Kim Dongwook, Puig Abraham, Rabiei Faranak, Hawkins Erial J, Hernandez Talia F, Sung Chang K
Department of Mathematics, College of Arts and Sciences, Texas A&M University-Kingsville, Kingsville, TX 78363, USA.
Department of Biological and Health Sciences, College of Arts and Sciences, Texas A&M University-Kingsville, Kingsville, TX 78363, USA.
Symmetry (Basel). 2024 Sep;16(9). doi: 10.3390/sym16091186. Epub 2024 Sep 10.
The Zika virus has been shown to infect glioblastoma stem cells via the membrane receptor , 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.
寨卡病毒已被证明可通过膜受体感染胶质母细胞瘤干细胞，该膜受体由干细胞特异性转录因子SOX2激活。由于SOX2的表达水平是病毒疗法成功的重要预测标志物，因此了解SOX2在癌症干细胞和寨卡病毒动态中的作用的基本机制非常重要。在本文中，我们建立了一个数学常微分方程模型来研究SOX2表达水平对寨卡病毒治疗胶质母细胞瘤干细胞的影响。我们的研究旨在确定SOX2表达水平、病毒感染和复制能够减少或根除胶质母细胞瘤干细胞的条件。提供了关于平衡点相对于基本再生数的存在性和稳定性条件的分析工作。数值结果与解析解吻合良好。我们的结果表明，观察到了SOX2和病毒复制的临界阈值水平，它们通过跨临界和霍普夫分岔等种群动态改变平衡点的稳定性。这些临界阈值为SOX2表达水平和病毒爆发大小提供了最佳条件，以提高寨卡病毒疗法对胶质母细胞瘤干细胞的治疗效果。本研究通过强调SOX2在病毒感染和复制中的重要作用，为优化基于寨卡病毒的胶质母细胞瘤治疗提供了关键见解。
