title: Importance of retinoic acid-inducible gene I and of receptor for type             I interferon for cellular resistance to infection by Newcastle disease virus.
abstract: Newcastle disease virus (NDV) is an avian paramyxovirus with oncolytic properties             which shows promising effects in the treatment of cancer. Anti-cancer effects             are due to the virus ability: i) to replicate in and kill tumor cells, leading             finally to their selective elimination; and ii) to induce the stimulation of antitumor             activities in immune cells. NDV does not harm normal cells and has a high safety             profile. In this study, we first report a direct correlation between the degree             of cell resistance to NDV infection and the cellular expression of the retinoic             acid-inducible gene I (RIG-I) which is a cytosolic viral RNA receptor. RIG-I plays             an important role in the recognition of and response to infection by RNA viruses.             We also demonstrate that impairment of the interferon (IFN) pathway through deletion             of the receptor for type I IFN (IFNR1) in primary macrophages leads to NDV replication.             In tumor cells, addition of exogenous IFN-α4 is shown to lead to tumor growth             reduction and inhibition of viral replication. Finally, increase of the RIG-I             concentration of tumor cells via plasmid transfection is shown to be associated             with a stronger resistance to NDV infection. These findings shed new light on             the crucial role played by the cytosolic receptor RIG-I and the plasma membrane             receptor IFNR1 as key molecules to protect cells against infection by NDV.
authors.affiliation: German Cancer Research Center, Im Neuenheimer Feld 280, D-69120                     Heidelberg, Germany.
authors.forename: Philippe
authors.initials: P
authors.lastname: Fournier
authors.forename: Holger
authors.initials: H
authors.lastname: Wilden
authors.forename: Volker
authors.initials: V
authors.lastname: Schirrmacher
mesh_terms: D000818:Animals; D001717:Birds; D045744:Cell Line, Tumor; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D060467:Disease Resistance; D006801:Humans; D007372:Interferons / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009521:Newcastle Disease / Q000276:immunology* / Q000821:virology; D009522:Newcastle disease virus / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D050130:Oncolytic Virotherapy / Q000379:methods; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic; D015398:Signal Transduction; D014162:Transfection; D014779:Virus Replication
chemical_list: C508032:Ifnar1 protein, mouse; D011971:Receptors, Immunologic; D053633:Receptor, Interferon alpha-beta; D007372:Interferons; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases