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Optimizing environmental safety and cell-killing potential of oncolytic Newcastle Disease virus with modifications of the V, F and HN genes.
- Source :
-
PloS one [PLoS One] 2022 Feb 09; Vol. 17 (2), pp. e0263707. Date of Electronic Publication: 2022 Feb 09 (Print Publication: 2022). - Publication Year :
- 2022
-
Abstract
- Newcastle Disease Virus (NDV) is an avian RNA virus, which was shown to be effective and safe for use in oncolytic viral therapy for several tumour malignancies. The presence of a multi basic cleavage site (MBCS) in the fusion protein improved its oncolytic efficacy in vitro and in vivo. However, NDV with a MBCS can be virulent in poultry. We aimed to develop an NDV with a MBCS but with reduced virulence for poultry while remaining effective in killing human tumour cells. To this end, the open reading frame of the V protein, an avian specific type I interferon antagonist, was disrupted by introducing multiple mutations. NDV with a mutated V gene was attenuated in avian cells and chicken and duck eggs. Although this virus still killed tumour cells, the efficacy was reduced compared to the virulent NDV. Introduction of various mutations in the fusion (F) and hemagglutinin-neuraminidase (HN) genes slightly improved this efficacy. Taken together, these data demonstrated that NDV with a MBCS but with abrogation of the V protein ORF and mutations in the F and HN genes can be safe for evaluation in oncolytic viral therapy.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- A549 Cells
Animals
Apoptosis genetics
Calibration
Capsid Proteins genetics
Cells, Cultured
Chick Embryo
Chlorocebus aethiops
Ducks embryology
HN Protein genetics
Humans
Mutagenesis, Site-Directed methods
Neoplasms pathology
Newcastle disease virus pathogenicity
Newcastle disease virus physiology
Open Reading Frames genetics
Patient Safety
Tumor Microenvironment genetics
Vero Cells
Viral Fusion Proteins adverse effects
Viral Fusion Proteins genetics
Virulence genetics
Virus Replication genetics
Neoplasms therapy
Newcastle disease virus genetics
Oncolytic Virotherapy adverse effects
Oncolytic Virotherapy methods
Oncolytic Virotherapy standards
Oncolytic Viruses genetics
Oncolytic Viruses pathogenicity
Oncolytic Viruses physiology
Viral Structural Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 17
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 35139115
- Full Text :
- https://doi.org/10.1371/journal.pone.0263707