论文标题

病毒入口后细胞感染的随机衰竭:对感染结果和抗病毒治疗的影响

Stochastic failure of cell infection post viral entry: Implications for infection outcomes and antiviral therapy

论文作者

Quirouette, Christian, Cresta, Daniel, Li, Jizhou, Wilkie, Kathleen P., Liang, Haozhao, Beauchemin, Catherine A. A.

论文摘要

病毒感染可以用很少甚至单一的感染性病毒体开始,因此可能灭绝,即随机无法大量占据或散布。成功进入细胞的完全有能力的感染性病毒素有很多方法可以引起生产性感染,即一种产生传染性病毒后代的感染。尽管已经开发了许多离散的随机数学模型(DSM),并用于估计病毒感染的灭绝概率,但病毒进入后通常会忽略感染失败。本文介绍的DSM引入了参数$γ\ in(0,1] $,这与Virion进入细胞的可能性相对应,这将导致细胞感染。我们得出了一种新的DSM感染可能性的表达,并发现概率的概率是$γ$的概率,并发现概率的范围是$γ$的最大程度的表达。我们使用DSM的病毒或病毒进入细胞的抗病患者,研究了所谓的灭绝与已建立的病毒感染所消耗的细胞的差异,并发现这种区别在生物学上毫无意义,因为在灭绝方法上,我们的感染范围是一种释放的。寿命,尽管先前提出了这种效果的要求[Pearson 2011,doi:10.1371/journal.pcbi.1001058]。关键的抗病毒功效。

A virus infection can be initiated with very few or even a single infectious virion, and as such can become extinct, i.e. stochastically fail to take hold or spread significantly. There are many ways that a fully competent infectious virion, having successfully entered a cell, can fail to cause a productive infection, i.e. one that yields infectious virus progeny. Though many discrete, stochastic mathematical models (DSMs) have been developed and used to estimate a virus infection's extinction probability, these typically neglect infection failure post viral entry. The DSM presented herein introduces parameter $γ\in(0,1]$ which corresponds to the probability that a virion's entry into a cell will result in a productive cell infection. We derive an expression for the likelihood of infection extinction in this new DSM, and find that prophylactic therapy with an antiviral acting to reduce $γ$ is best at increasing an infection's extinction probability, compared to antivirals acting on the rates of virus production or virus entry into cells. Using the DSM, we investigate the difference in the fraction of cells consumed by so-called extinct versus established virus infections, and find that this distinction becomes biologically meaningless as the probability of extinction approaches 100%. We show that infections wherein virus is release by an infected cell as a single burst, rather than at a constant rate over the cell's infectious lifespan, has the same probability of infection extinction, despite previous claims to this effect [Pearson 2011, doi:10.1371/journal.pcbi.1001058]. Instead, extending previous work by others [Yan 2016, doi:10.1007/s00285-015-0961-5], we show how the assumed distribution for the stochastic virus burst size, affects the extinction probability and associated critical antiviral efficacy.

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