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

摘要: ABSTRACT A novel avian-origin H7N9 influenza virus (IAV) emerged in China 2013, causing mild to lethal human respiratory infections. originated with multiple reassortment events between avian viruses and carries genetic markers of adaptation. Determining whether induces a host response closer that or IAV is important order better characterize this emerging virus. Here we compared the lung epithelial cell infection A/Anhui/01/13 (H7N9) highly pathogenic H5N1, H7N7, seasonal H3N2 IAV. The transcriptomic was specific strain but more similar than other IAVs. both elicited responses related eicosanoid signaling chromatin modification, whereas specifically induced genes regulating cycle transcription. Among IAVs, closest by H5N1 Host common included lack induction antigen presentation pathway reduced proinflammatory cytokine H3N2. Repression these could have an impact on immunogenicity virulence humans. Finally, using genome-based drug repurposing approach, identified several drugs predicted regulate may act as potential antivirals, including kinase inhibitors, well FDA-approved drugs, such troglitazone minocycline. Importantly, validated minocycline inhibited replication vitro , suggesting our computational approach holds promise for identifying antivirals. IMPORTANCE Whether will be next pandemic persist sporadically infect humans from its reservoir, not known yet. High-throughput profiling allows rapid characterization virus-host interactions generates many hypotheses accelerate understanding responsiveness threat. We show cellular reflecting new adaptation dissecting guide host-directed antiviral development.