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Unique Human H5N1 Bird Flu Sequences in Indonesia
August 7, 2006
The human H5N1 Indonesian sequences sequestered at the WHO private database at Los Alamos were released to the public on Friday. Prior to this release, only two sequences, the HA and NA of A/Indonesia/5/05 were public. Thus was the first human isolate in Indonesia and was placed in the WHO data base by the CDC on August 1, 2005 and released on March 25, 2006. The release on Friday dramatically increased the number of public sequences to 504 (8 gene sequences from 63 human isolates).
Phylogenetic trees of HA sequences in the private database were discussed at the recent meeting in Jakarta. Most of the human sequences had the novel HA cleavage site RESRRRKKR. However, these sequences, primarily from the Jakarta / West Java area, also had several additional changes in HA and they formed a separate branch on the tree. Moreover, there were no avian sequences on this branch.
This lack of matching avian sequences raised concerns about the origin of the human H5N1. As indicated above, the first human sequence was isolated in July, 2005. The public avian sequences were from a wide geographical range in Indonesia, but most were collected prior to the first human case. None of these 2003-2005 isolates had the novel cleavage site. More recent collections were sent to Australia for analysis and those avian sequences were not included in the released data.
Analysis of the newly released data indicates that the human isolates with the novel cleavage site have a large number of unique polymorphism not found in any public Indonesian avian sequence, although the unique polymorphisms are clearly on an Indonesian genetic background. These unique polymorphisms are only all eight gene segments adding additional evidence suggesting the majority of the human cases are not linked to avian H5N1 in Indonesia.
The acquired polymorphisms are not random. As noted earlier for the first human sequences, they can frequently be found in other polymorphism on other H5N1 genetic backgrounds. This same type of acquisitions have been noted in Qinghai isolates found in the Middle East, Europe, and Africa. Although the isolates have a Qinghai genetic background, they are punctuated with a variety of shared polymorphisms whose distribution is far from random. These polymorphism are acquired via recombination.
These acquisitions also can be used to trace origins. The human sequences in Indonesia have a number of mammalian polymorphisms that are frequently found in isolates from humans, swine, dogs, and horses. In addition, a cat isolate, A/feline/Indonesia/CDC1/2006, matches the majority of the human isolates in all eight gene segments. A couple of the M polymorphisms are lusted below with isolates that share the polymorphism.
The presence of these polymorphism in mammalian isolates and the absence in Indonesian avian isolates, raises serious concerns about the origin of the H5N1 infections in Indonesia.
ISDN137455 A/Feline/Indonesia/CDC1/06 2006 H5N1
ISDN133318 A/Indonesia/283H/2006 2006 H5N1
ISDN133325 A/Indonesia/286H/2006 2006 H5N1
ISDN138749 A/Indonesia/292H/2006 2006 H5N1
ISDN136850 A/Indonesia/304H/2006 2006 H5N1
ISDN140927 A/Indonesia/542H/2006 2006 H5N1
ISDN137450 A/Indonesia/CDC326/06 2006 H5N1
ISDN137452 A/Indonesia/CDC326n/06 2006 H5N1
ISDN137451 A/Indonesia/CDC326t/06 2006 H5N1
ISDN137453 A/Indonesia/CDC329/2006 2006 H5N1
ISDN137454 A/Indonesia/CDC357/06 2006 H5N1
ISDN181368 A/Indonesia/CDC523/2006 2006 H5N1
ISDN183298 A/Indonesia/CDC523E/2006 2006 H5N1
ISDN183306 A/Indonesia/CDC523T/2006 2006 H5N1
ISDN183314 A/Indonesia/CDC582/2006 2006 H5N1
ISDN183702 A/Indonesia/CDC610/2006 2006 H5N1
ISDN183750 A/Indonesia/CDC634/2006 2006 H5N1
ISDN183758 A/Indonesia/CDC634P/2006 2006 H5N1
ISDN183766 A/Indonesia/CDC634T/2006 2006 H5N1
ISDN132407 A/Indonesia/239H/2005 2005 H5N1
ISDN132415 A/Indonesia/245H/2005 2005 H5N1
ISDN128028 A/Indonesia/6/2005 2005 H5N1
ISDN137460 A/Indonesia/CDC287e/05 2005 H5N1
ISDN137449 A/Indonesia/CDC292t/05 2005 H5N1
DQ124152 A/canine/Florida/43/2004 2004 H3N8
DQ124197 A/canine/Texas/1/2004 2004 H3N8
CY010565 A/swine/Spain/54008/2004 2004 H3N2
DQ124160 A/canine/Florida/242/2003 2003 H3N8
DQ124162 A/equine/Massachussetts/213/2003 2003 H3N8
DQ124188 A/equine/Ohio/1/2003 2003 H3N8
DQ222916 A/equine/Wisconsin/1/03 2003 H3N8
AY855344 A/equine/Kentucky/5/02 2002 H3N8
DQ376666 A/chicken/Taiwan/1205/01 2001 H6N1
CY004940 A/mallard/Alberta/30/2001 2001 H4N8
AF213916 A/Swine/Italy/25823/94 1994 H3N2
AJ311508 A/swine/Cotes d'Armor/3633/84 1984 H3N2
M55478 A/Swine/Germany/2/81 1981 H1N1
CY004984 A/mallard duck/Alberta/283/1977 1977 H8N4