Laboratory of Nematology, Wageningen University, 6708 PB Wageningen, The Netherlands.
Laboratory of Virology, Wageningen University, 6708 PB Wageningen, The Netherlands.
Viruses. 2017 Sep 30;9(10):284. doi: 10.3390/v9100284.
Viral susceptibility and disease progression is determined by host genetic variation that underlies individual differences. Genetic polymorphisms that affect the phenotype upon infection have been well-studied for only a few viruses, such as HIV-1 and Hepatitis C virus. However, even for well-studied viruses the genetic basis of individual susceptibility differences remains elusive. Investigating the effect of causal polymorphisms in humans is complicated, because genetic methods to detect rare or small-effect polymorphisms are limited and genetic manipulation is not possible in human populations. Model organisms have proven a powerful experimental platform to identify and characterize polymorphisms that underlie natural variations in viral susceptibility using quantitative genetic tools. We summarize and compare the genetic tools available in three main model organisms, , , and , and illustrate how these tools can be applied to detect polymorphisms that determine the viral susceptibility. Finally, we analyse how candidate polymorphisms from model organisms can be used to shed light on the underlying mechanism of individual variation. Insights in causal polymorphisms and mechanisms underlying individual differences in viral susceptibility in model organisms likely provide a better understanding in humans.
病毒易感性和疾病进展由宿主遗传变异决定，这些变异导致了个体差异。虽然已经很好地研究了影响感染后表型的少数几种病毒（如 HIV-1 和丙型肝炎病毒）的遗传多态性，但即使是对于研究得很好的病毒，个体易感性差异的遗传基础仍然难以捉摸。在人类中研究因果多态性的影响很复杂，因为检测罕见或小效应多态性的遗传方法有限，并且在人类群体中不可能进行遗传操作。模式生物已被证明是一种强大的实验平台，可以使用定量遗传工具来识别和表征导致病毒易感性自然变异的多态性。我们总结并比较了三种主要模式生物、、和中的可用遗传工具，并说明了如何将这些工具应用于检测决定病毒易感性的多态性。最后，我们分析了如何利用模型生物中的候选多态性来阐明个体差异的潜在机制。了解模型生物中病毒易感性的因果多态性和个体差异的潜在机制，可能会更好地理解人类。
