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Paradigm Shift Intervention Monitoring
2011 Human H5N1
Sequence Cluster In Egypt
One sequence cluster is created by A/Egypt/N0544/2011, A/Egypt/N6774/2011, A/Egypt/N7724/2011, which includes an isolate from the beginning of 2011 as well as two collections from the spring / summer.
These three human sequences are on a branch which includes two poultry sequences, A/chicken/Egypt/11506sf/2011 and A/chicken/Egypt/VIR4453-138/VRLCU/2011. The sequence for the latter is at GISAID and the H5 sequence has two recently acquired non-synonymous changes (R143K and D454N), which are unlikely to significantly affect receptor binding. However, this clustering of sequences from samples collected over a long time frame in 2011 raises concerns that this sub-clade is transmitting human to human.
This concern is increased by 2010 poultry sequences which have recombined PB1 and PB2 which have acquire H1N1pdm09 and seasonal H1N1 sequences. The most recent human H5N1 sequences from Egypt were the 19 released by NARMRU-3 almost 2 years ago. However, only HA and NA sequences were released. The most recent internal gene sequences from cases in Egypt are from 2006.
The recent H5N1 transmission paper by the CDC used an Egypt H5 (from a 2006 isolate from an egret, A/egret/Egypt/1162/2006). The current human sequences in Egypt have the 3 BP deletion and similarities with seasonal H1N1, and therefore may transmit more easily than the egret sequence. Similarly, the delayed Kawaoka paper uses H5 on a background with H1N1pdm09 genes, raising concerns that PB1 and PB2 sequences which have recombined with H1N1pdm09 and seasonal H1N1 may transmit more efficiently.
Thus, full sequences from human H5N1 cases should be released immediately by NARMU-3 and/or the CDC.