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Recent Human and Avian H5N1 Sequences Do Not Match

Recombinomics Commentary

August 10, 2006

Concern was expressed at a recent meeting in Jakarta on the failure to identify matching H5N1 from humans and poultry in Indonesia.  The vast majority of the human cases have a novel HA cleavage site of RESRRRKKR.  This sequence is not found in any isolate represented at GenBank or Los Alamos.  Phylogenetic trees presented at the meeting indicated the differences extended beyond the cleavage site.  The human cases form a branch on the tree that contained no avian sequences.

On Friday, H5N1 sequences generated at the CDC in Atlanta and Hong Kong University in Hong Kong were made public.  The released sequences defined a large number of genetic differences in all eight gene segments which distinguished the human and avian sequences.

However, the human sequences had been collected in the past 12 months, while most of the avian sequences were collected at earlier dates.  The newly released sequences had two avian isolates from late 2005, but those two isolates also did not match.  Consequently additional samples were sent to Australia for sequencing to increase the sequence database of avian isolates, including more recent isolates.

The first sequences from those samples was released today at Los Alamos flu database. These samples were from 2005 and additional data is expected.  However, these initial samples do not match the human sequences.  None have the novel cleavage site.  On has the cleavage site most recently found in Vietnam, which is the common HPAI cleavages site, absent one R (RERRKKR).  The remaining isolates had the common cleavage site RERRRKKR.  Several were similar to the most recent avian sequences released by the CDC.

In addition, Hong Kong released recent collections from additional patients.  These patients had the novel cleavage site described above, indicating that the RESRRRKKR motif was quite stable and almost universally detected in the human samples.

The failure to match further increases the likelihood that the vast majority of the reported human H5N1 infections in the Jakarta area are not linked directly to poultry.

Below is a list of isolates that have one of the Qinghai HA polymorphism s.  The list includes the avian isolates most closely related to most of the human isolates from Java.
   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  
   DQ862002     A/duck/Egypt/2253-3/2006                           2006  H5N1  
   DQ464377     A/Egypt/2782-NAMRU3/2006                      2006  H5N1  
   ISDN136817  A/Feline/Indonesia/CDC1/2006                  2006  H5N1  
   ISDN133316  A/Indonesia/283H/2006                                2006  H5N1  
   ISDN133323  A/Indonesia/286H/2006                                2006  H5N1  
   ISDN138748  A/Indonesia/292H/2006                                2006  H5N1  
   ISDN136841  A/Indonesia/298H/2006                                2006  H5N1  
   ISDN136849  A/Indonesia/304H/2006                                2006  H5N1  
   ISDN138764  A/Indonesia/321H/2006                                2006  H5N1  
   ISDN138772  A/Indonesia/341H/2006                                2006  H5N1  
   ISDN140926  A/Indonesia/542H/2006                                2006  H5N1  
   ISDN187429  A/Indonesia/567H/2006                                2006  H5N1  
   ISDN187437  A/Indonesia/569H/2006                                2006  H5N1  
   ISDN187445  A/Indonesia/583H/2006                                2006  H5N1  
   ISDN187453  A/Indonesia/604H/2006                                2006  H5N1  
   ISDN136812  A/Indonesia/CDC326/2006                          2006  H5N1  
   ISDN136810  A/Indonesia/CDC326N/2006                       2006  H5N1  
   ISDN136811  A/Indonesia/CDC326N2/2006                    2006  H5N1  
   ISDN136814  A/Indonesia/CDC326T/2006                       2006  H5N1  
   ISDN136813  A/Indonesia/CDC326T/2006                       2006  H5N1  
   ISDN136815  A/Indonesia/CDC329/2006                         2006  H5N1  
   ISDN136816  A/Indonesia/CDC357/2006                         2006  H5N1  
   ISDN136908  A/Indonesia/CDC370/2006                         2006  H5N1  
   ISDN136909  A/Indonesia/CDC370E/2006                      2006  H5N1  
   ISDN137412  A/Indonesia/CDC370P/2006                      2006  H5N1  
   ISDN137413  A/Indonesia/CDC370T/2006                       2006  H5N1  
   ISDN137414  A/Indonesia/CDC390/2006                          2006  H5N1  
   ISDN181365  A/Indonesia/CDC523/2006                         2006  H5N1  
   ISDN183297  A/Indonesia/CDC523E/2006                       2006  H5N1  
   ISDN183305  A/Indonesia/CDC523T/2006                       2006  H5N1  
   ISDN183313  A/Indonesia/CDC582/2006                         2006  H5N1  
   ISDN183698  A/Indonesia/CDC610/2006                         2006  H5N1  
   ISDN183706  A/Indonesia/CDC623/2006                         2006  H5N1  
   ISDN183714  A/Indonesia/CDC623E/2006                      2006  H5N1  
   ISDN183722  A/Indonesia/CDC624/2006                         2006  H5N1  
   ISDN183730  A/Indonesia/CDC624E/2006                      2006  H5N1  
   ISDN183746  A/Indonesia/CDC634/2006                         2006  H5N1  
   ISDN183754  A/Indonesia/CDC634P/2006                      2006  H5N1  
   ISDN183762  A/Indonesia/CDC634T/2006                      2006  H5N1  
   DQ837590     A/turkey/Egypt/5613NAMRU3-T/2006        2006  H5N1  
   DQ497651     A/chicken/Gunung Kidal/BBVW/2005        2005  H5N1  
   ISDN129601  A/Chicken/Indonesia/CDC24/2005           2005  H5N1  
   ISDN129590  A/Chicken/Indonesia/CDC25/2005           2005  H5N1  
   ISDN187385  A/Chicken/Indonesia/Wates1/2005           2005  H5N1  
   ISDN187389  A/Chicken/Indonesia/Wates126/2005      2005  H5N1  
   ISDN187386  A/Chicken/Indonesia/Wates130/2005      2005  H5N1  
   ISDN187388  A/Chicken/Indonesia/Wates80/2005        2005  H5N1  
   DQ497652     A/chicken/Kulon Progo/BBVW/2005         2005  H5N1  
   DQ497643     A/chicken/Magetan/BBVW/2005               2005  H5N1  
   DQ320933     A/chicken/Wajo/BBVM/2005                     2005  H5N1  
   DQ497659     A/duck/Parepare/BBVM/2005                   2005  H5N1  
   ISDN130373  A/Indonesia/160H/2005                             2005  H5N1  
   ISDN130365  A/Indonesia/175H/2005                             2005  H5N1  
   ISDN130912  A/Indonesia/195H/2005                             2005  H5N1  
   ISDN132406  A/Indonesia/239H/2005                             2005  H5N1  
   ISDN132414  A/Indonesia/245H/2005                             2005  H5N1  
   ISDN125873  A/Indonesia/5/05                                        2005  H5N1  
   ISDN125783  A/Indonesia/5/2005                                    2005  H5N1  
   ISDN129527  A/Indonesia/7/2005                                    2005  H5N1  
   ISDN129921  A/Indonesia/CDC184/2005                       2005  H5N1  
   ISDN129922  A/Indonesia/CDC194P/2005                    2005  H5N1  
   ISDN136806  A/Indonesia/CDC287E/2005                    2005  H5N1  
   ISDN136807  A/Indonesia/CDC287T/2005                    2005  H5N1  
   ISDN136808  A/Indonesia/CDC292N/2005                    2005  H5N1  
   ISDN136809  A/Indonesia/CDC292T/2005                    2005  H5N1  
   ISDN129582  A/Indonesia/CDC7/2005                           2005  H5N1  
   M18450          A/Duck/Ireland/113/83                                1983  H5N8 

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