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Paradigm Shift Intervention Monitoring
Q196K and S227R
In Fatal H5N1
Case In Shenzhen China
The WHO Chinese National Influenza Center is congratulated for its rapid release of these important sequences.
The HA sequence has several receptor binding domain (RBD) changes, including S227R, which had been reported previously in wild birds in Hokkaido and Fukushima, Japan raising transmission concerns, as seen in S227N in Hong Kong and Turkey. In addition, the sequence has Q196K, which has been reported in vaccine resistant H5N1 in Egypt. Q196R has been reported in an H5N1 cluster in Iraq. These RBD chnages are in addition to V223I and M230I seen in prior clade 18.104.22.168 isolates from wild birds as well as 2010 H5N1 cases in Hubei, A/Hubei/1/2010, and Hong Kong, A/Hong Kong/6841/2010. H5N1 also has D225G, which targets the lung.
Moreover, although the sequence is clade 22.214.171.124, the HA cleavage site has acquired an R to yield IERRRKR.
These changes raise serious transmission issues. Release of the PB2 sequence and status of position 627 would be useful.