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Commentary

Alberta ex-Beijing H5N1 Has RBD Change D225R
Recombinomics Commentary 02:30
January 25, 2014

The Health Protection Agency of Canada (HPAC) has released (at GISAID) a  full set of sequences, A/Alberta/01/2014, from the nurse who developed symptoms while returning to Canada from a trip to Beijing.  The HPAC is to be acknowledged for the rapid release of these important sequences.  The isolate was a recombinant with 7 of the 8 gene segments related to clade 2.3.2 waterfowl sequences in Vietnam, as well as wild birds isolates from a broad geographic range in eastern Asia.  The PB2 however is closely related to H9N2 poultry sequences circulating in northern China.

Moreover, the H5 sequence is also related to for isolates from northern China, a tiger isolate from Jiangsu, A/tiger/Jiangsu/01/2013, as well as three environmental sequences from sewage in Huzhou (A/Environment/Huzhou/C291-6/2013, A/Environment/Huzhou/C291-7/2013, and A/Environment/Huzhou/C291-10/2013).

The H5 sequence also had two receptor binding domain changes, R193K and D225R.  The D225R change is a particular interest, because most H5N1 sequences have D225G, which targets the lungs, but the fatal infection in the Alberta nurse presented as encephalitis and without a cough.  The sequence from Canada was from a cloned isolate, which was presumably from mammalian cells, which would have selected against D225G.  However, D225R has been reported in H5N1 bird flu from a duck in Hunan, A/duck/Hunan/15/2004, and may be responsible for neurological targeting instead of lower respiratory tract.

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