Newcastle disease virus induces pro-inflammatory conditions and type I interferon for counter-acting Treg activity

Int J Oncol. 2012 Mar;40(3):840-50. doi: 10.3892/ijo.2011.1265. Epub 2011 Nov 16.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Bronchoalveolar Lavage Fluid / virology
  • Cell Survival / genetics
  • Cell Survival / immunology
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / immunology
  • DEAD-box RNA Helicases / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology*
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / virology*
  • Interferon Regulatory Factor-3 / immunology
  • Interferon Regulatory Factor-3 / metabolism
  • Interferon Regulatory Factor-7 / immunology
  • Interferon-alpha / immunology*
  • Interferon-alpha / metabolism
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Newcastle disease virus / genetics
  • Newcastle disease virus / immunology*
  • Newcastle disease virus / metabolism
  • Oncolytic Virotherapy / methods
  • Oncolytic Viruses / genetics
  • Oncolytic Viruses / immunology*
  • Oncolytic Viruses / metabolism
  • Receptor, Interferon alpha-beta / immunology
  • Receptor, Interferon alpha-beta / metabolism
  • Receptors, Immunologic
  • T-Lymphocytes, Regulatory / immunology*
  • Virus Replication / immunology

Substances

  • IFNAR1 protein, human
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • Interferon-alpha
  • Receptors, Immunologic
  • Receptor, Interferon alpha-beta
  • Interleukin-12
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases