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Paradigm Shift Intervention Monitoring | Commentary Qinghai H5N1 Bird Flu Sequences in Indonesian Karo Cluster Recombinomics Commentary August 8, 2006 The recent human-to-human-to human transmission of H5N1 bird flu in the Karo Regency in Indonesia has caused concern. The cluster was the largest reported in Indonesia and represented yet another strain cable of causing human fatalities. Data presented at the meeting in Jakarta indicated the H5N1 in the cluster was distinct from the earlier human cases in Indonesia and also was distinct from other avian isolates. Initial analysis of changes between one of the cluster member and others in the clustered identified polymorphisms shared with Qinghai isolates. Acquisition of Qinghai polymorphism are cause for concern because the Qinghai strain carries PB2 E627K, which is linked to increased virulence in mice and allows the polymerase to function more efficiently at lower temperatures. Other polymorphisms associated with the Qinghai strain are also found in mammalian isolates, which was found in the M polymorphisms described previously. On Friday, the CDC and Hong Kong labs released the human H5N1 sequences sequestered in the WHO private database. Prior to the release, there were only two sequences from one isolate. The release increased the number of public sequences to more than 500. Analysis of the Karo cluster sequences indicated that there were a number of polymorphisms not found in other avian or human isolates from Indonesia. Analysis of these polymorphisms indicates many are shared by Qinghai isolates. Examples are listed below. These polymorphism are on an Indonesian genetic background. Thus, the isolates from the Karo cluster as well as the other human isolates are clearly from Indonesia. They share a number of polymorphisms fund only or predominantly in Indonesia. However, the punctuation of these sequences with Qinghai polymorphisms indicates these sequences are acquired via homologous recombination. These acquisitions run across the Karo genes indicting a dual infection can generate new polymorphism across multiple genes facilitating rapid evolution. The relationship of the polymorphisms to Qinghai isolates indicates these acquisitions are not random mutations, but are due to homologous recombination. Earlier, the Qinghai cleavage site was found in an avian isolate in Bali. In addition, the M gene of the father of the nephew in the cluster had another polymorphism found in both Qinghai isolates as well as human isolates. Below are the such polymorphism in HA The Qinghai isolates are in black bold. Karo cluster isolates are in red bold. Isolates from 2005 and 2006 with these shared polymorphisms are listed. HA polymorphisms First polymorphism DQ661910 A/chicken/Afghanistan/1207/2006 2006 H5N1 DQ862001 A/chicken/Egypt/2253-1/2006 2006 H5N1 DQ837587 A/chicken/Egypt/5610NAMRU3-F3/2006 2006 H5N1 DQ837588 A/chicken/Egypt/5611NAMRU3-AN/2006 2006 H5N1 DQ837589 A/chicken/Egypt/5612NAMRU3-S/2006 2006 H5N1 DQ447199 A/chicken/Egypt/960N3-004/2006 2006 H5N1 DQ673901 A/chicken/Ivory Coast/1787/2006 2006 H5N1 DQ676834 A/chicken/Krasnodar/01/2006 2006 H5N1 DQ676830 A/chicken/Mahachkala/05/2006 2006 H5N1 AM262541 A/chicken/Lagos.NIE/10.06/BA209/2006 2006 H5N1 AM262542 A/chicken/Lagos.NIE/10.06/BA210/2006 2006 H5N1 AM262543 A/chicken/Lagos.NIE/10.06/BA211/2006 2006 H5N1 AM262546 A/chicken/Lagos.NIE/8.06/SO300 2006/ 2006 H5N1 AM262547 A/chicken/Lagos.NIE/8.06/SO452/2006 2006 H5N1 AM262553 A/chicken/Lagos.NIE/8.06/SO493/2006 2006 H5N1 AM262572 A/chicken/Lagos.NIE/8.06/SO494/2006 2006 H5N1 DQ838517 A/chicken/Niger/2130-7/2006 2006 H5N1 DQ838516 A/chicken/Niger/2130-8/2006 2006 H5N1 DQ406728 A/chicken/Nigeria/641/2006 2006 H5N1 DQ862003 A/chicken/Sudan/1784/2006 2006 H5N1 DQ861999 A/chicken/Sudan/2115-12/2006 2006 H5N1 DQ862000 A/chicken/Sudan/2115-9/2006 2006 H5N1 DQ666146 A/Djibouti/5691NAMRU3/2006 2006 H5N1 DQ862002 A/duck/Egypt/2253-3/2006 2006 H5N1 DQ659113 A/duck/Niger/914/2006 2006 H5N1 DQ464377 A/Egypt/2782-NAMRU3/2006 2006 H5N1 DQ852600 A/grebe/Tyva/Tyv06-2/06 2006 H5N1 ISDN140810 A/Indonesia/534H/2006 2006 H5N1 ISDN140894 A/Indonesia/535H/2006 2006 H5N1 ISDN140895 A/Indonesia/536H/2006 2006 H5N1 ISDN140818 A/Indonesia/538H/2006 2006 H5N1 ISDN140896 A/Indonesia/546H/2006 2006 H5N1 ISDN185493 A/Indonesia/560H/2006 2006 H5N1 ISDN140835 A/Indonesia/CDC594/06 2006 H5N1 ISDN140843 A/Indonesia/CDC595/06 2006 H5N1 ISDN140851 A/Indonesia/CDC596/06 2006 H5N1 ISDN140859 A/Indonesia/CDC597/06 2006 H5N1 ISDN140866 A/Indonesia/CDC599/06 2006 H5N1 ISDN183782 A/Indonesia/CDC599N/2006 2006 H5N1 ISDN183738 A/Indonesia/CDC625/2006 2006 H5N1 ISDN183770 A/Indonesia/CDC625L/2006 2006 H5N1 DQ458992 A/mallard/Bavaria/1/2006 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 DQ837590 A/turkey/Egypt/5613NAMRU3-T/2006 2006 H5N1 AB263752 A/whooper swan/Mongolia/2/06 2006 H5N1 DQ643809 A/Zhejiang/16/2006 2006 H5N1 DQ659327 A/Bar headed goose/Qinghai/1A/2005 2005 H5N1 ISDN140934 A/Bar headed goose/Qinghai/1A/2005 2005 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 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 DQ650659 A/chicken/Crimea/04/2005 2005 H5N1 DQ650663 A/chicken/Crimea/08/2005 2005 H5N1 DQ676838 A/chicken/Dovolnoe/03/2005 2005 H5N1 DQ323672 A/chicken/Kurgan/3/2005 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 DQ449640 A/duck/Kurgan/08/2005 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 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 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 ISDN129523 A/turkey/Turkey/1/05 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 ISDN140936 A/Whooping swan/Mongolia/244/2005 2005 H5N1 DQ659326 A/Whooping swan/Mongolia/244/2005 2005 H5N1 second polymorphism AM262553 A/chicken/Lagos.NIE/8.06/SO493 2006 H5N1 DQ676830 A/chicken/Mahachkala/05/2006 2006 H5N1 ISDN138756 A/chicken/Malaysia/935/2006 2006 H5N1 SDN140810 A/Indonesia/534H/2006 2006 H5N1 ISDN140894 A/Indonesia/535H/2006 2006 H5N1 ISDN140895 A/Indonesia/536H/2006 2006 H5N1 ISDN140818 A/Indonesia/538H/2006 2006 H5N1 ISDN140896 A/Indonesia/546H/2006 2006 H5N1 ISDN185493 A/Indonesia/560H/2006 2006 H5N1 ISDN140835 A/Indonesia/CDC594/06 2006 H5N1 ISDN140843 A/Indonesia/CDC595/06 2006 H5N1 ISDN140851 A/Indonesia/CDC596/06 2006 H5N1 ISDN140859 A/Indonesia/CDC597/06 2006 H5N1 ISDN140866 A/Indonesia/CDC599/06 2006 H5N1 ISDN183782 A/Indonesia/CDC599N/2006 2006 H5N1 ISDN183738 A/Indonesia/CDC625/2006 2006 H5N1 ISDN183770 A/Indonesia/CDC625L/2006 2006 H5N1 ISDN133098 A/Turkey/12/2006 2006 H5N1 DQ643809 A/Zhejiang/16/2006 2006 H5N1 DQ371928 A/Anhui/1/2005 2005 H5N1 DQ371929 A/Anhui/2/2005 2005 H5N1 ISDN140934 A/Bar headed goose/Qinghai/1A/2005 2005 H5N1 DQ659327 A/Bar headed goose/Qinghai/1A/2005 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 DQ650659 A/chicken/Crimea/04/2005 2005 H5N1 DQ650663 A/chicken/Crimea/08/2005 2005 H5N1 DQ340848 A/chicken/Crimea/1/2005 2005 H5N1 DQ676838 A/chicken/Dovolnoe/03/2005 2005 H5N1 DQ320910 A/chicken/Hunan/999/2005 2005 H5N1 ISDN129601 A/Chicken/Indonesia/CDC24/2005 2005 H5N1 ISDN129590 A/Chicken/Indonesia/CDC25/2005 2005 H5N1 DQ095626 A/Chicken/Shantou/810/05 2005 H5N1 DQ279301 A/chicken/Tula/10/2005 2005 H5N1 DQ840519 A/chicken/Tula/Russia/Oct-5/2005 2005 H5N1 DQ095624 A/Chicken/Yunnan/447/05 2005 H5N1 DQ095625 A/Chicken/Yunnan/493/05 2005 H5N1 DQ320925 A/Chinese pond heron/Hong Kong/18/2005 2005 H5N1 DQ095629 A/Duck/Fujian/1734/05 2005 H5N1 DQ320900 A/duck/Guangxi/951/2005 2005 H5N1 DQ320901 A/duck/Guangzhou/20/2005 2005 H5N1 DQ095630 A/Duck/Hunan/114/05 2005 H5N1 DQ320911 A/duck/Hunan/1265/2005 2005 H5N1 DQ320902 A/duck/Hunan/127/2005 2005 H5N1 DQ320903 A/duck/Hunan/139/2005 2005 H5N1 DQ320904 A/duck/Hunan/149/2005 2005 H5N1 DQ320905 A/duck/Hunan/152/2005 2005 H5N1 DQ320906 A/duck/Hunan/157/2005 2005 H5N1 DQ320907 A/duck/Hunan/160/2005 2005 H5N1 DQ320912 A/duck/Hunan/1608/2005 2005 H5N1 DQ320913 A/duck/Hunan/1652/2005 2005 H5N1 DQ320908 A/duck/Hunan/166/2005 2005 H5N1 DQ320909 A/duck/Hunan/182/2005 2005 H5N1 DQ095631 A/Duck/Hunan/191/05 2005 H5N1 DQ230522 A/duck/Novosibirsk/56/2005 2005 H5N1 DQ497699 A/duck/Vietnam/S649/2005 2005 H5N1 DQ320922 A/Environment/Qinghai/31/2005 2005 H5N1 DQ320896 A/goose/Guangxi/345/2005 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 DQ371930 A/Guangxi/1/2005 2005 H5N1 DQ387854 A/mallard/Bavaria/1/2005 2005 H5N2 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 DQ095627 A/Quail/Shantou/911/05 2005 H5N1 DQ838509 A/teal/Italy/3812/2005 2005 H5N3 DQ851561 A/teal/Italy/3931/2005 2005 H5N2 DQ231240 A/turkey/Suzdalka/Nov-01/05 2005 H5N1 third polymorphism SDN140810 A/Indonesia/534H/2006 2006 H5N1 ISDN140894 A/Indonesia/535H/2006 2006 H5N1 ISDN140895 A/Indonesia/536H/2006 2006 H5N1 ISDN140818 A/Indonesia/538H/2006 2006 H5N1 ISDN140896 A/Indonesia/546H/2006 2006 H5N1 ISDN185493 A/Indonesia/560H/2006 2006 H5N1 ISDN140835 A/Indonesia/CDC594/06 2006 H5N1 ISDN140843 A/Indonesia/CDC595/06 2006 H5N1 ISDN140851 A/Indonesia/CDC596/06 2006 H5N1 ISDN140859 A/Indonesia/CDC597/06 2006 H5N1 ISDN140866 A/Indonesia/CDC599/06 2006 H5N1 ISDN183782 A/Indonesia/CDC599N/2006 2006 H5N1 ISDN183738 A/Indonesia/CDC625/2006 2006 H5N1 ISDN183770 A/Indonesia/CDC625L/2006 2006 H5N1 DQ497667 A/chicken/Dairi/BPPVI/2005 2005 H5N1 DQ497668 A/chicken/Deli Serdang/BPPVI/2005 2005 H5N1 DQ497665 A/chicken/Simalanggang/BPPVI/2005 2005 H5N1 DQ497669 A/chicken/Tarutung/BPPVI/2005 2005 H5N1 DQ497666 A/chicken/Tebing Tinggi/BPPVI/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 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 DQ449640 A/duck/Kurgan/08/2005 2005 H5N1 DQ497704 A/duck/Vietnam/376/2005 2005 H5N1 DQ676840 A/goose/Krasnoozerka/627/2005 2005 H5N1 ISDN128026 A/Indonesia/6/2005 2005 H5N1 DQ320897 A/quail/Guangxi/575/2005 2005 H5N1 DQ320137 A/swan/Astrakhan/1/2005 2005 H5N1 DQ840533 A/swan/Astrakhan/Russia/Nov-2/2005 2005 H5N1 ISDN117777 A/Viet Nam/JP4207/2005 2005 H5N1 Media Sources Phylogenetic Trees |
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