Virus-immune dynamics determined by prey-predator interaction network and epistasis in viral fitness landscape
Virus-immune dynamics determined by prey-predator interaction network and epistasis in viral fitness landscape
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由猎物-捕食者相互作用网络和病毒适应性景观中的上位性决定的病毒-免疫动力学
DOI：
10.1007/s00285-022-01843-y
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发表时间：
2023
影响因子：
1.9
通讯作者：
Yahia, Fadoua
中科院分区：
文献类型：
--
作者：
Browne, Cameron J.;Yahia, Fadoua
种群动态和进化遗传学是生态系统结构的基础，在同一时间尺度上发生变化，相互作用的物种迅速更替，如病毒（如艾滋病毒）和免疫反应。因此，数学建模中的一个重要问题是将生态学、进化论和遗传学联系起来，这三个方面通常被分开处理。在这里，从布朗和史密斯的资源-猎物（消费者）-捕食者模型中的多个病毒和免疫反应群体的扩展分析，我们表明，病毒突变体在不同表位（免疫反应靶向的病毒蛋白质）的长期动态演变阻力由上位性在病毒适应度景观。特别是，持久的平衡病毒免疫（猎物捕食者）网络结构，如嵌套和一对一，和分叉的稳定性是由一个集合ofcircuits定义的组合病毒fitnesses是最低限度的添加剂内的一个超立方体的二进制序列表示所有可能的病毒表位序列根据immunodominancehierarchy排序。我们的常微分方程系统的数值解，沿着与一个扩展的随机版本，包括随机突变，展示了如何成对或乘法上位相互作用形状病毒进化对并发免疫反应和收敛到多变量的稳定状态的理论结果预测。此外，模拟说明了亚显性免疫应答的周期性输注如何诱导持久性病毒株的分叉，从而提供优于具有最强免疫应答的免疫疗法的替代策略的上级宿主结果。
Population dynamics and evolutionary genetics underly the structure of ecosystems, changing on the same timescale for interacting species with rapid turnover, such as virus (e.g. HIV) and immune response. Thus, an important problem in mathematical modeling is to connect ecology, evolution and genetics, which often have been treated separately. Here, extending analysis of multiple virus and immune response populations in a resource—prey (consumer)—predator model from Browne and Smith , we show that long term dynamics of viral mutants evolving resistance at distinct epitopes (viral proteins targeted by immune responses) are governed by epistasis in the virus fitness landscape. In particular, the stability of persistent equilibrium virus-immune (prey-predator) network structures, such as nested and one-to-one, and bifurcations are determined by a collection ofcircuitsdefined by combinations of viral fitnesses that are minimally additive within a hypercube of binary sequences representing all possible viral epitope sequences ordered according toimmunodominancehierarchy. Numerical solutions of our ordinary differential equation system, along with an extended stochastic version including random mutation, demonstrate how pairwise or multiplicative epistatic interactions shape viral evolution against concurrent immune responses and convergence to the multi-variant steady state predicted by theoretical results. Furthermore, simulations illustrate how periodic infusions of subdominant immune responses can induce a bifurcation in the persistent viral strains, offering superior host outcome over an alternative strategy of immunotherapy with strongest immune response.
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影响因子：
15.9
作者：
Liu, Michael K. P.;Hawkins, Natalie;Goonetilleke, Nilu
通讯作者：
Goonetilleke, Nilu
影响因子：
2
作者：
Champagnat, Nicolas;Meleard, Sylvie
通讯作者：
Meleard, Sylvie
影响因子：
4.3
作者：
Leviyang S;Ganusov VV
通讯作者：
Ganusov VV
复杂生态系统模型的部门稳定性
DOI：
--
发表时间：
1978
期刊：
影响因子：
--
作者：
B. Goh
通讯作者：
B. Goh
影响因子：
4.3
作者：
Ganusov VV;De Boer RJ
通讯作者：
De Boer RJ