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Confusion Over WHO Sequestered Indonesian H5N1 Sequences

Recombinomics Commentary

May 30, 2006

the WHO maps referenced above indicate that although outbreaks of animal disease have occurred widely throughout the archipelago, so far human cases has occurred predominantly in the central region and in
northern Sumatra. The northern Sumatra cluster is geographically
detached from the main body of human cases and conceivably might be
associated with an atypical virus. - Mod.CP

The above comments by ProMed on the geographically distinct location of the  north Sumatra cluster may signal a new H5N1 bird flu strain.  This analysis contradicts the WHO update, which indicate the sequence was very similar to the bird isolates in Indonesia.  The comments highlight the need for the release of the sequences of the human isolates, and additional sequences from both wild and domestic bird sources.  Moreover, the matching of the novel cleavage site in humans in the Jakarta / West Java area with a cat H5N1 sequence suggests more mammalian sources should be tested, including swine.

Descriptions of the human sequences suggest there are at least three different strains of H5N1 in Indonesia that are causing human disease.  Although all three versions are clearly most closely related to H5N1 sequences in birds in Indonesia, the three sets of isolates are readily distinguishable.

The majority of the human  cases are in the area in and around Jakarta in West Java.  The sequences (HA and NA) of one human isolate have been made public.  The human HA sequence is most closely related to a subset of the poultry isolates, but is readily distinguished by a novel glycosylation site and a novel cleavage site, RESRRKKR.  The novel cleavage site is found in all but one of the human isolates and it is also found in a cat isolate.  The cleavage site has not been reported in any public sequence other than the human sequence deposited in the Los Alamos flu database on August 1, 2005 and made available on March 25, 2006.

The one human sequence in the Jakarta area that is different is from the second confirmed case, and thought to be linked to fertilizer containing bird feces.  Thus, only one human isolate in the Jakarta / West Java area has been linked to a bird source, even though the cases have been reported since July of 2005, and the number of cases has recently spiked higher.

The Sumatra cluster appears to have the common H5N1 cleavage site of RERRRKKR, but it amantadine resistant, while the isolates from the Jakarta area are amantadine sensitive.  More information on the three distinct strains of H5N1 infecting humans in Indonesia requires analysis of the sequences sequestered in the WHO private database. 

These sequences should be released immediately.

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