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Egypt H5N1 PB1 Recombination With H1N1pdm09
Recombinomics Commentary 10:30
January 17, 2012

The recently released H5N1 sequences from Egypt have clear examples of recombination in PB1 and PB2 involving seasonal and pandemic acquisitions.  These isolates were discussed last year in the PLOS paper “The Epidemiological and Molecular Aspects of Influenza H5N1 Viruses at the Human-Animal Interface in Egypt” which briefly discussed the sequences and provided Genbank accession numbers.  However, the sequences were not released until last week. 

The paper included a phylogenetic tree for the HA genes, which were similar to other public H5N1 clade F sequences from Egypt, which are vaccine resistant.  The paper also discusses human H5N1 in Egypt, which have been clade G (since mid-2009).  However, there have been no human H5N1 sequenced from Egypt since March, 2010.  At that time most of the cases were mild and in children, which lowered the cases fatality rate in Egypt to less than 10%.  The cases with the 3 BP deletion had an bioinformatic profile which has similar to seasonal H1N1 and the 3 BP deletion (133del) was also found in H5N1 sequences in China and Indonesia (see slide 12 from OneHealth workshop; labeled as 133del in clade C).However, more recent cases have been in adults and fatal, raising concerns that the more recent cases involve the vaccine resistant clade F.

The PB1 sequence has clear evidence of recombination.  Two of the isolates described in the above paper and displayed on the HA tree were A/chicken/Egypt/Q1011/2010 and A/chicken/Egypt/Q1185/2010 had identical HA sequences, which was also true for the newly released PB1 sequences for Q1011 and Q1185.  However, the first 60 nucleotide are identical to H1N1pdm11.  The H5N1 sequence for closely related sequences, including the two most closely related sequences in the above paper (A/chicken/Egypt/1/2009 and A/chicken/Egypt/Q1182/2010), have 8 differences, clustered between positions 15 and 53 (T15C, T24C, G26A, G30A, A32T, T37C, T47C, T53C), clearly signal homologous recombination between PB1 H5N1 and H1N1pdm11.

This recombination is also supported by the PB2 sequences, which have additional examples of recombination with H1N1pdm09 sequences as well as seasonal H1N1 and H3N2 sequences, raising concerns of human adaptation. 

Moreover, the first 60 nucleotides of A/chicken/Egypt/Q1182/2010 and A/chicken/Egypt/Q1185/2010 exactly match recent H3N2v sequences from Indiana (A/Indiana/08/2011 and A/Indiana/10/2011) and Pennsylvania (A/Pennsylvania/09/2011 and A/Pennsylvania/11/2011).

Therefore, NAMRU-3 and/or the US CDC, who receives samples from NAMRU-3, should immediately release full sequences for human H5N1 cases in Egypt.

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