Stern Adi, Yeh Ming Te, Zinger Tal, Smith Matt, Wright Caroline, Ling Guy, Nielsen Rasmus, Macadam Andrew, Andino Raul
Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Tel-Aviv 6997801, Israel.
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell. 2017 Mar 23;169(1):35-46.e19. doi: 10.1016/j.cell.2017.03.013.
Paralytic polio once afflicted almost half a million children each year. The attenuated oral polio vaccine (OPV) has enabled world-wide vaccination efforts, which resulted in nearly complete control of the disease. However, poliovirus eradication is hampered globally by epidemics of vaccine-derived polio. Here, we describe a combined theoretical and experimental strategy that describes the molecular events leading from OPV to virulent strains. We discover that similar evolutionary events occur in most epidemics. The mutations and the evolutionary trajectories driving these epidemics are replicated using a simple cell-based experimental setup where the rate of evolution is intentionally accelerated. Furthermore, mutations accumulating during epidemics increase the replication fitness of the virus in cell culture and increase virulence in an animal model. Our study uncovers the evolutionary strategies by which vaccine strains become pathogenic and provides a powerful framework for rational design of safer vaccine strains and for forecasting virulence of viruses. VIDEO ABSTRACT.
麻痹性脊髓灰质炎曾经每年折磨近50万儿童。减毒口服脊髓灰质炎疫苗（OPV）推动了全球范围的疫苗接种工作，几乎完全控制了这种疾病。然而，疫苗衍生脊髓灰质炎的流行在全球范围内阻碍了脊髓灰质炎病毒的根除。在此，我们描述了一种理论与实验相结合的策略，该策略描述了从OPV到强毒株的分子事件。我们发现大多数流行中都会发生类似的进化事件。利用一个简单的基于细胞的实验装置来复制驱动这些流行的突变和进化轨迹，在该装置中进化速率被有意加快。此外，流行期间积累的突变增加了病毒在细胞培养中的复制适应性，并增加了在动物模型中的毒力。我们的研究揭示了疫苗株变为致病性的进化策略，并为更安全疫苗株的合理设计以及预测病毒毒力提供了一个强大的框架。视频摘要。
