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.

Although the H7N9 outbreak has entered a stationary state in China, with only a few cases reported since late May 2013, there are concerns that H7N9 may reappear in the winter. Other avian IAVs, such as H5N1, indeed have a seasonal pattern, with an increase in human infection during the winter. In addition, H7N9 is likely still circulating in poultry. Several studies have shown that H7N9 possess genetic markers associated with adaptation to humans, allowing higher replication in mammal cells (PB2 E627K) and increased binding of ␣2-6 human receptors (HA Q226L and G186V). Further adaptation of H7N9 to humans is of concern, since it could lead to efficient human-to-human transmission. In this study, we have shown that cell responses to H7N9 infection are more similar to those to H3N2 infection than to those to infection with avian H5N1 or H7N7 viruses, which implies that H7N9 has adapted to the human host. Some of the human IAVlike transcriptomic responses of H7N9 were related to similar lower induction of several genes involved in the eicosanoid pathway. Some lipid mediators from these pathways were recently identified as correlates of the pathogenic or resolution phase of IAV infection in mice (26) and had antiviral effect in cells and mice (27) . Our analysis revealed that the eicosanoid pathway is differentially regulated by avian and human IAVs, with a potential impact on lung inflammation and viral replication. Importantly, differences in the transcriptomic response to infection were not related to major differences in replication between viruses. We previously observed higher replication of the Anhui01 H7N9 strain than of the seasonal A/Texas/50/2012 (H3N2) virus in Calu-3 cells (14) . However, at this higher MOI and using the more replicative A/Panama/2004/99 (H3N2), similar replication between avian and human IAVs was observed.