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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

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