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H5N1 Evolution in Indonesia

Recombinomics Commentary
June 7, 2007

"Virus samples from poultry cases have increasingly shown a similarity in their amino acid structure to virus samples extracted from humans," Wayan Teguh Wibawan told Reuters.

"This makes it easier for the virus to attach to human receptors," he said, referring to receptor cells lining the human throat and lungs.

For the H5N1 virus to pass easily from bird to human, it would have to be able to readily attach itself to these special cells.

For the moment, because H5N1 is a bird virus, it has evolved to easily attach to these receptors in poultry. Humans have a different type of receptor site, making it harder for people to become infected.

Wayan said he had spotted "gradual changes" in the virus sample he receives every month. He did not give details on these gradual changes.

The above comments may be related to changes seen in poultry H5N1 isolates from Indonesia. The first reports on H5N1 sequences in humans in Indonesia (Clade 2.1), showed that the sequences were significantly different than the sequences found in Indonesian poultry.  These match failures were discussed at a WHO sponsored meeting in Jakarta last summer.

Presentations at that meeting noted that human isolates largely had a novel HA cleavage site, RESRRKKR, as indicated in HA phylogenetic trees.  However, these differences were seen in all eight gene segments, strongly suggesting that human H5N1 infections in Indonesia were linked to an evolving reservoir that was not well represented by the public poultry isolates, although the chnages were in a cat from Indramayu.

Consequently, a batch of 91 poultry samples was sent to the WHO affiliated H5 reference lab in Australia.  Over 50 sequences from those samples were made public, but these samples largely lacked the novel cleavage site.  It was in one isolate from Indramayu, and two from central Sumatra.  These samples were from isolates collected in late 2005 and early 2006.

However, new sequences were released in February, 2007 from isolates collected in the middle of 2006.  In contrast to the earlier poultry sequences, these isolates were much more similar to the human H5N1 isolates.  Twelve had the novel cleavage site as well as additional HA changes that were largely limited to the human isolates.

Thus, the WHO data from February, had evidence that the poultry isolates in mid-2006 were more closely matching the human sequences.  As the sequences become more closely related, the chance of new acquisitions via recombination also increases, because of increased regions of identity.

The comments above suggest that these changes may be continuing, raising concerns that the poultry isolates were now efficient at infecting humans.

Since H5N1 is constantly evolving, the release of human and poultry Indonesian H5N1 sequences from 2007 would be useful.

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