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N186S and Q196R In Iraq H5N1 Patients

Recombinomics Commentary
December 1,  2006

Recently, human H5N1 sequences from patients in Iraq were released from the WHO private database of H5 sequences.  The five sequences were generated by Weybridge and are listed below. 

Recently, a paper in Nature described HA changes that enhanced binding to 2,6 gal receptors which are found in the upper respiratory tract of humans.  Increases in affinity for these receptors are likely to lead to enhanced human-to-human transmission.  The paper focused on changes in H5N1 human isolates from Vietnam and Thailand.  Two of the changes, N186K and Q196R were said to be in human isolates from 1 case in Iraq and 2 cases in Azerbaijan.  However, it was unclear if both changes were in isolates from the same individual(s), or separate individual(s).

The data could not be independently confirmed beyond WHO consulting scientists because the human sequences were not public.  However, the recent release of human sequences from Iraq and Azerbaijan identifies these changes as being in separate cases.

However, N186S was present in the public human sequence from Iraq, but not in the goose or cat isolates.  This change is also in all five additional human sequences from Iraq.  In addition, two of the released sequences, A/Iraq/659/06 and A/Iraq/756/06, have Q196R.  It is unclear if these two sequences, which are closely related to each other, are from the same individual. 

Usually, multiple isolates from the same host isolated by the same lab have samples numbers in common.  These two sequence numbers, 659 and 756, are distinct.  The source of the five human sequences from Weybridge is also confusing because there are only three confirmed Iraq cases listed by WHO.  None of the sequences from Weybridge have age or gender indications in the associated characterization sheet. 

The characterization sheet associated with the human sequence isolated by US NAMRU3, A/human/Iraq/207-NAMRU3/2006, appears to be from the index case, because it is from a 15F.  However, that sequence is distinct from the five sequences from Weybridge, including A/Iraq/1/2006.  Two other human sequences from Weybridge, A/Iraq/754/06 and A/Iraq/755/206 are closely related to each other, but even if the two sets of closely related sequences are from the same individual, there would still be four distinct human sequences, while there are only three confirmed cases from Iraq.

Information on the relationship of the six human sequences from Iraq to the three confirmed cases in Iraq would be useful.

New Releases

ISDN140053  A/Iraq/1/2006    2006   H5N1 
ISDN140059  A/Iraq/659/06    2006   H5N1   
ISDN140060  A/Iraq/754/06    2006   H5N1   
ISDN140052  A/Iraq/755/2006 2006  H5N1   
ISDN140061  A/Iraq/756/06    2006   H5N1  

Prior Releases

DQ435202  A/Iraq/207-NAMRU3/2006            2006  H5N1
DQ435200  A/domestic cat/Iraq/820/2006       2006  H5N1 
DQ435201  A/domestic goose/Iraq/812/2006  2006  H5N1   

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