PB2 E627K in Indonesian H5N1 Bird Flu Patients
Recombinomics Commentary
August 4, 2006
The Indonesian government authorized the release of H5N1 sequences from Indonesia. Yesterday, the sequences generated by the CDC in Atlanta and Hong Kong University in Hong Kong were released to the public at the Los Alamos National Labs flu database.
As expected, most of the human isolates from patients on Java have a novel HA cleavage site, RESRRRKKR. However, these isolates also have a number of additional changes that readily distinguish the isolates from all public avian H5N1 sequences. Although the human sequences are clearly related to Indonesian avian sequences, they do not match, raising concerns over the source of the human infections. The only non-human sequence that does match is A/feline/Indonesia/CDC1/2006.
The sequences released included all eight gene segments. Analysis of the PB2 sequences indicates several patients who died in 2006 have the E627K polymorphisms. These patients were in West Java or in the Jakarta area and died between 2/10/06 and 4/26/06.
The presence of PB2 E627K in patients in Indonesia is cause for concern. The polymorphisms is found in all reported human isolates and increases polymerase activity at lower temperatures. The change is associated with increased virulence in mice. All Indonesian isolates listed below are from fatal cases.
DQ529292 A/chicken/Nigeria/641/2006 2006 H5N1
DQ533586 A/Cygnus olor/Italy/742/2006 2006 H5N1
DQ852607 A/grebe/Tyva/Tyv06-2/06 2006 H5N1
ISDN138771 A/Indonesia/321H/2006 2006 H5N1
ISDN183285 A/Indonesia/CDC370/2006 2006 H5N1
ISDN183288 A/Indonesia/CDC370E/2006 2006 H5N1
ISDN183289 A/Indonesia/CDC370P/2006 2006 H5N1
ISDN183293 A/Indonesia/CDC370T/2006 2006 H5N1
ISDN183296 A/Indonesia/CDC390/2006 2006 H5N1
ISDN183320 A/Indonesia/CDC582/2006 2006 H5N1
ISDN133103 A/Turkey/12/2006 2006 H5N1
ISDN133377 A/Turkey/15/06 2006 H5N1
ISDN133363 A/Turkey/651242/06 2006 H5N1
ISDN133371 A/Turkey/65596/06 2006 H5N1
AB264769 A/whooper swan/Mongolia/2/06 2006 H5N1
AB239300 A/bar-headed goose/Mongolia/1/05 2005 H5N1
DQ237956 A/bar-headed goose/Qinghai/0510/05 2005 H5N1
DQ095761 A/Bar-headed Goose/Qinghai/12/05 2005 H5N1
DQ095757 A/Bar-headed Goose/Qinghai/5/05 2005 H5N1
DQ095752 A/Bar-headed Goose/Qinghai/59/05 2005 H5N1
DQ095755 A/Bar-headed Goose/Qinghai/60/05 2005 H5N1
DQ095758 A/Bar-headed Goose/Qinghai/61/05 2005 H5N1
DQ095760 A/Bar-headed Goose/Qinghai/62/05 2005 H5N1
DQ095762 A/Bar-headed Goose/Qinghai/65/05 2005 H5N1
DQ095763 A/Bar-headed Goose/Qinghai/67/05 2005 H5N1
DQ095753 A/Bar-headed Goose/Qinghai/68/05 2005 H5N1
DQ095759 A/Bar-headed Goose/Qinghai/75/05 2005 H5N1
DQ100542 A/black-headed goose/Qinghai/1/2005 2005 H5N1
DQ100543 A/black-headed goose/Qinghai/2/2005 2005 H5N1
DQ100544 A/black-headed gull/Qinghai/1/2005 2005 H5N1
DQ095756 A/Brown-headed Gull/Qinghai/3/05 2005 H5N1
DQ650670 A/chicken/Crimea/08/2005 2005 H5N1
DQ449639 A/chicken/Kurgan/05/2005 2005 H5N1
DQ323675 A/chicken/Kurgan/3/2005 2005 H5N1
DQ389161 A/Cygnus olor/Astrakhan/Ast05-2-1/2005 2005 H5N1
DQ434890 A/Cygnus olor/Astrakhan/Ast05-2-10/2005 2005 H5N1
DQ343506 A/Cygnus olor/Astrakhan/Ast05-2-2/2005 2005 H5N1
DQ358750 A/Cygnus olor/Astrakhan/Ast05-2-3/2005 2005 H5N1
DQ365011 A/Cygnus olor/Astrakhan/Ast05-2-5/2005 2005 H5N1
DQ365001 A/Cygnus olor/Astrakhan/Ast05-2-6/2005 2005 H5N1
DQ363921 A/Cygnus olor/Astrakhan/Ast05-2-7/2005 2005 H5N1
DQ386305 A/Cygnus olor/Astrakhan/Ast05-2-8/2005 2005 H5N1
DQ399543 A/Cygnus olor/Astrakhan/Ast05-2-9/2005 2005 H5N1
DQ232608 A/duck/Novosibirsk/56/2005 2005 H5N1
DQ320856 A/Environment/Qinghai/31/2005 2005 H5N1
DQ100545 A/great black-headed gull/Qinghai/1/2005 2005 H5N1
DQ095754 A/Great Black-headed Gull/Qinghai/2/05 2005 H5N1
DQ232607 A/grebe/Novosibirsk/29/2005 2005 H5N1
DQ840532 A/swan/Astrakhan/Russia/Nov-2/2005 2005 H5N1
ISDN129518 A/turkey/Turkey/1/05 2005 H5N1
DQ138181 A /Viet Nam/DT-036/2005 2005 H5N1
DQ492899 A/Vietnam/CL105/2005 2005 H5N1
DQ492902 A/Vietnam/CL2009/2005 2005 H5N1
AB239307 A/whooper swan/Mongolia/3/05 2005 H5N1
AB239314 A/whooper swan/Mongolia/4/05 2005 H5N1
AB239321 A/whooper swan/Mongolia/6/05 2005 H5N1
DQ236079 A/cat/Thailand/KU-02/04 2004 H5N1
DQ530170 A/dog/Thailand-Suphanburi/KU-08/04 2004 H5N1
ISDN40383 A/Thailand/16/2004 2004 H5N1
AY907672 A/tiger/Chonburi/Thailand/CU-T3/04 2004 H5N1
AY907671 A/tiger/Chonburi/Thailand/CU-T7/04 2004 H5N1
DQ017251 A/tiger/Thailand/CU-T4/04 2004 H5N1
DQ017252 A/tiger/Thailand/CU-T5/04 2004 H5N1
DQ017253 A/tiger/Thailand/CU-T6/04 2004 H5N1
DQ017254 A/tiger/Thailand/CU-T8/04 2004 H5N1
AY651718 A/Viet Nam/1194/2004 2004 H5N1
ISDN40379 A/Viet Nam/1203/2004 2004 H5N1
AY651719 A/Viet Nam/1203/2004 2004 H5N1
AY818126 A/Viet Nam/1203/2004 2004 H5N1
AY651721 A/Viet Nam/3062/2004 2004 H5N1
DQ492894 A/Vietnam/CL01/2004 2004 H5N1
DQ492896 A/Vietnam/CL26/2004 2004 H5N1
DQ492897 A/Vietnam/CL36/2004 2004 H5N1
AY221588 A/Pheasant/Hong Kong/FY155/01-MB 2001 H5N1
AF508640 A/Ostrich/South Africa/9508103/95 1995 H9N2
Media Sources
Phylogenetic Trees