristics, which is of course good news,'' said Hayden, a medical officer with the WHO's global influenza program.

The comments above describe the failure to identify receptor binding domain changes associated with the large cluster in Pakistan.  Unfortunately, the samples had degraded and one of ten infected patients yielded a confirmatory test.  The comments above suggest that H5N1 was isolated, but detecting receptor binding domain changes is dependent on the isolation conditions, as well as as the sample itself.

The data from the one patient are analogous to the sequence from the sister of the index case in Turkey.  In that cluster the index case had the predicted receptor binding domain change, S227N.  However, the isolate from his sister did not.  Similarly, two additional sequences from the Turkey outbreak were released and one had S227N and the other did not.

There have also been examples in Vietnam and Thailand where one clone had one or more receptor binding domain changes while another clone from the same patient did not.

The sequence from the only confirmed case in Pakistan appears to match poultry sequences from the region.  This result is unfortunate. 

Virtually all Qinghai isolates from large clusters have receptor binding domain changes.  The failure to find such changes extends the technical fiasco associated with one of the largest clusters reported to date.

The technical failures remain a cause of concern, as does WHO’s interpretation that this failure is "of course good news."

Details of the isolation procedures and the release of sequences of clones would be useful.

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