Andino Raul, Domingo Esteban
Department of Microbiology and Immunology, University of California, San Francisco, USA.
Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
Virology. 2015 May;479-480:46-51. doi: 10.1016/j.virol.2015.03.022. Epub 2015 Mar 29.
New generation sequencing is greatly expanding the capacity to examine the composition of mutant spectra of viral quasispecies in infected cells and host organisms. Here we review recent progress in the understanding of quasispecies dynamics, notably the occurrence of intra-mutant spectrum interactions, and implications of fitness landscapes for virus adaptation and de-adaptation. Complementation or interference can be established among components of the same mutant spectrum, dependent on the mutational status of the ensemble. Replicative fitness relates to an optimal mutant spectrum that provides the molecular basis for phenotypic flexibility, with implications for antiviral therapy. The biological impact of viral fitness renders particularly relevant the capacity of new generation sequencing to establish viral fitness landscapes. Progress with experimental model systems is becoming an important asset to understand virus behavior in the more complex environments faced during natural infections.
新一代测序技术正在极大地扩展检测感染细胞和宿主生物中病毒准种突变谱组成的能力。在此,我们综述了在理解准种动态方面的最新进展,特别是突变谱内相互作用的发生,以及适应度景观对病毒适应和去适应的影响。同一突变谱的组分之间可建立互补或干扰,这取决于整体的突变状态。复制适应度与一个最优突变谱相关,该谱为表型灵活性提供分子基础,对抗病毒治疗具有启示意义。病毒适应度的生物学影响使得新一代测序技术建立病毒适应度景观的能力尤为重要。实验模型系统方面的进展正成为理解病毒在自然感染所面临的更复杂环境中的行为的一项重要资产。