Quasispecies and the implications for virus persistence and escape

Esteban Domingo
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引用次数: 70

Abstract

Background: In the 1970s Manfred Eigen and colleagues proposed a new model of molecular evolution to explain adaptability and rapid evolution of simple replicons, as those that probably populated the earth at the onset of life. This model of evolution placed emphasis on mutant generation, to the point of invalidating the concept of wild-type genomes as a defined sequence of nucleotides. In striking similarity with the proposals for such early replicons, present-day RNA viruses consist of complex distributions of nonidentical but closely related genomes termed quasispecies.

Objectives: To discuss indeterminations inherent to a quasispecies structure and to the analytical procedures to define it, biological implications of quasispecies, and the need to take into account this type of population structure, in order to design effective strategies to prevent and control diseases caused by highly variable viruses.

Results: Quasispecies have many biological implications, extending from viral pathogenesis to the emergence of new pathogens, rapid antigenic variation, and alterations in cell tropism, virulence, host range and viral gene expression.

Conclusions: Diseases caused by highly variable RNA viruses prove very difficult to control and vaccine development against such viruses are largely unsuccessful. It is important to understand quasispecies composition and dynamics, as quasispecies are an important step in the natural history of RNA viruses.

准物种及其对病毒持久性和逃逸的影响
背景:在20世纪70年代,Manfred Eigen和他的同事提出了一个新的分子进化模型来解释简单复制子的适应性和快速进化,因为这些复制子可能在生命开始时就遍布地球。这种进化模型强调突变体的产生,以至于使野生型基因组作为一个确定的核苷酸序列的概念失效。与这些早期复制子的建议惊人地相似,今天的RNA病毒由称为准种的不相同但密切相关的基因组的复杂分布组成。目标:讨论准物种结构和确定准物种的分析程序所固有的不确定性、准物种的生物学含义,以及考虑到这类种群结构的必要性,以便设计有效的战略,预防和控制由高度可变的病毒引起的疾病。结果:准物种具有许多生物学意义,从病毒的发病机制到新病原体的出现,抗原的快速变异,以及细胞趋向性、毒力、宿主范围和病毒基因表达的改变。结论:由高度可变的RNA病毒引起的疾病很难控制,针对这类病毒的疫苗开发基本上是不成功的。了解准种的组成和动态是很重要的,因为准种是RNA病毒自然史上重要的一步。
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