Qinghai H5N1 Bird Flu Sequences in Bali Indonesia
Recombinomics Commentary
June 17, 2006
Five avian HA sequences from Bali Indonesia (see below) have become available at GenBank. The partial sequences include the HA cleavage site and four of the five isolates have the common cleavage site for Asian H5N1, RERRRKKR. However, A/duck/Badung-Bali/05/2005 has the Qinghai HA cleavage site, GERRRKKR. This cleavage site is almost exclusively found in Qinghai isolates (see list below) and represents the third distinct cleavage site in H5N1 from Indonesia. Human isolates in Western Java have the novel cleavage site RESRRKKR, which has not been identifiued in any reported H5N1 isolate.
In addition, the Bali isolate above has another polymorphism shared with Qinghai isolates as well A/chicken/Denpasar/01/04. This isolate has a third polymorphism shared with other Qinghai isolates.
Although these Bali bird flu isolates have Qinhai polymorphisms, their genetic backbone is clearly Indonesian. All five Bali isolates are most closely related to other Indonesian isolates. Thus, these isolates have acquired Qinghai sequence via recombination, which punctuates an Indonesian sequence.
The acquisition of these sequences signal dual infection between Indonesian isolates and Qinghai isolates. All Qinghai isolates reported to date have PB2 E627K, which has also been identified in the second human isolate, A/Indonesia/6/2005, and is suspected in the Medan cluster. The sole surving member of thet 8 person cluster has developed neurological complications, which are also associated with E627K.
The Qinghai sequences, including the HA cleavage site highlight the complexity of H5N1 in Indonesia and again emphasizes the need for the release of the sequences sequestered at the WHO private database.
The acquisition of the Qinghai sequences, including the HA cleavage site, which has been acquired on an Indonesian genetic background, signal active evolution via recombination, which is cause for concern.
WHO affiliated researchers have ignored the role of recombination in H5N1 evolution, and the sequestered sequences should be made public for in depth analysis.
New isolates:
A/duck/Badung-Bali/05/2005
A/duck/Buleleng-Bali/04/2005
A/duck/Jembrana-Bali/03/2005
A/chicken/Denpasar/02/2005
A/chicken/Denpasar/01/2004
Matching sequences in HA cleavage site
DQ661910 A/chicken/Afghanistan/1207/2006 2006 H5N1
DQ447199 A/chicken/Egypt/960N3-004/2006 2006 H5N1
DQ676834 A/chicken/Krasnodar/01/2006 2006 H5N1
DQ676830 A/chicken/Mahachkala/05/2006 2006 H5N1
DQ406728 A/chicken/Nigeria/641/2006 2006 H5N1
AM231714 A/common pochard/France/06167/2006 2006 H5N1
DQ515984 A/Cygnus olor/Czech Republic/5170/2006 2006 H5N1
DQ435200 A/domestic cat/Iraq/820/2006 2006 H5N1
DQ435201 A/domestic goose/Iraq/812/2006 2006 H5N1
DQ659113 A/duck/Niger/914/2006 2006 H5N1
DQ464377 A/Egypt/2782-NAMRU3/2006 2006 H5N1
DQ435202 A/Iraq/207-NAMRU3/2006 2006 H5N1
DQ458992 A/mallard/Bavaria/1/2006 2006 H5N1
DQ449031 A/mallard/Italy/332/2006 2006 H5N1
DQ440535 A/swan/Iran/754/2006 2006 H5N1
DQ412997 A/swan/Italy/179/06 2006 H5N1
ISDN136919 A/swan/Italy/179/2006 2006 H5N1
AM236074 A/turkey/France/06222/2006 2006 H5N1
AB233319 A/bar-headed goose/Mongolia/1/05 2005 H5N1
DQ137873 A/bar-headed goose/Qinghai/0510/05 2005 H5N1
DQ095621 A/Bar-headed Goose/Qinghai/12/05 2005 H5N1
DQ095617 A/Bar-headed Goose/Qinghai/5/05 2005 H5N1
DQ095612 A/Bar-headed Goose/Qinghai/59/05 2005 H5N1
DQ095615 A/Bar-headed Goose/Qinghai/60/05 2005 H5N1
DQ095618 A/Bar-headed Goose/Qinghai/61/05 2005 H5N1
DQ095620 A/Bar-headed Goose/Qinghai/62/05 2005 H5N1
DQ095622 A/Bar-headed Goose/Qinghai/65/05 2005 H5N1
DQ095623 A/Bar-headed Goose/Qinghai/67/05 2005 H5N1
DQ095613 A/Bar-headed Goose/Qinghai/68/05 2005 H5N1
DQ095619 A/Bar-headed Goose/Qinghai/75/05 2005 H5N1
DQ100554 A/black-headed goose/Qinghai/1/2005 2005 H5N1
DQ100555 A/black-headed goose/Qinghai/2/2005 2005 H5N1
DQ100556 A/black-headed gull/Qinghai/1/2005 2005 H5N1
DQ095616 A/Brown-headed Gull/Qinghai/3/05 2005 H5N1
DQ340848 A/chicken/Crimea/1/2005 2005 H5N1
DQ676838 A/chicken/Dovolnoe/03/2005 2005 H5N1
DQ449632 A/chicken/Kurgan/05/2005 2005 H5N1
DQ323672 A/chicken/Kurgan/3/2005 2005 H5N1
DQ190859 A/chicken/Novosibirsk/64/05 2005 H5N1
DQ190860 A/chicken/Novosibirsk/65/05 2005 H5N1
DQ190861 A/chicken/Novosibirsk/66/05 2005 H5N1
DQ231242 A/chicken/Suzdalka/Nov-11/05 2005 H5N1
DQ231241 A/chicken/Suzdalka/Nov-12/05 2005 H5N1
DQ279301 A/chicken/Tula/10/2005 2005 H5N1
DQ389158 A/Cygnus olor/Astrakhan/Ast05-2-1/2005 2005 H5N1
DQ434889 A/Cygnus olor/Astrakhan/Ast05-2-10/2005 2005 H5N1
DQ343502 A/Cygnus olor/Astrakhan/Ast05-2-2/2005 2005 H5N1
DQ358746 A/Cygnus olor/Astrakhan/Ast05-2-3/2005 2005 H5N1
DQ363918 A/Cygnus olor/Astrakhan/Ast05-2-4/2005 2005 H5N1
DQ365004 A/Cygnus olor/Astrakhan/Ast05-2-5/2005 2005 H5N1
DQ364996 A/Cygnus olor/Astrakhan/Ast05-2-6/2005 2005 H5N1
DQ363923 A/Cygnus olor/Astrakhan/Ast05-2-7/2005 2005 H5N1
DQ399540 A/Cygnus olor/Astrakhan/Ast05-2-8/2005 2005 H5N1
DQ399547 A/Cygnus olor/Astrakhan/Ast05-2-9/2005 2005 H5N1
DQ644959 A/duck/Badung-Bali/05/2005 2005 H5N1
DQ449640 A/duck/Kurgan/08/2005 2005 H5N1
DQ190858 A/duck/Novosibirsk/56/2005 2005 H5N1
DQ230522 A/duck/Novosibirsk/56/2005 2005 H5N1
DQ320922 A/Environment/Qinghai/31/2005 2005 H5N1
DQ676840 A/goose/Krasnoozerka/627/2005 2005 H5N1
DQ212792 A/goose/Novosibirsk/4/2005 2005 H5N1
DQ100557 A/great black-headed gull/Qinghai/1/2005 2005 H5N1
DQ095614 A/Great Black-headed Gull/Qinghai/2/05 2005 H5N1
DQ230521 A/grebe/Novosibirsk/29/2005 2005 H5N1
DQ190857 A/grebe/Novosibirsk/29/2005 2005 H5N1
DQ320919 A/migratory duck/Jiangxi/2136/2005 2005 H5N1
DQ320920 A/migratory duck/Jiangxi/2295/2005 2005 H5N1
DQ320921 A/migratory duck/Jiangxi/2300/2005 2005 H5N1
DQ453141 A/mute swan/Croatia/1/2005 2005 H5N1
DQ320137 A/swan/Astrakhan/1/2005 2005 H5N1
DQ231240 A/turkey/Suzdalka/Nov-01/05 2005 H5N1
DQ407519 A/turkey/Turkey/1/2005 2005 H5N1
AB233320 A/whooper swan/Mongolia/3/05 2005 H5N1
AB233321 A/whooper swan/Mongolia/4/05 2005 H5N1
AB233322 A/whooper swan/Mongolia/6/05 2005 H5N1
ISDN48972 A/Chicken/Hu bei/14/2004 2004 H5N1
AY830774 A/chicken/Macheng/2004 2004 H5N1
One of the Qinghai polymorphims
DQ231242 A/chicken/Suzdalka/Nov-11/05 2005 H5N1
DQ231241 A/chicken/Suzdalka/Nov-12/05 2005 H5N1
DQ644959 A/duck/Badung-Bali/05/2005 2005 H5N1
DQ231240 A/turkey/Suzdalka/Nov-01/05 2005 H5N1
DQ407519 A/turkey/Turkey/1/2005 2005 H5N1
AB212649 A/blow fly/Kyoto/93/2004 2004 H5N1
DQ644955 A/chicken/Denpasar/01/2004 2004 H5N1
AY609312 A/chicken/Guangdong/174/04 2004 H5N1
DQ320893 A/chicken/Guangxi/2439/2004 2004 H5N1
AB188824 A/chicken/Kyoto/3/2004 2004 H5N1
AB188816 A/chicken/Oita/8/2004 2004 H5N1
ISDN49016 A/Chicken/Yamaguchi/7/2004 2004 H5N1
AB166862 A/chicken/Yamaguchi/7/2004 2004 H5N1
AB189053 A/crow/Kyoto/53/2004 2004 H5N1
AB189061 A/crow/Osaka/102/2004 2004 H5N1
DQ320883 A/duck/Guangxi/1311/2004 2004 H5N1
DQ320885 A/duck/Guangxi/1586/2004 2004 H5N1
DQ320886 A/duck/Guangxi/1681/2004 2004 H5N1
DQ320890 A/duck/Guangxi/2291/2004 2004 H5N1
DQ320892 A/duck/Guangxi/2396/2004 2004 H5N1
DQ320879 A/duck/Guangxi/668/2004 2004 H5N1
AY639405 A/goose/China/F3/2004 2004 H5N1
DQ320881 A/goose/Guangxi/1097/2004 2004 H5N1
DQ320882 A/goose/Guangxi/1198/2004 2004 H5N1
DQ320888 A/goose/Guangxi/1832/2004 2004 H5N1
DQ320889 A/goose/Guangxi/2112/2004 2004 H5N1
DQ320891 A/goose/Guangxi/2383/2004 2004 H5N1
AY676035 A/chicken/Korea/ES/03 2003 H5N1
ISDN40921 A/Chicken/Korea/es/2003 2003 H5N1
AY651368 A/Ck/ST/4231/2003 2003 H5N1
AY676036 A/duck/Korea/ESD1/03 2003 H5N1
Third polymorphism
DQ231242 A/chicken/Suzdalka/Nov-11/05 2005 H5N1
DQ231241 A/chicken/Suzdalka/Nov-12/05 2005 H5N1
DQ231240 A/turkey/Suzdalka/Nov-01/05 2005 H5N1
AB212649 A/blow fly/Kyoto/93/2004 2004 H5N1
DQ644955 A/chicken/Denpasar/01/2004 2004 H5N1
AY609312 A/chicken/Guangdong/174/04 2004 H5N1
DQ320893 A/chicken/Guangxi/2439/2004 2004 H5N1
AB188824 A/chicken/Kyoto/3/2004 2004 H5N1
AB188816 A/chicken/Oita/8/2004 2004 H5N1
ISDN49016 A/Chicken/Yamaguchi/7/2004 2004 H5N1
AB166862 A/chicken/Yamaguchi/7/2004 2004 H5N1
AB189053 A/crow/Kyoto/53/2004 2004 H5N1
AB189061 A/crow/Osaka/102/2004 2004 H5N1
DQ320883 A/duck/Guangxi/1311/2004 2004 H5N1
DQ320885 A/duck/Guangxi/1586/2004 2004 H5N1
DQ320886 A/duck/Guangxi/1681/2004 2004 H5N1
DQ320890 A/duck/Guangxi/2291/2004 2004 H5N1
DQ320892 A/duck/Guangxi/2396/2004 2004 H5N1
DQ320879 A/duck/Guangxi/668/2004 2004 H5N1
AY639405 A/goose/China/F3/2004 2004 H5N1
DQ320881 A/goose/Guangxi/1097/2004 2004 H5N1
DQ320882 A/goose/Guangxi/1198/2004 2004 H5N1
DQ320888 A/goose/Guangxi/1832/2004 2004 H5N1
DQ320889 A/goose/Guangxi/2112/2004 2004 H5N1
DQ320891 A/goose/Guangxi/2383/2004 2004 H5N1
AY676035 A/chicken/Korea/ES/03 2003 H5N1
ISDN40921 A/Chicken/Korea/es/2003 2003 H5N1
AY651368 A/Ck/ST/4231/2003 2003 H5N1
AY676036 A/duck/Korea/ESD1/03 2003 H5N1
Phylogenetic Tree