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G228S Acquisition Via Avian H5N1 - Swine H1N1 Recombination

Recombinomics Commentary

February 16, 2006

The recent reports of H5N1 throughout Europe raise concerns of recombination between H5N1 migrating into the region and other sero-types indigenous to the region.  In the fall, H5N1 migrated into the Middle East.  The presence of those new H5N1 sequences offered the opportunity of recombining with H9N2 in domestic poultry.  The presence of donor sequences in H9N2 in the Middle East led to a warning of more efficient transmission of H5N1 via the acquisition of S227N. 

The Qinghai version of H5N1 was responsible for the large die-off of waterfowl at Qinghai Lake in May, 2005.  The sequences isolated from dead birds, primarily bar-headed geese, contained sequences of a recombinant H5N1 with a genetic background similar to H5N1 isolates in Asia.  However the Qingahi H5N1 contained unique polymorphisms found primarily in Europe, including PB2 sequences that matched European swine.  The PB2 sequences also had E627K, a polymorphism that had not previously been reported in H5N1 from birds.  This polymorphism is found in all human H1, H2, and H3 isolates, including the 1918 pandemic strain.

The Qinghai strain was subsequently identified in Novosibirsk, Mongolia, Kazakhstan and subsequently in regions to the west such as Tula, Volga Delta, Romania, Croatia, and western Turkey.  However, none of these H5N1 isolates were linked to confirmed human cases.  However, human cases were reported in eastern Turkey at the end of December. S227N was identified in H5N1 from the index case.  The index case was part of a very large cluster, involving at least three families.  Sixteen family members were hospitalized and seven were confirmed to be H5N1 positive.  Four of the seven died.

The new reports of H5N1 in Europe, as well as the East Atlantic Flyway in Nigeria, raise concerns that large numbers of H5N1 infected birds will be migrating into and through central and western Europe.  S227N has been shown to increase the affinity for human receptors, which was the basis of the October 22 warning.

Prior studies have shown that a polymorphism at the adjacent position, G228S, also increases the affinity for human receptors, which would lead to increased efficiency of H5N1 infections of humans.  Analysis of the Loa Alamos or Genbank influenza sequences on deposit has identified donor sequences in swine in Europe.  All are H1, and all but one is H1N1.  The isolates with appropriate donor sequences for acquisition of G228S are listed below.

Since recombination between H5N1 can lead to the acquisition of G228S, there is cause for concern that the resulting recombinant would have increased affinity for human receptors, leading to more efficient transmission.

The isolates with the appropriate donor sequences are:

   AJ517815  A/Switzerland/8808/2002                 2002  H1N1  
   AJ517820   A/swine/Cotes d'Armor/736/2001  2001  H1N1   
   AJ517818   A/swine/Italy/10951/2001                2001  H1N1   
   AJ517817   A/swine/Italy/13260/2001                2001  H1N1   
   AJ412708   A/swine/Cotes d'Armor/1121/00    2000  H1N1   
   AJ344004   A/swine/Cotes d'Armor/918/00      2000  H1N1   
   AJ517819   A/swine/Italy/3088/00                      2000  H1N1   
   AJ344018   A/swine/Italy/3364/00                      2000  H1N1   
   AJ344021   A/swine/Cotes d'Armor/1455/99   1999  H1N1   
   AJ412711   A/swine/Cotes d'Armor/1482/99   1999  H1N1   
   AJ412712   A/swine/Cotes d'Armor/1488/99   1999  H1N1   
   AJ344002   A/swine/Cotes d'Armor/1515/99   1999  H1N1   
   AJ344013   A/swine/Italy/2064/99                      1999  H1N2   
   AY590824  A/swine/Belgium/1/98                      1998  H1N1   
   AJ344016   A/swine/Italy/1511/98                      1998  H1N1   
   AJ344020   A/swine/Italy/1589/98                      1998  H1N1   
   AJ344019   A/swine/Italy/1498-2/97                   1997  H1N1   
   AJ344017   A/swine/Italy/1509-6/97                   1997  H1N1   
   AJ344008   A/swine/Italy/1456-1/96                   1996  H1N1   
   AF320064  A/Swine/Netherlands/609/96          1996  H1N1   
   AJ344009   A/swine/Italy/1390-5/95                   1995  H1N1   
   AJ344011   A/swine/Italy/France/2111/95          1995  H1N1   
   AF320059  A/Swine/France/525/94                    1994  H1N1   
   AF320063  A/Swine/Netherlands/1743/93         1993  H1N1   
   AF320066  A/Swine/Netherlands/477/93           1993  H1N1   
   U72669       A/Swine/Schleswig-Holstein/1/93   1993  H1N1   
   U72667       A/Swine/England/195852/92           1992  H1N1   
   Z46435       A/swine/Schleswig-Holstein/1/92     1992  H1N1   
   Z46434       A/swine/Germany/8533/91               1991  H1N1   
   AF091315  A/Swine/Italy-Virus/671/87                1987  H1N1   
   AF320062  A/Swine/Netherlands/1/87                 1987  H1N1   
   AF320065  A/Swine/Netherlands/386/86            1986  H1N1   
   AF320056  A/Swine/France/3614/84                   1984  H1N1   
   AJ344015   A/swine/Finistere/2899/82                1982  H1N1  


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