title: Transcription Factor Runx3 Is Induced by Influenza A Virus and Double-Strand RNA and Mediates Airway Epithelial Cell Apoptosis.
abstract: Influenza A virus (IAV) targets airway epithelial cells and exploits the host cell machinery to replicate, causing respiratory illness in annual epidemics and pandemics of variable severity. The high rate of antigenic drift (viral mutation) and the putative antigenic shift (reassortant strains) have raised the need to find the host cell inducible factors modulating IAV replication and its pathogenesis to develop more effective antiviral treatment. In this study, we found for the first time that transcription factor Runx3, a developmental regulator and tumor suppressor, was induced by IAV H1N1 and H3N2, viral RNA, a synthetic analog of viral double-stranded RNA (dsRNA) polyinosinic-polycytidylic acid, and type-II interferon-γ (IFNγ) in human airway epithelial cells. Whereas Runx3 was essentially not induced by type-I IFNα and type-III IFNλ, we show that Runx3 induction by IAV infection and viral RNA is mediated through the innate immune receptor MDA5 and the IκB kinase-β-NF-κB pathway. Moreover, we provide substantial evidence indicating that Runx3 plays a crucial role in airway epithelial cell apoptosis induced by IAV infection and dsRNA through the activation of extrinsic and intrinsic apoptosis pathways. Thus, we have identified Runx3 as an inducible and important transcription factor modulating IAV-induced host epithelial cell apoptosis.
authors.affiliation: Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.
authors.forename: Huachen
authors.initials: H
authors.lastname: Gan
authors.affiliation: Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Hao
authors.affiliation: Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.|Texas Lung Injury Institute, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Idell
authors.affiliation: Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D000072640:Interferon-Induced Helicase, IFIH1; D016328:NF-kappa B / Q000378:metabolism; D011070:Poly I-C / Q000276:immunology / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000276:immunology / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000378:metabolism
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C