Using Mathematical Modelling to Explore Hypotheses about the Role of Bovine Epithelium Structure in Foot-And-Mouth Disease Virus-Induced Cell Lysis

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. FMD virus (FMDV) shows a strong tropism for epithelial cells, and FMD is characterised by cell lysis and the development of vesicular lesions in certain epithelial tissues (for example, the tongue). By contrast, other epithelial tissues do not develop lesions, despite being sites of viral replication (for example, the dorsal soft palate). The reasons for this difference are poorly understood, but hypotheses are difficult to test experimentally. In order to identify the factors which drive cell lysis, and consequently determine the development of lesions, we developed a partial differential equation model of FMDV infection in bovine epithelial tissues and used it to explore a range of hypotheses about epithelium structure which could be driving differences in lytic behaviour observed in different tissues. Our results demonstrate that, based on current parameter estimates, epithelial tissue thickness and cell layer structure are unlikely to be determinants of FMDV-induced cell lysis. However, differences in receptor distribution or viral replication amongst cell layers could influence the development of lesions, but only if viral replication rates are much lower than current estimates.

口蹄疫（Foot-and-mouth disease, FMD）是一种极具传染性的偶蹄动物传染病。口蹄疫病毒（Foot-and-mouth disease virus, FMDV）对上皮细胞具有极强的嗜性；口蹄疫的典型特征为细胞裂解，以及部分上皮组织（如舌部）出现水疱性病变。与之相对的是，尽管部分上皮组织（如软腭背侧）存在病毒复制，却不会产生病变。这种差异背后的机制目前尚不明确，且相关假说难以通过实验验证。为明确驱动细胞裂解的相关因素，进而确定病变的发生机制，本研究构建了牛上皮组织口蹄疫病毒感染的偏微分方程（partial differential equation）模型，并利用该模型对一系列可能导致不同组织间裂解行为差异的上皮结构假说展开探究。研究结果显示，基于当前的参数估计值，上皮组织厚度与细胞层结构并非口蹄疫病毒诱导细胞裂解的决定性因素。不过，若病毒复制速率远低于当前估计值，则细胞层间受体分布或病毒复制的差异可能会影响病变的发生发展。