Institute of Mathematics and Informatics, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria.
University of Medicine and Pharmacy "Grigore T. Popa", Universitatii 16, Iaşi, Romania.
Bull Math Biol. 2019 Dec;81(12):4951-4976. doi: 10.1007/s11538-019-00664-3. Epub 2019 Sep 20.
Immature dengue virions contained in patient blood samples are essentially not infectious because the uncleaved surface protein prM renders them incompetent for membrane fusion. However, the immature virions regain full infectivity when they interact with anti-prM antibodies, and once opsonised virion fusion into Fc receptor-expressing cells is facilitated. We propose a within-host mathematical model for the immune response which takes into account the dichotomy between mature infectious and immature noninfectious dengue virions. The model accounts for experimental observations on the different interactions of plasmacytoid dendritic cells with infected cells producing virions with different infectivity. We compute the basic reproduction number as a function of the proportion of infected cells producing noninfectious virions and use numerical simulations to compare the host's immune response in a primary and a secondary dengue infections. The results can be placed in the immunoregulatory framework with plasmacytoid dendritic cells serving as a bridge between the innate and adaptive immune response, and pose questions for potential experimental work to validate hypothesis about the evolutionary context whereby the virus strives to maximise its chance for transmission from the human host to the mosquito vector.
患者血液样本中包含的未成熟登革热病毒粒子基本上没有传染性，因为未切割的表面蛋白 prM 使它们无法进行膜融合。然而，当未成熟的病毒粒子与抗 prM 抗体相互作用时，它们会恢复完全的感染力，并且一旦被调理的病毒粒子融合到表达 Fc 受体的细胞中，就会得到促进。我们提出了一个宿主内免疫反应的数学模型，该模型考虑到成熟感染性和不成熟非感染性登革热病毒粒子之间的二分法。该模型解释了实验观察到的浆细胞样树突状细胞与产生不同感染力的病毒粒子的感染细胞的不同相互作用。我们将基本繁殖数计算为产生非感染性病毒粒子的感染细胞比例的函数，并使用数值模拟比较原发性和继发性登革热感染中宿主的免疫反应。这些结果可以放在浆细胞样树突状细胞作为先天和适应性免疫反应之间桥梁的免疫调节框架中，并提出了一些问题，供潜在的实验工作验证关于病毒在进化背景下努力最大限度地提高从人类宿主传播到蚊子媒介的机会的假设。
