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Paradigm Shift Intervention Monitoring
N158D Raises Pandemic Concerns
The above comments on N158D are true, but suggest that the acquisition in human cases in Egypt is relatively recent. However, N158D is widespread in clade 2.2 sequences and was present in initial wild bird sequences in Egypt isolated in late 2005 (A/teal/Egypt/14051-NAMRU3/2005) and early 2006, including the egret sequence (A/egret/Egypt/1162/2006) used by the CDC in their published H5N1 transmission studies.
The presence of N158D in the early wild bird and poultry isolates in Egypt led to human cases in the spring of 2006, and these sequences had N158D. As noted in the above quote, this presence has persisted and is seen in the most recent human public sequences from Egypt.
However, this acquisition was not limited to human H5N1 cases in Egypt. Clade 2.2 clusters and cases were also reported in Turkey, Iraq, and Djibouti in early 2006 and Nigeria in 2007. These human clusters / cases also had N158D (see list here).
Moreover, a 2.2 sub-clade maintained N at position 158, but had and A at position 160 which also abolished the glycosylation site at position 158. These sequences were found in human clusters and cases from Azerbaijain in 2006 and subsequent cases in Bangladesh (see list here).
Thus, the absence of a glycosylation site at position 158 is common in clade 2.2 and has been found in human cases since the first clade 2.2 cases were confirmed in early 2006.
Virtually all H5N1 cases in Turkey, Azerbaijan, and Iraq were in clusters which contained PB2 E627K in addition to the absence of a glycosylation site at position 158. Moreover, almost all had additional receptor binding domain changes including S227N in Turkey, Q196R in Iraq. The Iraq cases also had N186S, while the Azerbaijan cases had N186K. Thus, it is likely that these changes contributed to the formation of clusters, since N158D, Q196R and PB2 E627K have been cited as key changes in recent H5N1 transmission studies by Kawaoka, Fouchier, and the CDC.
Moreover, N158D is also circulating in recent clade 18.104.22.168 wild bird infections, as well as the recent case from Shenzhen (A/Guangdong-Shenzhen/1/2011), which also had S227R and Q196K.
Thus, N158D is associated with a range of human H5N1 cases that extend well beyond recent cases in Egypt.