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Commentary

Egypt H5N1 PB2 H1N1pdm09 and Seasonal H1N1 Recombination
Recombinomics Commentary 23:45
January 17, 2012

All the amino acid sequences of the Egyptian strains (both from the present study and publically available in GenBank as of June 1st 2010) from 2006 to 2010 had a lysine at position 627 in PB2, a marker for enhanced virulence of influenza viruses in mammals [14], except for A/chicken/Egypt/Q1182/2010 which had a glutamic acid at residue 627.
 
The above comments from the PLOS paper, “The Epidemiological and Molecular Aspects of Influenza H5N1 Viruses at the Human-Animal Interface in Egypt” note the absence of PB2 E627K in one of the H5N1 isolates, A/chicken/Egypt/Q1182/2010.  The sequences from this isolate were recently released at Genbank, and the PB2 sequence is a recombinant between multiple parental sequences, which are dominated by pH1N1[dm09 and seasonal H1N1.  A BLAST result, which returns the most closely related sequences, is composed of H1N1pdm09 for the 100 most closely related sequences.  However, there are a large number of non-synonymous changes, listed below.  The changes are clustered in the-amino portion of the protein (between positions 64 and 478  which match seasonal H1N1 sequences.  The carboxyl end of the protein is H1n1pdm09, which has an E at position 627, as noted above.
In addition to the H1N1pdm09 and seasonal H1n1 sequences in the above isolate, two other sequences, A/chicken/Egypt/Q1185/2010  and A/chicken/Egypt/1011/2010 also have H1N1pdm09 on an H5N1 background, signaling additional recombination in PB2.

These two isolate also have H1N1pdm09 sequences in the PB1 gene, signaling additional recombination with H1N1pdm09.

The presence of recombined H1N1pdm09 in multiple H5N1 isolates in Egypt raises concerns that similar sequences are in human H5N1 cases, which have recently been lethal and linked to clusters.

Full sequences from human sequences in Egypt should be released by NAMRU-3 and/or US CDC immediately.

PB2 polymorphisms
 
M64T
D65E
T81M
A83T
A98S
G225S
V292T
I315M
K340R
I354L
R355T
R368K
I411V
Q447L
S453H
L475M
I478V

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