Abstract
Replicating oncolytic viruses provide promising treatment strategies against cancer. However, the success of these viral therapies depends mainly on the complex interactions between the virus particles and the host immune cells. Among these immune cells, macrophages represent one of the first line of defence against viral infections. In this paper, we consider a mathematical model that describes the interactions between a commonly-used oncolytic virus, the Vesicular Stomatitis Virus (VSV), and two extreme types of macrophages: the pro-inflammatory M1 cells (which seem to resist infection with VSV) and the anti-inflammatory M2 cells (which can be infected with VSV). We first show the existence of bounded solutions for this differential equations model. Then we investigate the long-term behaviour of the model by focusing on steady states and limit cycles, and study changes in this long-term dynamics as we vary different model parameters. Moreover, through sensitivity analysis we show that the parameters that have the highest impact on the level of virus particles in the system are the viral burst size (from infected macrophages), the virus infection rate, the M1$\to$M2 polarisation rate, and the M1-induced anti-viral immunity.
Highlights
Viral infections are a major health concern to humans and animals, some viruses have been used for therapeutic purposes [36]
We consider a mathematical model that describes the interactions between a commonly-used oncolytic virus, the Vesicular Stomatitis Virus (VSV), and two extreme types of macrophages: the pro-inflammatory M1 cells and the anti-inflammatory M2 cells
We have considered a mathematical modelling and computational approach to investigate the interaction between an oncolytic virus (Vesicular Stomatitis Virus – VSV) and the innate immunity generated by M1 and M2 macrophages in response to this virus
Summary
Viral infections are a major health concern to humans and animals, some viruses have been used for therapeutic purposes [36]. An important area where viruses are currently being used to alter the course of the disease is cancer research. In this context, non-replicating viruses have been used as cancer vaccines (by engineering them to express tumour antigens that would trigger an anti-tumour immune response) [33], while replicating viruses have been used either as vaccines that can boost the immune response or as oncolytic agents [51]. Viruses can be naturally oncolytic or can be engineered to display oncolytic activity by genetically modifying them to replicate inside cancer cells and lysing them [49]. The efficacy of these viruses is reduced by the presence of anti-viral immune responses. Some of the most important innate immune cells involved in viral clearance are the macrophages
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