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Significance Deep-sequencing of viral genomes based on original specimens from H7N9-infected patients and the surrounding poultry/environment has provided the first in-depth data on virus adaptation at the interface between poultry and humans. In contrast to the consistent dominance of 627E in poultry-derived H7N9, diverse but longitudinally changing ratios of the mammalian signature substitution PB2-E627K from patient specimens indicate a dynamic viral adaptation during infection, termed “genetic tuning” of avian influenza viruses in new hosts. Furthermore, the correlation between rapid host adaptation of H7N9 PB2-627 and the disease severity in patients is brought to light. Of note, under a one-health vision, our study provides direct big data evidence that “genetic tuning” of PB2-E627K is associated with H7N9 pathogenicity during human infection.

Dynamic PB2-E627K substitution of influenza H7N9 virus indicates the in vivo genetic tuning and rapid host adaptation