PB2 D701N in H7N9 Zhejiang Critical Case

Recombinomics Commentary 22:45
April 19, 2013

State Key Laboratory of Diagnosis and Treatment of Infectious Diseases at The First Affiliated Hospital, College of Medicine, Zhejiang University has released full H7N9 sequences of an April 3 collection from a male patient in Zhejiang Province, A/Zhejiang/DTID-ZJU01/2013  The H7 sequence is an exact match with A/Anhui/1/2013.

n contrast to the four prior human sequences, (A/Shanghai/1/2013, A/Shanghai/2/2013, A/Anhui/1/2013,  A/Hangzhou/1/2013), the Zhejiang PB2 sequence does not have E627K.  However, the PB2 sequence does have D701N, which also enhances transmisison in mammls,
as seen in H5N1 transmission experiments. 

D701N It has also been seen previously in mammalian (human and tiger) H5N1 isolates, equine (H3N8 and H7N7), canine (H3N8), fatal infections in harbor seals (H3N8), novel H1N1v in Switzerland, human H9N2, and various swine serotypes as well as H7N7 avian sequences from the 2003 outbreak in the Netherlands, which generated an large number of human infections..

Thus, the presence of D701N signals mammalian adaption, and all human H7N9 PB2 sequences have an adaption (E627K or D701N), which has not been seen in any of the H7N9 poultry isolates, including the recent sequence from the Zhejiang H7N9 bird flu isolate, A/chicken/Zhejiang/DTID-ZJU01/2013.
The PB2 adaptations (E627K or D701N) in the human isolates, and the absence of either change in the poultry isolates, significantly increases pandemic concerns.