论文标题
病毒种群中的抗原合作:宿主内病毒变体功能的转化
Antigenic cooperation in Viral Populations: Transformation of Functions of Intra-Host Viral Variants
论文作者
论文摘要
在本文中,我们通过抗原合作研究了宿主内病毒的适应 - 一种免疫逃生机制,可作为连续基因组多样化通过连续基因组多样化的逃生标准机制的一种替代方法,并允许解释与高度可突出病毒相关的许多实验观察结果。在这种机制中,跨免疫反应性网络的拓扑迫使宿主内病毒变体专注于互补作用,并适应宿主作为准社会生态系统的免疫反应。在这里,我们研究由进化和流行病学事件引起的免疫适应性的动态变化。首先,我们表明,具有改变抗原特征的病毒变体的出现可能会导致病毒生态系统的快速重新安排,并改变现有病毒变体所扮演的角色。特别是,它可能会将基因组多样化的免疫逃生的人口推向抗原合作适应的稳定状态。接下来,我们研究了两个长期感染的宿主之间病毒传播的影响,这导致在稳定的免疫适应平衡状态下合并了两个宿主内病毒群体。在这种情况下,我们还描述了新形成的病毒种群如何通过更改其成员的功能来适应宿主的环境。对于最小跨免疫反应性网络的分析,该结果是在分析上获得的,对于较大的人群而言。
In this paper we study intra-host viral adaptation by antigenic cooperation - a mechanism of immune escape that serves as an alternative to the standard mechanism of escape by continuous genomic diversification and allows to explain a number of experimental observations associated with the establishment of chronic infections by highly mutable viruses. Within this mechanism, the topology of a cross-immunoreactivity network forces intra-host viral variants to specialize for complementary roles and adapt to host's immune response as a quasi-social ecosystem. Here we study dynamical changes in immune adaptation caused by evolutionary and epidemiological events. First, we show that the emergence of a viral variant with altered antigenic features may result in a rapid re-arrangement of the viral ecosystem and a change in the roles played by existing viral variants. In particular, it may push the population under immune escape by genomic diversification towards the stable state of adaptation by antigenic cooperation. Next, we study the effect of a viral transmission between two chronically infected hosts, which results in merging of two intra-host viral populations in the state of stable immune-adapted equilibrium. In this case, we also describe how the newly formed viral population adapts to the host's environment by changing the functions of its members. The results are obtained analytically for minimal cross-immunoreactivity networks and numerically for larger populations.