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Published on: May 2, 2011
SARS-CoV-2 RBD protein enhances the oncolytic activity of the vesicular stomatitis virus
Almohanad A Alkayyal1,2, Reham Ajina2,3, Marco Cacciabue4,5
1Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia.
Abstract:
Despite recent advances in the research on oncolytic viruses (OVs), a better understanding of how to enhance their replication is key to improving their therapeutic index. Understanding viral replication is important to improve treatment outcomes based on enhanced viral spreading within the tumor milieu. The VSV-Δ51 oncolytic virus has been widely used as an anticancer agent with a high selectivity profile. In this study, we examined the role of the SARS-CoV-2 spike protein receptor-binding domain (RBD) in enhancing VSV-Δ51 viral production and oncolytic activity. To test this hypothesis, we first generated a novel VSV-Δ51 mutant that encoded the SARS-COV-2 RBD and compared viral spreading and viral yield between VSV-Δ51-RBD and VSV-Δ51 in vitro. Using the viral plaque assay, we demonstrated that the presence of the SARS-CoV-2 RBD in the VSV-Δ51 genome is associated with a significantly larger viral plaque surface area and significantly higher virus titers. Subsequently, using an ATP release-based assay, we demonstrated that the SARS-CoV-2 RBD could enhance VSV-Δ51 oncolytic activity in vitro. This observation was further supported using the B16F10 tumor model. These findings highlighted a novel use of the SARS-CoV-2 RBD as an anticancer agent.
Insights
Researchers enhanced oncolytic virus (OV) therapy by incorporating the SARS-CoV-2 spike protein receptor-binding domain (RBD) into VSV-Δ51. This modification significantly improved viral replication and oncolytic activity against tumors.
Area of Science:
- Virology
- Oncology
- Molecular Biology
Background:
- Oncolytic viruses (OVs) show promise in cancer therapy, but enhancing their replication and therapeutic index is crucial.
- Vesicular stomatitis virus, strain Indiana, lacking the matrix protein (VSV-Δ51) is a selective oncolytic virus used in cancer research.
- Improving viral spreading within the tumor microenvironment is key to effective OV therapy.
Purpose of the Study:
- To investigate the role of the SARS-CoV-2 spike protein receptor-binding domain (RBD) in enhancing VSV-Δ51 viral production.
- To evaluate the impact of SARS-CoV-2 RBD incorporation on the oncolytic activity of VSV-Δ51.
- To determine if SARS-CoV-2 RBD can serve as a novel anticancer agent.
Main Methods:
- Generation of a VSV-Δ51 mutant encoding the SARS-CoV-2 RBD (VSV-Δ51-RBD).
- In vitro comparison of viral spreading and yield between VSV-Δ51-RBD and VSV-Δ51 using viral plaque assays.
- Assessment of in vitro oncolytic activity using an ATP release-based assay.
- In vivo evaluation in a B16F10 tumor model.
Main Results:
- VSV-Δ51-RBD exhibited significantly larger viral plaque surface area and higher virus titers compared to VSV-Δ51 in vitro.
- The SARS-CoV-2 RBD significantly enhanced the oncolytic activity of VSV-Δ51 in vitro.
- Enhanced oncolytic activity was further supported by in vivo studies using the B16F10 tumor model.
Conclusions:
- The SARS-CoV-2 spike protein RBD can enhance VSV-Δ51 viral production and oncolytic efficacy.
- Incorporating the SARS-CoV-2 RBD into VSV-Δ51 represents a novel strategy for improving oncolytic virotherapy.
- The SARS-CoV-2 RBD shows potential as a novel anticancer agent when engineered into oncolytic viruses.
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