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Mathematical modelling of reoviruses in cancer cell cultures
Arwa Abdulla Baabdulla1, Francisca Cristi2,3,4, Maya Shmulevitz2,3,4
1Department of Mathematical Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Abstract:
Oncolytic virotherapy has emerged as a potential cancer therapy, utilizing viruses to selectively target and replicate within cancer cells while preserving normal cells. In this paper, we investigate the oncolytic potential of unmodified reovirus T3wt relative to a mutated variant SV5. In animal cancer cell monolayer experiments it was found that SV5 was more oncolytic relative to T3wt. SV5 forms larger sized plaques on cancer cell monolayers and spreads to farther distances from the initial site of infection as compared to T3wt. Paradoxically, SV5 attaches to cancer cells less efficiently than T3wt, which lead us to hypothesize that there might be an optimal binding affinity with maximal oncolytic activity. To understand the relationship between the binding process and virus spread for T3wt and SV5, we employ mathematical modelling. A reaction-diffusion model is applied, which is fit to the available data and then validated on data that were not used for the fit. Analysis of our model shows that there is an optimal binding rate that leads to maximum viral infection of the cancer monolayer, and we estimate this value for T3wt and SV5. Moreover, we find that the viral burst size is an important parameter for viral spread, and that a combination of efficient binding and large burst sizes is a promising direction to further develop anti-cancer viruses.
Insights
Oncolytic virotherapy uses viruses to fight cancer. Mathematical modeling revealed an optimal binding rate for maximal viral infection and spread, guiding the development of more effective oncolytic viruses.
Area of Science:
- Oncolytic virotherapy
- Cancer biology
- Mathematical modeling of viral dynamics
Background:
- Oncolytic virotherapy utilizes viruses to selectively infect and destroy cancer cells, offering a promising therapeutic strategy.
- Reovirus T3wt and its mutated variant SV5 are investigated for their oncolytic potential.
- SV5 demonstrates enhanced oncolytic activity compared to T3wt in cell culture experiments.
Purpose of the Study:
- To investigate the relationship between viral binding affinity and oncolytic activity.
- To understand the factors influencing viral spread in cancer cell monolayers.
- To determine the optimal binding rate for maximal viral infection and spread.
Main Methods:
- In vitro experiments using animal cancer cell monolayers to assess oncolytic activity and plaque formation.
- Mathematical modeling using a reaction-diffusion model to analyze viral binding and spread dynamics.
- Model fitting and validation using experimental data for reovirus T3wt and SV5.
Main Results:
- SV5 exhibited greater oncolytic potential, forming larger plaques and spreading further than T3wt.
- Despite less efficient attachment, SV5 showed higher oncolysis, suggesting an optimal binding affinity.
- Mathematical modeling identified an optimal binding rate for maximum viral infection and highlighted viral burst size as crucial for spread.
Conclusions:
- There exists an optimal binding affinity for maximizing oncolytic virus efficacy.
- Viral burst size significantly influences viral spread, a key factor in oncolytic virotherapy.
- Combining efficient binding with large burst sizes is a promising strategy for developing improved anti-cancer viruses.
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