Recombinomics: Adaptation of Egypt H5N1 Toward Human Transmission

May 1, 2012 The National Laboratory for Veterinary Quality Control on Poultry Production has released twenty H5 poultry sequences (at Genbank) from samples largely collected in late 2011 / early 2012. All except A/chicken/Egypt/113Q/2011, which was collected on July 26, 2011 had the 3 BP deletion, S133del. Thus, the deletion, which is a hallmark of clade 2.2.1 G, is in all samples collected in late 2011 or 2012. This dominance of clade 2.2.1 G in poultry in Egypt matches the results reported for human isolates.

Although NAMRU-3 has not released H5 sequences from human cases in Egypt since 2010, all sequences after mid-2009 were clade 2.2.1 G. Similarly, WHO phylogenetic trees of the withheld sequences from cases in 2011 were also clade 2.2.1 G, strongly suggesting that all 2011 human cases also had the 3BP deletion.

This sub-clade has also been noted for similarities with seasonal H1N1, raising concerns of adaptation to human transmission. This adaptation was also seen in CDC studies on H5N1 transmission in a ferret model. Their published studies used a 2006 egret isolate, A/egret/Egypt/1162/2006, which had N158D. The CDC study demonstrated transmission without isolation of variants that arose via ferret transmission.

Transmission studies by Kawaoka noted the selection of N158D in the clade 2.3.4 isolate, A/Vietnam/HN31604/2009, used in those studies.

Similarly, comments by Fouchier strongly suggested that N158D was also selected during passage in ferrets of a clade 2.1 isolate from Indonesia, A/Indonesia/5/2005.

The Kawaoka study also started with a receptor binding domain change, N224K, which has been identified in a clade 2.2.1 G isolate in Egypt, A/duck/Egypt/10185SS/2010 . However, this change is not present in the 20 recently released sequences.

The dominance of clade 2.2.1 G also reduces concerns regarding Q196K, which is present in clade 2.2.1 F (including the one released sequence, A/chicken/Egypt/113Q/2011, noted above). The CDC used the related change Q196R in their transmission studies.

Similarly, the acquisition of H1N1pdm09 and seasonal H1N1 sequences in PB2 and PB1 were present in clade 2.2.1 F sequences, but the number of internal gene sequences from Egypt samples is very limited and virtually absent for the human cases, so the presence of similar recombination events in additional poultyry and human isolates is unclear.

Thus, the latest samples confirm the dominance of clade 2.2.1 G in poultry and human cases in Egypt, which has multiple changes associated with human adaptation and transmission, which is cause for concern.