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.

Polarized human bronchial epithelial cells (Calu-3) possess multiple features of in vivo airway epithelium and have been used previously as an in vitro model for multiple studies of influenza virus-host interaction (19) (20) (21) or for studying other respiratory viruses (22, 23) . Here, polarized confluent monolayers of Calu-3 cells were infected apically with the avian-origin IAVs A/Anhui/01/2013 (H7N9) (An-hui01), A/Netherland/219/2003 (H7N7) (NL219), A/Vietnam/ 1203/2004 (H5N1) (VN1203), or a human seasonal virus, A/Panama/2007/1999 (H3N2) (Pan99) at a multiplicity of infec-tion (MOI) of 1. Viral replication was assessed at 3, 7, 12, and 24 h postinoculation [hpi] by standard plaque assays. As shown in Fig. 1 , H7N9 replicated to levels similar to those of H5N1 at 3 hpi, and to those of other IAVs at 12 hpi. Titers of H7N9 were slightly lower than those of other IAVs at 7 hpi but reached a slightly higher peak at 24 hpi, with an average number of PFU/ml of 8.3 (Ϯ0.04) for H7N9 and 7 (Ϯ0.3) for other IAVs. Cytopathic effects and destruction of the cell monolayer were observed at 24 hpi for human H3N2 and avian H7N7 IAVs and to a more limited extent after infection by H7N9 and H5N1 IAVs.