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具有固定细胞内时滞和联合药物治疗的扩散病毒模型。

A diffusive virus model with a fixed intracellular delay and combined drug treatments.

机构信息

Department of Natural Science in the Center for General Education, Chang Gung University, Guishan, Taoyuan, 333, Taiwan.

Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung Branch, Keelung, 204, Taiwan.

出版信息

J Math Biol. 2021 Jul 29;83(2):19. doi: 10.1007/s00285-021-01646-7.

Abstract

The method of administration of an effective drug treatment to eradicate viruses within a host is an important issue in studying viral dynamics. Overuse of a drug can lead to deleterious side effects, and overestimating the efficacy of a drug can result in failure to treat infection. In this study, we proposed a reaction-diffusion within-host virus model which incorporated information regarding spatial heterogeneity, drug treatment, and the intracellular delay to produce productively infected cells and viruses. We also calculated the basic reproduction number [Formula: see text] under the assumptions of spatial heterogeneity. We have shown that the infection-free periodic solution is globally asymptotically stable when [Formula: see text], whereas when [Formula: see text] there is an infected periodic solution and the infection is uniformly persistent. By conducting numerical simulations, we also revealed the effects of various parameters on the value of [Formula: see text]. First, we showed that the dependence of [Formula: see text] on the intracellular delay could be monotone or non-monotone, depending on the death rate of infected cells in the immature stage. Second, we found that the mobility of infected cells or virions could facilitate the virus clearance. Third, we found that the spatial fragmentation of the virus environment enhanced viral infection. Finally, we showed that the combination of spatial heterogeneity and different sets of diffusion rates resulted in complicated viral dynamic outcomes.

摘要

将有效的药物治疗方法施用于宿主以消灭病毒是研究病毒动力学的一个重要问题。过度使用药物会导致有害的副作用,而高估药物的疗效则可能导致治疗感染失败。在这项研究中,我们提出了一个包含空间异质性、药物治疗和产生有生产力感染细胞和病毒的细胞内延迟信息的宿主内病毒反应-扩散模型。我们还计算了在空间异质性假设下基本繁殖数 [Formula: see text]。我们已经表明,当 [Formula: see text] 时,无感染的周期解是全局渐近稳定的,而当 [Formula: see text] 时,存在感染的周期解,并且感染是一致持久的。通过进行数值模拟,我们还揭示了各种参数对 [Formula: see text] 值的影响。首先,我们表明,[Formula: see text] 对细胞内延迟的依赖性可能是单调的或非单调的,这取决于不成熟阶段感染细胞的死亡率。其次,我们发现感染细胞或病毒粒子的迁移能力可以促进病毒清除。第三,我们发现病毒环境的空间碎片化增强了病毒感染。最后,我们表明,空间异质性和不同扩散率集的组合导致了复杂的病毒动力学结果。

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