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Efficient Human to Human Transmission Via H5N1 / H9N2 Recombination

Recombinomics Commentary

October 22, 2005

In the upcoming Virology paper "Evolution of the receptor binding phenotype of influenza A (H5) viruses, Gambaryan et al screen H5 isolates for affinity for human Sia2-6Gal (human-like) receptors.  Two isolates, A/Hong Kong/212/2003 and A/Hong Kong/213/2003 were identified.  Both isolates had the S227N polymorphism. 

These two isolates were from bird flu patients who had returned from a visit to Fujian province,  The daughter had died in China with bird flu symptoms.  The two isolates were from her brother and father.  The father subsequently also died.  Thus, the change in receptor binding was associated with a familial cluster that probably involved human to human transmission.

Although the S227N change requires a simple G/A transition, it is rare.  This is similar to another polymorphism E627K in PB2.  The change is also encoded by a A/G transition, but is strictly conserved.  E was exclusively in avian H5N1 isolates and K was found in all human isolates.  The conservation could be explained by selection which may have been further restricted by opportunities for recombination.  The conservation was broken at Qinghai Lake, where all 16 avian isolates contained the human E627K polymorphism.

Similarly, the lack of S227N in H5N1 may be related to a lack of recombination opportunities.  As H5N1 expands its global reach via spread by long range migratory birds, the potential for new recombination targets generating novel genetic changes increases.

A search of the Los Alamos flu database using a 10 nucleotide probe representing the S227N polymorphism identified 42 exact matches.  All were in HA and all isolated after 1998 were in the Middle East in chickens, turkeys, geese, and an ostrich.

H9N2 has become endemic in Israel and millions of migratory birds will be passing through the area in the upcoming days.  Thus, the potential for dual infections by H9N2 and H5N1 is high.  The 10 nucleotides of identity offers an opportunity for homologous recombination that would create the S227N polymorphism and increase the efficiency of H5N1 human transmission.

Efforts to limit the exposure of  H9N2 infected birds to H5N1 infected wild birds should be aggressively pursued.

Isolates with donor sequences for S227N acquisition:

   AY575869  A/Hong Kong/212/03                                    2003  H5N1   
   AB212054  A/Hong Kong/213/03                                    2003  H5N1   
   ISDN38262 A/Hong Kong/213/2003                               2003  H5N1   
   AY575870  A/Hong Kong/213/2003                                2003  H5N1   
   AY738456  A/ostrich/Eshkol/1436/03                              2003  H9N2   
   DQ104453  A/turkey/Avigdor/1209/03                            2003  H9N2   
   DQ104454  A/turkey/Avigdor/1215/03                            2003  H9N2   
   DQ104458  A/turkey/Brosh/1276/03                               2003  H9N2   
   DQ104455  A/turkey/Kfar Warburg/1224/03                  2003  H9N2   
   DQ104464  A/chicken/Kfar Monash/636/02                   2002  H9N2   
   DQ104450  A/turkey/Avichail/1075/02                            2002  H9N2   
   DQ104473  A/turkey/Beit HaLevi/1009/02                     2002  H9N2   
   DQ104451  A/turkey/Ein Tzurim/1172/02                       2002  H9N2   
   DQ104462  A/turkey/Givat Haim/622/02                        2002  H9N2   
   DQ104471  A/turkey/Givat Haim/868/02                        2002  H9N2   
   AY548507  A/turkey/Givat Haim/965/02                         2002  H9N2   
   AY738452  A/turkey/Givat Haim/965/02                         2002  H9   
   DQ104459  A/turkey/Kfar Vitkin/615/02                         2002  H9   
   AY548510  A/turkey/Kfar Vitkin/615/02                          2002  H9N2   
   DQ104460  A/turkey/Kfar Vitkin/616/02                         2002  H9   
   AY548511  A/turkey/Kfar Vitkin/616/02                          2002  H9N2   
   AY548512  A/turkey/Mishmar Hasharon/619/02           2002  H9N2   
   DQ104461  A/turkey/Mishmar Hasharon/619/02          2002  H9   
   DQ104449  A/turkey/Naharia/1013/02                           2002  H9N2   
   DQ104452  A/turkey/Sapir/1199/02                               2002  H9N2   
   DQ104463  A/turkey/Yedidia/625/02                             2002  H9   
   AY548513  A/turkey/Yedidia/625/02                              2002  H9N2   
   DQ104448  A/turkey/Yedidia/911/02                             2002  H9N2   
   AY548514  A/chicken/Tel Adashim/786/01                   2001  H9N2   
   AY738454  A/chicken/Tel Adashim/786/01                   2001  H9   
   DQ104465  A/chicken/Tel Adashim/809/01                  2001  H9   
   AY548515  A/chicken/Tel Adashim/809/01                   2001  H9N2   
   AY548500  A/chicken/Tel Adashim/811/01                   2001  H9N2   
   DQ104467  A/chicken/Tel Adashim/811/01                  2001  H9   
   AY548501  A/chicken/Tel Adashim/812/01                   2001  H9N2   
   DQ104468  A/chicken/Tel Adashim/812/01                  2001  H9   
   DQ104469  A/goose/Tel Adashim/829/01                     2001  H9N2   
   DQ104470  A/goose/Tel Adashim/830/01                     2001  H9N2   
   AY548499  A/turkey/Givat Haim/810/01                         2001  H9N2   
   DQ104466  A/turkey/Givat Haim/810/01                        2001  H9   
   DQ104472  A/chicken/Maale HaHamisha/90658/00   2000  H9N2   
   AY738451  A/turkey/Neve Ilan/90710/00                        2000  H9   
   AY548502  A/turkey/Neve Ilan/90710/00                        2000  H9N2   
   AF218108  A/Peking Duck/Malaysia/F20/1/98             1998  H9N2   
   AF218105  A/Peking Duck/Singapore/F91-5/9/97       1997  H9N2   
   AY206675  A/quail/Hong Kong/A28945/88                    1988  H9N2 


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