Transcriptomic Characterization of the Novel Avian-Origin Influenza A (H7N9) Virus: Specific Host Response and Responses Intermediate between Avian (H5N1 and H7N7) and Human (H3N2) Viruses and Implications for Treatment Options

Josset, Laurence; Zeng, Hui; Kelly, Sara M.; Tumpey, Terrence M.; Katze, Michael G.

human adaptation, including PB2 E627K and hemagglutinin (HA) Q226L (11, 13) . The consequence of these mutations for the host response has not been assessed. Previous studies of H7N9 virus-host interaction have focused on transmissibility and HA binding properties. The H7N9 strain A/Anhui/01/13 (Anhui01) has a mixed ␣2-3/␣2-6 receptor preference, associated with a capacity to efficiently transmit by direct contact but poorly by respiratory droplets in the ferret model (14) . These properties are intermediary between human seasonal influenza viruses that have an ␣2-6 preference and efficiently transmit by respiratory droplets and H5N1 viruses with an ␣2-3 preference that do not transmit efficiently in either respiratory droplet or direct-contact transmission models (14, 15) . Crystallographic structures of HA from H7N9 strains isolated from human patients show that increased avidity for human receptors compared to that of avian H7 virus is due to the Q226L and G186V mutations (16) . Assays of HA binding to human tissue sections revealed an intermediate binding pattern between human IAV (preferentially binding nonciliated cells of apical regions of the trachea) and H5N1 (binding alveolar sections). In addition, a single mutation, G228S, substantially increased HA binding to human receptors in the human respiratory tract (17) .