Multiple infection of cells changes the dynamics of basic viral evolutionary processes
Multiple infection of cells changes the dynamics of basic viral evolutionary processes
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细胞的多重感染改变了基本病毒进化过程的动态
DOI：
10.1002/evl3.95
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发表时间：
2019
影响因子：
5
通讯作者：
Komarova, Natalia L.
中科院分区：
文献类型：
--
作者：
Wodarz, Dominik;Levy, David N.;Komarova, Natalia L.
给定病毒的多个拷贝感染细胞可以以多种方式影响病毒进化，但一些最基本的进化动力学仍然没有得到充分研究。使用计算模型，我们调查感染的多样性如何影响固定概率的突变体，突变体的产生率，突变体入侵的时间。这些模型的一个重要见解是，对于中性和不利的表型，罕见的突变体最初在细胞多重感染的情况下享有适应性优势。这是因为多重感染允许罕见突变体进入更多的靶细胞并更快地传播，而它不会加速常驻野生型病毒的传播。罕见的突变群体可以通过进入未感染和野生型感染的细胞而增加，而建立的野生型群体最初只能通过进入未感染的细胞而生长。在这个最初的有利阶段之后，动态分别由漂移或负选择控制，并且较高的多样性降低了突变体在群体中固定的机会。因此，虽然感染多样性的增加在短期内促进了中性和不利突变体的存在，但从长远来看，这种可能性较小。我们展示了这些理论见解如何有助于解释低和高多重性下病毒进化的实验数据。这里探讨的动力学提供了一个基础，调查更复杂的病毒进化过程，包括重组，重配，以及互补/抑制相互作用。
The infection of cells by multiple copies of a given virus can impact viral evolution in a variety of ways, yet some of the most basic evolutionary dynamics remain underexplored. Using computational models, we investigate how infection multiplicity affects the fixation probability of mutants, the rate of mutant generation, and the timing of mutant invasion. An important insight from these models is that for neutral and disadvantageous phenotypes, rare mutants initially enjoy a fitness advantage in the presence of multiple infection of cells. This arises because multiple infection allows the rare mutant to enter more target cells and to spread faster, while it does not accelerate the spread of the resident wild-type virus. The rare mutant population can increase by entry into both uninfected and wild-type-infected cells, while the established wild-type population can initially only grow through entry into uninfected cells. Following this initial advantageous phase, the dynamics are governed by drift or negative selection, respectively, and a higher multiplicity reduces the chances that mutants fix in the population. Hence, while increased infection multiplicity promotes the presence of neutral and disadvantageous mutants in the short-term, it makes it less likely in the longer term. We show how these theoretical insights can be useful for the interpretation of experimental data on virus evolution at low and high multiplicities. The dynamics explored here provide a basis for the investigation of more complex viral evolutionary processes, including recombination, reassortment, as well as complementary/inhibitory interactions.
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