Optimization of SOX2 Expression for Enhanced Glioblastoma Stem Cell Virotherapy

The Zika virus has been shown to infect glioblastoma stem cells via the membrane receptor <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow><mml:msub><mml:mi>α</mml:mi> <mml:mi>v</mml:mi></mml:msub> <mml:msub><mml:mi>β</mml:mi> <mml:mn>5</mml:mn></mml:msub> </mml:mrow> </mml:math> , which is activated by the stem-specific transcription factor SOX2. Since the expression level of SOX2 is an important predictive marker for successful virotherapy, it is important to understand the fundamental mechanisms of the role of SOX2 in the dynamics of cancer stem cells and Zika viruses. In this paper, we develop a mathematical ODE model to investigate the effects of SOX2 expression levels on Zika virotherapy against glioblastoma stem cells. Our study aimed to identify the conditions under which SOX2 expression level, viral infection, and replication can reduce or eradicate the glioblastoma stem cells. Analytic work on the existence and stability conditions of equilibrium points with respect to the basic reproduction number are provided. Numerical results were in good agreement with analytic solutions. Our results show that critical threshold levels of both SOX2 and viral replication, which change the stability of equilibrium points through population dynamics such as transcritical and Hopf bifurcations, were observed. These critical thresholds provide the optimal conditions for SOX2 expression levels and viral bursting sizes to enhance therapeutic efficacy of Zika virotherapy against glioblastoma stem cells. This study provides critical insights into optimizing Zika virus-based treatment for glioblastoma by highlighting the essential role of SOX2 in viral infection and replication.