Increased burst size in multiply infected cells can alter basic virus dynamics
Increased burst size in multiply infected cells can alter basic virus dynamics
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DOI：
10.1186/1745-6150-7-16
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发表时间：
2012-05-08
期刊：
影响因子：
5.5
通讯作者：
Wodarz, Dominik
中科院分区：
文献类型：
--
作者：
Cummings, Kara W.;Levy, David N.;Wodarz, Dominik
背景：病毒感染的动态已经在各种环境下通过实验和数学模型进行了广泛的研究。大多数数学模型都假设一次只有一种病毒可以感染给定的细胞。然而，很明显，特别是在高病毒载量的情况下，细胞可能会被多个病毒副本感染，这一过程称为共感染。这一点在人类免疫缺陷病毒 (HIV) 的实验中得到了最好的证明，尽管人们认为它与许多其他病毒感染同样相关。在先前探索的数学模型中，受感染细胞的病毒输出并不取决于细胞中的病毒数量，即病毒复制受到细胞因素而不是病毒因素的限制。在这种情况下，基本的病毒动力学特性不会因共感染而改变。结果：在这里，我们探索了另一种假设，即倍增感染细胞的特征是爆发大小增加，并发现这可以从根本上改变模型预测。在这种情况下，感染的建立可能不仅仅取决于病毒的基本繁殖率，而可能取决于初始病毒载量。感染后，病毒数量不需要呈直线指数增长。相反，随着病毒载量变大，指数增长率会随着时间的推移而增加。此外，该模型表明，抗病毒药物抑制病毒种群的能力可能取决于治疗开始时的病毒载量。这是因为更多的共感染细胞产生更多的病毒，且病毒载量更高。因此，耐药性的程度不仅取决于病毒基因型，还取决于共感染细胞的流行程度。结论：我们的工作表明，多重感染细胞中增加的爆发大小如何改变基本的感染动态。这构成了未来对模型假设和预测进行实验测试的基础，可以区分不同的场景。
Background: The dynamics of viral infections have been studied extensively in a variety of settings, both experimentally and with mathematical models. The majority of mathematical models assumes that only one virus can infect a given cell at a time. It is, however, clear that especially in the context of high viral load, cells can become infected with multiple copies of a virus, a process called coinfection. This has been best demonstrated experimentally for human immunodeficiency virus (HIV), although it is thought to be equally relevant for a number of other viral infections. In a previously explored mathematical model, the viral output from an infected cell does not depend on the number of viruses that reside in the cell, i.e. viral replication is limited by cellular rather than viral factors. In this case, basic virus dynamics properties are not altered by coinfection.Results: Here, we explore the alternative assumption that multiply infected cells are characterized by an increased burst size and find that this can fundamentally alter model predictions. Under this scenario, establishment of infection may not be solely determined by the basic reproductive ratio of the virus, but can depend on the initial virus load. Upon infection, the virus population need not follow straight exponential growth. Instead, the exponential rate of growth can increase over time as virus load becomes larger. Moreover, the model suggests that the ability of anti-viral drugs to suppress the virus population can depend on the virus load upon initiation of therapy. This is because more coinfected cells, which produce more virus, are present at higher virus loads. Hence, the degree of drug resistance is not only determined by the viral genotype, but also by the prevalence of coinfected cells.Conclusions: Our work shows how an increased burst size in multiply infected cells can alter basic infection dynamics. This forms the basis for future experimental testing of model assumptions and predictions that can distinguish between the different scenarios.