Egypt Qinghai H5N1 More Complex in 2007
Recombinomics Commentary
May 1, 2007
Ten HA sequences from patients in Egypt were released today at Genbank (see list below). All 10 are from patients diagnosed this year and the sequences highlight the increased genetic complexity of H5N1 in Egypt. The sequences, generated by US NAMRU-3 were presented at the Northern California ASM (NCASM) spring meeting at the end of March. The added complexity can be seen in the table of HA polymorphisms (here) as well as the HA phylogram here.
As described previously, the samples from southern Egypt (Aswan and Mena), have the novel Mongolian HA cleavage site. Four of these sequences (2321, 2331, 2616, and 2620) became public today and they can be seen in a separate branch along with 2750 (which has not yet been made public).
Similarly, two additional sequences (1394 and 2621) have the same 3 BP deletion seen in the previously released sequence, A/Egypt/0636-NAMRU3/2007, from the patient in Beni Suef. These sequences form another branch on the tree. One is the older sibling from the family cluster in Qena. Other sequences on the same branch include the younger sibling, A/Egypt/2629-NAMRU3/2007, as well as A/Egypt/2631-NAMRU3/2007 from Qalubiea. Both of these also have the same 3 BP deletion. As noted earlier, this deletion is an exact match of the deletion in 2006 chicken isolates from Hunan. However, as seen in the phylogenetic tree as well as the table of HA Egyptian polymorphisms, these sequences have the Qinghai and Egyptian markers found in the other isolates from Egypt. This acquisition of the 3 BP deletion in the Egyptian isolates creates significant problems for the more traditional explanation of H5N1 evolution, which relies on random mutation, since 3 BP deletions are rare, and these recent Egyptian isolates have the same deletion seen in China, on a very different genetic background.
The NA sequences from the isolates were also presented at the NCASM meeting and the polymorphisms are in the table here, as well as the phylogenetic tree here. The NA phylogram has the same branching seen in the HA phylogram and the branches are created by sequences from the same isolates. Two of the isolates that have the 3 BP deletion in HA have NA G743A (marked with arrows). This polymorphism was seen in a subset of isolates from Germany last year (marked with a bar). The Egyptian isolates have this polymorphism, but lack the other regional markers seen in Germany, which puts the German isolates on another branch.
The acquisition of G743A by the siblings from Qena creates another problem for the random mutation explanation, because the change is at the tip of the branch, and not found in the earlier isolates with the 3 BP deletion. Similarly, this change is found in recent bird isolates from Gharbiya, which are on two other branches, as well as the recent isolate from Sohag, A/Egypt/2630-NAMRU3/2007, which creates similar problems for a random mutation explanation.
Thus, the newly released sequences confirm earlier analysis, which describes the added genetic complexity of the H5N1 isolates from Egypt, which raises serious questions about models which rely on random mutations to explain the evolution of H5N1.
Released sequences
A/Egypt/1394-NAMRU3/2007(H5N1)
A/Egypt/1604-NAMRU3/2007(H5N1)
A/Egypt/1731-NAMRU3/2007(H5N1)
A/Egypt/1902-NAMRU3/2007(H5N1)
A/Egypt/2256-NAMRU3/2007(H5N1)
A/Egypt/2321-NAMRU3/2007(H5N1)
A/Egypt/2331-NAMRU3/2007(H5N1)
A/Egypt/2616-NAMRU3/2007(H5N1)
A/Egypt/2620-NAMRU3/2007(H5N1)
A/Egypt/2621-NAMRU3/2007(H5N1)
Media sources
Recombinomics Presentations