title: Newcastle disease virus induces pro-inflammatory conditions and type             I interferon for counter-acting Treg activity.
abstract: Newcastle disease virus (NDV) is a negative sense RNA paramyxovirus of birds which in human tumor cells, in contrast to human non-tumor cells, has shown replication competence leading to tumor cell death (i.e., tumor selectivity and viral oncolysis). Our study demonstrates that this virus induces high levels of pro-inflammatory cytokines in the bronchial lavage fluid of mice after nasal application and also in vitro in human dendritic cells (DCs). NDV is known as a very efficient inductor of type I interferon (IFN). The presented data show the key role played by the cell surface receptor to type I IFN (IFNAR) but not by the interferon transcription factors IRF-3 and IRF-7 in the induction of the important pro-inflammatory cytokine IL-12 upon transcription of NDV genes in DCs. We show that NDV activates in infected cells the helicase RIG-I. In Tregs, the activation of RIG-I was shown in other studies to inhibit the suppressive function of these cells. We thus conclude that NDV in tumor therapy may help to stimulate T effector cells but also to block Treg cells, thereby alleviating a brake to antitumor activity.
authors.affiliation: German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, Germany.
authors.forename: Philippe
authors.initials: P
authors.lastname: Fournier
authors.forename: Annette
authors.initials: A
authors.lastname: Arnold
authors.forename: Holger
authors.initials: H
authors.lastname: Wilden
authors.forename: Volker
authors.initials: V
authors.lastname: Schirrmacher
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000821:virology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D050838:Interferon Regulatory Factor-3 / Q000276:immunology / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009522:Newcastle disease virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
chemical_list: C507964:IFNAR1 protein, human; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; D011971:Receptors, Immunologic; D053633:Receptor, Interferon alpha-beta; D018664:Interleukin-12; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases