The reproduction number and its probability distribution for stochastic viral dynamics.

The reproduction number and its probability distribution for stochastic viral dynamics.
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随机病毒动力学的繁殖数及其概率分布。

DOI:
10.1098/rsif.2023.0400
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发表时间:
2024-01
期刊:
Journal of the Royal Society, Interface
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其他
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我们考虑单个感染细胞的随机模型。繁殖数 R 被理解为一个随机变量,代表易感(目标细胞)群体中一个初始感染细胞感染的新细胞的数量。 R 的变异部分是由于病毒爆发大小(受感染细胞在其一生中产生的病毒后代的数量)的异质性造成的,这取决于细胞寿命的分布和病毒粒子释放的机制。我们用“蚀相”阶段来分析病毒动力学模型:细胞被感染后但在其能够释放病毒粒子之前的一段时间。日食或随后的感染阶段的持续时间是非指数的,但由阶段组成。我们推导了这些病毒动力学模型的繁殖数的概率分布,并表明在感染细胞持续释放病毒的情况下,并且假设目标细胞过量,它是负二项分布。在确定性模型中,病毒感染的最终在宿主体内的建立或消灭完全取决于平均繁殖数是否分别大于或小于1。这里,灭绝的概率是由 R 的概率分布决定的,而不仅仅是其平均值。特别是,我们表明,在某些情况下,感染概率并不是平均繁殖数的增函数。
We consider stochastic models of individual infected cells. The reproduction number, R, is understood as a random variable representing the number of new cells infected by one initial infected cell in an otherwise susceptible (target cell) population. Variability in R results partly from heterogeneity in the viral burst size (the number of viral progeny generated from an infected cell during its lifetime), which depends on the distribution of cellular lifetimes and on the mechanism of virion release. We analyse viral dynamics models with an eclipse phase: the period of time after a cell is infected but before it is capable of releasing virions. The duration of the eclipse, or the subsequent infectious, phase is non-exponential, but composed of stages. We derive the probability distribution of the reproduction number for these viral dynamics models, and show it is a negative binomial distribution in the case of constant viral release from infectious cells, and under the assumption of an excess of target cells. In a deterministic model, the ultimate in-host establishment or extinction of the viral infection depends entirely on whether the mean reproduction number is greater than, or less than, one, respectively. Here, the probability of extinction is determined by the probability distribution of R, not simply its mean value. In particular, we show that in some cases the probability of infection is not an increasing function of the mean reproduction number.
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