H5N1 Recombination and Reassortment in Aswan Egypt
Recombinomics Commentary
March 21, 2007
NAMRU-3 has generated HA and NA sequences from the two recent confirmed cases in Aswan, Egypt. Although the two cases were admitted three days apart and the epidemiological evidence indicated they were not linked, the HA and NA sequences from the two patients (10F and 2M) differed by a single nucleotide, indicating they were infected by a common source.
The sequences had clear evidence for both ressortment and recombination. Both sequences were clade 2.2 with a number of Egyptian regional markers. The HA sequence had G186A, G496A, C661T, C727T, C779T, G878A, C937T, G1018T, C1261T, and C1618T. All of the 2006 and 2007 Egyptian H5N1 isolates have almost all of these markers. Similarly, the NA sequences have C150T, C236T, A703A, A740G, T1066C, G1280A, which are also markers which define Egyptian isolates.
However, the NA sequence found in both Aswan isolates (A/Egypt2321-NAMRU3/2007 and A/Egypt2331-NAMRU3/2007), have a number of additional markers found in two recent isolates in Beni Suef (A/Egypt/0636-NAMRU3/2007) and Fayyoum (A/Egypt/1394-NAMRU3/2007), C157A, T173C, G377A, C854A, C976T. These sub-regional markers link the NA sequences from these recent cases in central and southern Egypt.
The HA sequences are quite distinct. The two sequences from central Egypt share a 3 BP deletion, as well as A203G, C394T, G435A, T528C, A913G, A1603G. In contrast, the two sequences from southern Egypt share G82A, G118A, A356G, C449T, G469T, C499A, G536A, A587A, C642T, C736T, A830T, G907A, A1059G, C1614T.
The sequences of the additional six gene segments will further define the reassorted gene segments, but the similarities in the NA sequences and the differences between the HA sequences provide clear evidence for reassortment.
The sequences also have evidence for recombination. The HA sequences from central Egypt have a 3 BP deletion that matches H5N1 chicken isolates from Hunan. Thus, the 3 BP deletion is appended to the Egyptian Qinghai genetic background. Similarly, the HA sequences from southern Egypt have the novel cleavage site found in whooper swans in Mongolia.
The evidence of both reassortment and recombination the recent cases from central and southern Egypt highlight genetic exchanges via dual infections. The widespread dual infections is supported by additional sequences with mixed signals in both human and poultry isolates.
The latest sequences highlight the overlapping flyways that cover Egypt which leads to frequent dual infections and rapid H5N1 evolution.
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