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Astrakhan Mute Swan H5N1 Acquisition of Human Sequences

Recombinomics Commentary

February 26, 2006

As the Qinghai strain of H5N1 spreads in Europe, the Middle East, and Africa, sequences from isolates are appearing at Genbank.  Russia, Italy, and France are placing sequences at public databases shortly after Isolation.  2006 isolates from Nigeria, France, and Italy have already been deposited.  These are partial sequences of one or two genes.  Russia has also been quickly putting sequences on deposit.  The latest series are from 6 mute swan isolates in Astrakhan.  Although the deposits are closely related to the Qinghai isolates, they also have polymorphisms appended onto the Qinghai genetic background.  These acquired polymorphisms are not random mutations.  They are polymorphisms that are acquired via recombination.  The acquisition of clustered polymorphisms provides strong evidence that the polymorphism are not due to recent mutations.

One of the first cluster noted were the PB2 polymorphisms on all 16 isolates from Qinghai Lake.  These three polymorphisms were also on H1, H2, and H3 isolates from European swine, as well as a child in China who had been infected with a swine H3N2.  There have since been a number of PB2 sequences published and all Qinghai related sequences have E627K.  However, only the 16 isolates from Qinghai Lake have the 3 clustered polymorphism shared with European swine.

Another cluster of polymorphisms were also on PB2 but were unique to the isolates from Astrakhan.  The two polymorphisms were 23 BP apart and 5 of the 6 isolates have both and the other had one.  These two polymorphisms were found in a broad spectrum of bird serotypes. But all isolates were from North America suggesting the Qinghai strain of H5N1 has already migrated to North America.

There are 8 PB1 polymorphisms in these isolates that are not found on other Qinghai strains.  the polymorhisms are in at least 5 of the 6 Astrakhan isolates.  One of these polymorphisms is similar to the two on PB2.  All recent isolates with this polymorphism are from North America.  However, this polymorphism is found in earlier human isolates.  They are specific for H2N2 from 1957 to 1968 and H3N2 from 1968 to 1976.  Another polymorphisms is also found in human isolates.  In addition to these two regional specific isolates are two more that a 5 bp apart (C2107T and C2112T).  These two polymorphisms are found in other isolates and all are H1N1.  These include the most recent H1N1 isolates on deposit at Los Alamos and extend back to 1934.  In addition there is one isolated from a 1998 Ontario mallard as well as a 1982 Mongolian camel.  Thus, although the two polymorphism and upstream sequence (18 BP probe) has been limited to H1N1 isolates, it is present on the same five Astrakhan H5N1 isolates that share polymorphism from North America.  The isolates with the paired PB1 polymorphism are listed below.

The acquisition of these human polymorphisms is cause for concern.  These acquisitions create longer regions of identity with human influenza sequences, which increase the likelihood of additional recombinations.  The acquisition of human polymorphisms in isolates from Vietnam and Thailand has been noted as have the acquisition of European swine sequences.

The acquisition of multiple human polymorphisms on PB1 and PB2 are cause for concern.

   DQ343505  A/Cygnus olor/Astrakhan/Ast05-2-2/2005  2005  H5N1   
   DQ363915  A/Cygnus olor/Astrakhan/Ast05-2-4/2005  2005  H5N1   
   DQ365008  A/Cygnus olor/Astrakhan/Ast05-2-5/2005  2005  H5N1   
   DQ365000  A/Cygnus olor/Astrakhan/Ast05-2-6/2005  2005  H5N1   
   DQ363920  A/Cygnus olor/Astrakhan/Ast05-2-7/2005  2005  H5N1   
   CY007473  A/Canterbury/106/2004                                 2004  H1N1   
   CY002990  A/New York/221/2003                                    2003  H1N1   
   CY002686  A/New York/222/2003                                    2003  H1N1   
   CY002694  A/New York/223/2003                                    2003  H1N1   
   CY002542  A/New York/227/2003                                    2003  H1N1   
   CY003302  A/New York/228/2003                                    2003  H1N1   
   CY002630  A/New York/230/2003                                    2003  H1N1   
   CY003382  A/New York/292/2003                                    2003  H1N1   
   CY003390  A/New York/293/2003                                    2003  H1N1   
   CY002710  A/New York/348/2003                                    2003  H1N1   
   CY006433  A/New York/350/2003                                    2003  H1N1   
   CY002814  A/New York/399/2003                                    2003  H1N1   
   CY008530  A/New York/483/2003                                    2003  H1N1   
   CY003694  A/New York/486/2003                                    2003  H1N1   
   CY006921  A/New York/488/2003                                    2003  H1N1   
   CY006673  A/New York/493/2003                                    2003  H1N1   
   CY003710  A/New York/496/2003                                    2003  H1N1   
   CY006201  A/New York/497/2003                                    2003  H1N1   
   CY002534  A/New York/220/2002                                    2002  H1N1   
   CY003310  A/New York/291/2002                                    2002  H1N1   
   CY006681  A/New York/494/2002                                    2002  H1N1   
   CY001958  A/New York/205/2001                                    2001  H1N1   
   CY002622  A/New York/208/2001                                    2001  H1N1   
   CY006425  A/New York/212/2001                                    2001  H1N1   
   CY003006  A/New York/239/2001                                    2001  H1N1   
   CY003014  A/New York/241/2001                                    2001  H1N1   
   CY006361  A/New York/242/2001                                    2001  H1N1   
   CY003022  A/New York/246/2001                                    2001  H1N1   
   CY002574  A/New York/281/2001                                    2001  H1N1   
   CY003318  A/New York/302/2001                                    2001  H1N1   
   CY006369  A/New York/303/2001                                    2001  H1N1   
   CY003398  A/New York/305/2001                                    2001  H1N1   
   CY003406  A/New York/306/2001                                    2001  H1N1   
   CY002806  A/New York/308/2001                                    2001  H1N1   
   CY006881  A/New York/309/2001                                    2001  H1N1   
   CY002678  A/New York/310/2001                                    2001  H1N1   
   CY002702  A/New York/312/2001                                    2001  H1N1   
   CY003030  A/New York/341/2001                                    2001  H1N1   
   CY003326  A/New York/342/2001                                    2001  H1N1   
   CY002398  A/New York/343/2001                                    2001  H1N1   
   CY006785  A/New York/344/2001                                    2001  H1N1   
   CY002406  A/New York/345/2001                                    2001  H1N1   
   CY003334  A/New York/346/2001                                    2001  H1N1   
   CY003470  A/New York/442/2001                                    2001  H1N1   
   CY003478  A/New York/443/2001                                    2001  H1N1   
   CY003294  A/New York/444/2001                                    2001  H1N1   
   CY003839  A/New York/445/2001                                    2001  H1N1   
   CY003486  A/New York/446/2001                                    2001  H1N1   
   CY006177  A/New York/447/2001                                    2001  H1N1   
   CY002646  A/New York/233/2000                                    2000  H1N1   
   CY002654  A/New York/234/2000                                    2000  H1N1   
   CY004513  A/mallard/Alberta/201/1998                          1998  H1N1   
   AF398865  A/Charlottesville/31/95                                   1995  H1N1   
   X66320       A/Chile/1/83                                                    1983  H1N1   
   M73973       A/camel/Mongolia/82                                     1982  H1N1   
   CY008994   A/Denver/57                                                    1957  H1N1   
   M25932       A/Beijing/11/56                                               1956  H1N1   
   X99037       A/Fort Monmouth/1/47                                    1947  H1N1   
   NC_002021 A/Puerto Rico/8/34                                        1934  H1N1   
   AF389116    A/Puerto Rico/8/34/Mount Sinai                  1934  H1N1  

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