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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bronchoalveolar Lavage Fluid / immunology
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Bronchoalveolar Lavage Fluid / virology
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Cell Survival / genetics
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Cell Survival / immunology
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DEAD Box Protein 58
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DEAD-box RNA Helicases / immunology
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DEAD-box RNA Helicases / metabolism
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Dendritic Cells / virology*
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Epithelial Cells / immunology
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Epithelial Cells / metabolism
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Epithelial Cells / virology
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Gene Expression Regulation, Neoplastic / immunology
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Humans
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Inflammation / genetics
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Inflammation / immunology
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Inflammation / metabolism
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Inflammation / virology*
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Interferon Regulatory Factor-3 / immunology
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Interferon Regulatory Factor-3 / metabolism
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Interferon Regulatory Factor-7 / immunology
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Interferon-alpha / immunology*
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Interferon-alpha / metabolism
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Interleukin-12 / immunology
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Interleukin-12 / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Newcastle disease virus / genetics
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Newcastle disease virus / immunology*
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Newcastle disease virus / metabolism
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Oncolytic Virotherapy / methods
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Oncolytic Viruses / genetics
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Oncolytic Viruses / immunology*
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Oncolytic Viruses / metabolism
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Receptor, Interferon alpha-beta / immunology
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Receptor, Interferon alpha-beta / metabolism
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Receptors, Immunologic
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T-Lymphocytes, Regulatory / immunology*
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Virus Replication / immunology
Substances
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IFNAR1 protein, human
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Interferon Regulatory Factor-3
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Interferon Regulatory Factor-7
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Interferon-alpha
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Receptors, Immunologic
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Receptor, Interferon alpha-beta
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Interleukin-12
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RIGI protein, human
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DEAD Box Protein 58
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DEAD-box RNA Helicases