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Field Experiment On H7N9 Human Adaptation
Recombinomics Commentary 21:00
April 6, 2013

The release of H7N9 sequences by Hangzhou Center for Disease Control and Prevention yesterday clearly demonstrated the continuing human adaptation of H7N9.  Less than a week ago the WHO Chinese Influenza Center has released full sequences from the first three confirmed H7N9 cases, and those sequences also demonstrated human adaptation involving the same changes linked to H5N1 bird flu transmission experiments.  However, unlike the H5N1 experiments where all three research labs added Q226L to the H5 under study because the polymorphisms had never been reported in a natural H5 or H7 isolate, the polymorphism was present in the two more recent sequences released last Sunday, which were from human isolates.

The acquisitions in the human sequences matched most of the key changes in the H5N1 studies.  All three labs added two receptor binding domain changes to the H5 under study.  Two labs (CDC and EMC) added Q226L and G228S, while the third lab (University of Wisconsin) added N224K and Q226L.  Similarly, all three used a PB2 that was adapted to mammals.  The two labs using an avian PB2 either used a natural human isolate with E627K or added E627K to a human sequence.  The third lab used an H1N1pdm09 genetic background which had a mammalian adapted PB2.  Moreover, all experiments ended with an H5 that had abolished the glycosylation site at position 158.  The CDC started with an H5 from an egret in Egypt, which had abolished the site, while the other two labs passage their H5 through ferrets which abolished the glycosylation site.

All four of the H7N9 sequences had the position 158 glycosylation site abolished, as well as a PB2 with E627K (confirmed in the first three cases and assumed for the fourth case, since the PB2 sequence wasn’t released).  The earliest case, A/Shanghai/1/2013 was wild type at position 226.  The second, A/Shanghai/2/2013, and third, A/Anhui/1/2013 had Q226L (due to A704T), which was used by all three labs.  The fourth case A/Hangzhou/1/2013 added yet another nucleotide change (C703A) to produce L226I, which is in current H3N2 seasonal flu.

Thus, the four human H7N9 sequences demonstrated rapid human adaptation, but the adaptation was accomplished by passing H7N9 through humans in an uncontrolled field experiment, which is clearly hazardous to the world’s health.

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