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H7N9 Human PB2 Changes Raise Pandemic Concerns
Recombinomics Commentary 20:00
April 22, 2013

Hangzhou Center for Disease Control and Prevention released three sets (H7, N9, PB2) of sequences (at GISAID) from two patients in Hangzhou (67M – A/Hangzhou/2/1013 and 79M – A/Hangzhou/3/2012) as well as a fecal environmental sample, A/Environment/Hangzhou/34/2013 (see map), and they are to be commended for the rapid release of these important sequences. 

All of the sequences were closely related to recent H7N9 sequences from the Shanghai area and all had H7 Q226L.  However, as seen in prior sequences, both of the human sequences had a change in PB2 that has been associated with mammalian adaptation, which for the above two cases was E627K.  Similarly, as seen in prior avian sequences, the PB2 was wild type at positions 627 and 701 for the environemntal sample.

The presence of PB2 E627K or D701N in all 7 human PB2 sequences and the absence the polymorphisms in the 5 avian sequences raises concerns that the human cases are not due to avian sequences which lack those polymorphisms.  However, E627K is present in waterfowl infected with clade 2.2 H5N1 bird flu and E627K has also been identified in an H7N9 wild bird sequence from South Korea, A/wild bird/Korea/A3/11, raising the possibility that waterfowl are linked to the human cases.
However, that linkage may be indirect and involve a mammalian intermediate, such as swine, canine, or feline or simply involve human to human transmission, which is largely missed because of limited testing of mild cases.

All of the seven human sequences released to date have been from fatal or critical cases, so the presence of absence of PB2 E627K or D701N in mild cases is unclear. 

Release of PB2 sequences fro milder cases would be useful.

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