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Velogenic newcastle disease virus as an oncolytic virotherapeutics: in vitro characterization
Rajiv Kumar1, Ashok K Tiwari, Uttara Chaturvedi
1Molecular Biology Laboratory, Department of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar 243122, UP, India.
Abstract:
Cancer is one of the killer diseases in humans and needs alternate curative measures despite recent improvement in modern treatment modalities. Oncolytic virotherapy seems to be a promising nonconventional way to treat cancers. Newcastle disease virus (NDV), a poultry virus, is nonpathogenic to human and domestic animals and has a long history of being used in oncotherapy research in several preclinical studies. The ability of NDV to successfully infect and destroy cancer cells is dependent on the strain and the pathotype of the virus. Adaptation of viruses to heterologous hosts without losing its replicative and oncolytic potential is prerequisite for use as cancer virotherapeutics. In the present study, velogenic NDV was adapted for replication in HeLa cells, and its cytotoxic potential was evaluated by observing morphological, biochemical, and nuclear landmarks of apoptosis. Our results indicated that the NDV-induced apoptosis in HeLa cells was dependent on upregulation of TNF-related apoptosis-inducing ligand (TRAIL) and caspases activation. Different determinants of apoptosis evaluated in the present study indicated that this strain could be a promising candidate for cancer therapy in future.
Insights
Newcastle disease virus (NDV) effectively triggered cancer cell death by inducing apoptosis. This adaptation of NDV in HeLa cells shows promise for future cancer virotherapy treatments.
Area of Science:
- Oncology
- Virology
- Cell Biology
Background:
- Cancer remains a leading cause of death, necessitating novel therapeutic strategies beyond conventional treatments.
- Oncolytic virotherapy, using viruses to target and destroy cancer cells, presents a promising alternative approach.
- Newcastle disease virus (NDV), a poultry virus safe for humans, has demonstrated potential in preclinical cancer therapy studies.
Purpose of the Study:
- To adapt a velogenic strain of Newcastle disease virus (NDV) for replication in human cancer cells (HeLa).
- To evaluate the cytotoxic potential and apoptosis-inducing mechanisms of the adapted NDV in HeLa cells.
Main Methods:
- Adaptation of velogenic NDV for replication in HeLa cells.
- Assessment of NDV-induced cell death through morphological, biochemical, and nuclear analysis of apoptosis.
- Investigation of apoptosis-related pathways, including TNF-related apoptosis-inducing ligand (TRAIL) and caspases.
Main Results:
- The adapted velogenic NDV replicated effectively in HeLa cells.
- NDV infection induced significant apoptosis in HeLa cells, evidenced by characteristic cellular changes.
- Apoptosis was mediated by the upregulation of TRAIL and activation of caspases.
Conclusions:
- The adapted velogenic NDV strain demonstrates potent oncolytic activity against HeLa cancer cells.
- NDV-induced apoptosis involves TRAIL upregulation and caspase activation, key pathways in programmed cell death.
- This adapted NDV strain holds promise as a candidate for future cancer virotherapy applications.
