M230I Convergence in Qinghai H5N1 in Egypt
Recombinomics Commentary
January 29, 2007
Recently NAMRU-3 has released HA sequences from fatal H5N1 infections in Egypt this season. The initial sequence was from an infection in Gharbiya in October and contained a change, M230I, adjacent to the receptor binding domain. This change had not been previously reported in H5N1 Qinghai isolates. However, it is present is all three human seasonal strains, H3N2, H1N1, and influenza B. Moreover it creates a five amino acid match with influenza B at positions 226-230 (QSGRI). M230I is also in other serotypes involved in transmission between mammals. It is in H3N8 found in horses and dogs. Moreover it is in recent H7 outbreaks in the Netherlands (H7N7), Canada (H7N3), and England (H7N3) that were associated with transmission to humans. These outbreaks were likely due to wild birds.
In December Egypt reported an H5N1 cluster in Gharbiya. The family lived 12 miles from the first case and all three infected family members died. Sequences from two of the cluster members were released. The HA sequences also had M230I and the NA sequences had the Tamiflu resistance marker N294S.
To determine the origin of the newly introduced M230I, H5N1 HA sequences were generated by NAMRU-3 from poultry from backyard farms in Menoufeya, Beni Suef, Gharbiya, and Damietta, and a commercial poultry facility in Fayoum. All isolates except Beni Suef had M230I. However, only the isolate from Damietta had G754A. The other three isolates had G754T, which was present in the H7N3 outbreak in England in 2006.
Thus, two different codons for M230I converged in the Egypt. One had been reported previously in H5N1 in Asia. This codon was in all the Gharbiya human sequences. The other codon was in H7N3 isolates from England, which were also thought to be transported by wild birds.
The convergence of two different codons for M230I in Qinghai H5N1 in Egypt is curious. The new acquisitions were on a Qinghai Egyptian genetic background, yet they traced back to distinct H5N1 or H7N3 isolates. The acquisitions are most easily explained by recombination. The convergence of M230I may signal a mammalian intermediary because of the linkage of M230I to serotypes that are linked to mammal -to-mammal transmission. Moreover, M230I may be transported downstream to Djibouti and Sudan in eastern Africa, as well as countries in western Africa, such as Nigeria and Ivory Coast, which have had recent H5N1 Qinghai outbreaks.
In Egypt, the acquisition of mammalian polymorphisms in association with Tamiflu resistance remains a cause for concern.
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