Novel H5N1 Cleavage Site in Duck Raises Pandemic Concerns
Recombinomics Commentary
August 31, 2006
The release of recent H5N1 bird sequences in Indonesia have identified a duck from that has the novel cleavage site, RESRRKKR. This sequence has been detected in almost all human H5N1 isolates in West Java, including the Jakarta area (see list below). The failure to find the sequence in domestic poultry has raised concerns regarding the origin of the human infections. Since most H5N1 testing in humans require a link to dead or dying poultry, a non-poultry origin, would indicate many infections from an alternate source would be missed.
Although the duck listed below is the first reported bird isolate with the novel cleavage site, the sequence contains an additional change in the cleavage site that is present in a small subset of the human cases. This change indicates the sequence in the duck is not the source of the majority of the human cases with the novel cleavage site, and suggests the duck H5N1 bird flu came FROM the human subset, which were isolated in 2005. The source of the majority of the human sequences has not been identified. The only non-human sequence to date is a cat sequence from Jakarta.
Since the new polymorphisms are acquired by recombination, the polymorphism provide a flight path that defines the origins of these polymorphisms. The silent change in the cleavage site traces back to wild birds, including low path H5 in Primorie and Chany Lake in southern Russia, as well as isolates from Mongolia. Last year the Qinghai strain of H5N1 was identified at Qinghai Lake in long range migratory birds. Those bird flu isolates in May were followed by identification of the Qinghai strain at Chany Lake in southern Russia and Erhel Lake in northern Mongolia. These reports compliment the earlier isolates of low path H5 in similar locations.
Wild birds were transmitting and transporting H5 sequences long before the Qinghai Lake reports, and continue to be a source of dual infections and recombination. This evolution is clearly represented in the newly acquired polymorphisms, and Qinghai sequences have been found in earlier isolates as well as the duck described above.
The finding of the novel cleavage site in a duck indicates these sequences are being transported by birds locally in Indonesia. The novel cleavage site has not been reported outside of Indonesia, and both bird and human isolates contain polymorphisms which are found in most or all Indonesian isolates.
The presence of these sequences in birds raises pandemic concern, but has yet to identify the reservoir for most of the human sequences from Java.
Sequences with change to create RESRRKKR cleavage site
ISDN207241 A/Duck/Indramayu/BBPW109/2006 2006 H5N1
ISDN136817 A/Feline/Indonesia/CDC1/2006 2006 H5N1
ISDN133316 A/Indonesia/283H/2006 2006 H5N1
ISDN133323 A/Indonesia/286H/2006 2006 H5N1
ISDN138748 A/Indonesia/292H/2006 2006 H5N1
ISDN136841 A/Indonesia/298H/2006 2006 H5N1
ISDN136849 A/Indonesia/304H/2006 2006 H5N1
ISDN138764 A/Indonesia/321H/2006 2006 H5N1
ISDN138772 A/Indonesia/341H/2006 2006 H5N1
ISDN140926 A/Indonesia/542H/2006 2006 H5N1
ISDN187429 A/Indonesia/567H/2006 2006 H5N1
ISDN187437 A/Indonesia/569H/2006 2006 H5N1
ISDN187445 A/Indonesia/583H/2006 2006 H5N1
ISDN187453 A/Indonesia/604H/2006 2006 H5N1
ISDN136812 A/Indonesia/CDC326/2006 2006 H5N1
ISDN136810 A/Indonesia/CDC326N/2006 2006 H5N1
ISDN136811 A/Indonesia/CDC326N2/2006 2006 H5N1
ISDN136813 A/Indonesia/CDC326T/2006 2006 H5N1
ISDN136814 A/Indonesia/CDC326T/2006 2006 H5N1
ISDN136815 A/Indonesia/CDC329/2006 2006 H5N1
ISDN136816 A/Indonesia/CDC357/2006 2006 H5N1
ISDN136908 A/Indonesia/CDC370/2006 2006 H5N1
ISDN136909 A/Indonesia/CDC370E/2006 2006 H5N1
ISDN137412 A/Indonesia/CDC370P/2006 2006 H5N1
ISDN137413 A/Indonesia/CDC370T/2006 2006 H5N1
ISDN137414 A/Indonesia/CDC390/2006 2006 H5N1
ISDN181365 A/Indonesia/CDC523/2006 2006 H5N1
ISDN183297 A/Indonesia/CDC523E/2006 2006 H5N1
ISDN183305 A/Indonesia/CDC523T/2006 2006 H5N1
ISDN183313 A/Indonesia/CDC582/2006 2006 H5N1
ISDN183698 A/Indonesia/CDC610/2006 2006 H5N1
ISDN183706 A/Indonesia/CDC623/2006 2006 H5N1
ISDN183714 A/Indonesia/CDC623E/2006 2006 H5N1
ISDN183722 A/Indonesia/CDC624/2006 2006 H5N1
ISDN183730 A/Indonesia/CDC624E/2006 2006 H5N1
ISDN183746 A/Indonesia/CDC634/2006 2006 H5N1
ISDN183754 A/Indonesia/CDC634P/2006 2006 H5N1
ISDN183762 A/Indonesia/CDC634T/2006 2006 H5N1
ISDN207111 A/Indonesia/CDC644/2006 2006 H5N1
ISDN207103 A/Indonesia/CDC644T/2006 2006 H5N1
ISDN204133 A/Indonesia/CDC669/2006 2006 H5N1
ISDN204141 A/Indonesia/CDC669P/2006 2006 H5N1
ISDN204149 A/Indonesia/CDC699/2006 2006 H5N1
ISDN130373 A/Indonesia/160H/2005 2005 H5N1
ISDN130365 A/Indonesia/175H/2005 2005 H5N1
ISDN132826 A/Indonesia/177H/2005 2005 H5N1
ISDN130912 A/Indonesia/195H/2005 2005 H5N1
ISDN132406 A/Indonesia/239H/2005 2005 H5N1
ISDN132414 A/Indonesia/245H/2005 2005 H5N1
ISDN125873 A/Indonesia/5/05 2005 H5N1
ISDN125783 A/Indonesia/5/2005 2005 H5N1
ISDN129527 A/Indonesia/7/2005 2005 H5N1
ISDN129921 A/Indonesia/CDC184/2005 2005 H5N1
ISDN129922 A/Indonesia/CDC194P/2005 2005 H5N1
ISDN136806 A/Indonesia/CDC287E/2005 2005 H5N1
ISDN136807 A/Indonesia/CDC287T/2005 2005 H5N1
ISDN136808 A/Indonesia/CDC292N/2005 2005 H5N1
ISDN136809 A/Indonesia/CDC292T/2005 2005 H5N1
ISDN129582 A/Indonesia/CDC7/2005 2005 H5N1
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