Abstract

Newcastle disease (ND) is one of the most important diseases of poultry worldwide. In the last decades, molecular research has gained a lot of new information about its causative agent, newcastle disease virus (NDV). In poultry industry, certain strains of NDV have been used for preventive vaccination for more than 60 years. NDV has also been applied to cancer patients with beneficial effects for about 50 years, but this is less well known. The molecular basis for these differential effects of NDV in birds and man have been elucidated in the last decades and are explained in this review. The anti-neoplastic and immune-stimulatory properties in non-permissive hosts such as mouse and man have to do with the strong type I interferon responses induced in these foreign species. Additionally, NDV has the potential to break various types of tumor resistances and also to affect liver fibrosis. A main section is devoted to the benefits of clinical application of NDV and NDV-based vaccines to cancer patients. Reverse genetics technology allowed developing NDV into a vector suitable for gene therapy. Examples will be provided in which genetically engineered NDV is being used successfully as vector against new emerging viruses.

Highlights

  • Studies on the activities of RNA in the cell, in particular about RNA interference against viruses [1,2], have revolutionized our understanding of the many roles played by this macromolecule

  • The virus was capable, during evolution, of adapting to the immune system of birds by generating the frameshift variant protein V that interferes with the type I interferon response of cells from birds

  • Regarding medical application of newcastle disease virus (NDV) in cancer patients, the following immunobiological mechanisms are important: Oncolytic NDV destroys tumor cells and induces a cell death that is immunogenic and initiates a dendritic cells (DCs) towards type 1 (DC1) and T helper cell polarized towards type 1 (Th1) directed anti-tumoral T cell response. This leads to further destruction of tumor cells and to development of tumor-reactive memory T cells

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Summary

Introduction

Studies on the activities of RNA in the cell, in particular about RNA interference against viruses [1,2], have revolutionized our understanding of the many roles played by this macromolecule. This article will deal with the contrasting effects that the avian paramyxovirus newcastle disease virus (NDV) exerts in different species like birds, mice and humans [4]. The recognition of 5 -triphosphate (non-capped) viral leader RNA in the cytoplasm of NDV infected human cells by retinoic-acid-inducible gene I (RIG-I) [5] initiates a strong type I interferon (IFN) response [6] and is a good example of RNA–protein interaction. Another example is a recently identified host cell-derived microRNA which targets RIG-I mRNA for degradation [7]. Diagnostics and Molecular Biology of Newcastle Disease Virus (NDV)

Evolution
History and Classification
Morphology
Molecular Biology
Reverse Genetics
Tumor Selective Replication
Oncolysis and Immunogenic Cell Death
Post-Oncolytic Immune Response
Immunostimulatory Properties
Type I Interferon Response
Studies with Human Cells
Studies with Murine Cells
Immune Escape from Type I Interferon Responses
NDV in Man
NDV in Birds
Ebola in Man
Anti-Tumor Effects in Vivo
Potential to Break Therapy Resistancies
Anti-Fibrotic Activity
Industrial Application
High Safety Profile
Treatment by Oncolytic NDV
Treatment by NDV Oncolysate Vaccines
Tumors and Fibrosis in Mice
Tumors in Man
Treatment by ATV-NDV with Attached Bispecific Antibody
Treatment by Autologous NDV Oncolysate-Pulsed DCs
Future Aspects
Viral HN Gene as Vaccine Adjuvant
Recombinant NDV as a Vaccine Vector
RecNDV as a Vaccine Vector against Emerging Pathogens
Harnessing Oncolytic Virus-Mediated Anti-Tumor Immunity
Using NDV as Vector against New Emerging Virus Diseases
Findings
Conclusions

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